Stefan Agewall

• Ni, Wenli; Agewall, Stefan; Benson, Lina; Breitner, Susanne; Nobile, Federica & Savarese, Gianluigi [Show all 8 contributors for this article] (2026). Cold Spells, Heat Waves, and Nonoptimal Air Temperature and Risk of Heart Failure Hospitalization in Sweden. Journal of the American College of Cardiology. ISSN 0735-1097. 88(9), p. 1016–1029. doi: 10.1016/j.jacc.2026.07.008. Full text in Research Archive
• Tamargo, Juan; Agewall, Stefan; Ambrosio, Giuseppe; Borghi, Claudio; Cerbai, Elisabetta & Dan, Gheorghe A [Show all 18 contributors for this article] (2026). Cardiovascular pharmacotherapy in 2025. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 12(3), p. 166–166. doi: 10.1093/ehjcvp/pvag016. Full text in Research Archive Show summary

  Abstract Despite recent advances in cardiovascular pharmacotherapy, prevention and treatment of many cardiovascular diseases remain limited with a clear need for more effective and safer pharmacological strategies. Here, we summarize the most relevant advances in cardiovascular pharmacotherapy in 2025, including the approval of four new drugs (aficamten, etripamil, lerodalcibep, and plozasiran), the label expansions for five already approved drugs, and the results of major randomized clinical trials with already approved drugs, including those that met the prespecified primary endpoints (positive trials) representing new pharmacological options for cardiovascular diseases, those with neutral or negative results, which did not confirm the primary endpoints and the withdrawal from the US market of Andexanet-alfa for safety concerns. Finally, we present the most promising experimental cardiovascular drugs currently being investigated in ongoing Phase 2 and 3 clinical trials.

• Ni, Wenli; Stafoggia, Massimo; Zhang, Siqi; Ljungman, Petter; Breitner, Susanne & Bont, Jeroen de [Show all 10 contributors for this article] (2025). Short-term exposure to ambient temperature variability and myocardial infarction hospital admissions: A nationwide case-crossover study in Sweden. PLoS Medicine. ISSN 1549-1277. 22(5). doi: 10.1371/journal.pmed.1004607. Full text in Research Archive Show summary

  Background Climate change threatens human health and general welfare via multiple dimensions. However, the associations of short-term exposure to temperature variability, a crucial aspect of climate change, with myocardial infarction (MI) hospital admissions remains unclear. Methods and findings This population-based nationwide study employed a time-stratified, case-crossover design to investigate the association between ambient temperature variability and MI hospital admissions among 233,617 patients recorded in the SWEDEHEART registry in Sweden between 2005 and 2019. High-resolution (1 × 1 km) daily mean ambient temperature was assigned to patients’ residential areas. Temperature variability was calculated as the difference between the same-day (as the MI event) ambient temperature and the average temperature over the preceding 7 days. An upward temperature shift represents a rise in the current day’s temperature relative to the 7-day average, while a downward temperature shift indicates a corresponding decrease. A conditional logistic regression model with distributed lag non-linear model was applied to estimate the association between ambient temperature variability and total MI (encompassing all MI types), ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) hospital admissions at lag 0–6 days. Potential effect modifiers, such as sex, history of diseases, and season, were also examined. The patients had an average age of 70.6 years, and 34.5% of them were female. Our study found that an upward temperature shift was associated with increased risks of total MI (encompassing all MI types), STEMI, and NSTEMI hospital admissions at lag 0 day, with odds ratios (OR, 95% confidence intervals [CIs]) of 1.009 (1.005, 1.013; p < 0.001), 1.014 (1.006, 1.022; p < 0.001), and 1.007 (1.001, 1.012; p = 0.014) per 1 °C increase, respectively. These associations attenuated and became non-significant over lags 1–6 days. Furthermore, a downward temperature shift was associated with increased risks of hospital admissions for total MI (encompassing all MI types) at a lag of 2 days with an OR (95% CI): 1.003 (1.001, 1.005; p = 0.014), and for STEMI at lags 2 and 3 days with ORs (95% CI): 1.006 (1.002, 1.010; p = 0.001) and 1.005 (1.001, 1.008; p = 0.011), per 1 °C decrease, respectively. Conversely, higher downward temperature shifts were associated with decreased risks of total MI (encompassing all MI types) and NSTEMI at lag 0 day. No significant associations were observed at other lag days for downward temperature shifts. Males and patients with diabetes had higher MI hospitalization risks from upward temperature shift exposure, while downward temperature shift exposure in cold seasons posed greater MI hospitalization risks. A methodological limitation was the use of ambient temperature variability as a proxy for personal exposure, which, while practical for large-scale studies, may not precisely reflect individual temperature exposure. Conclusions This nationwide study contributes insights that short-term exposures to higher temperature variability—greater upward or downward temperature shifts—are associated with an increased risk of MI hospitalization. Our finding highlights the cardiovascular health threats posed by higher temperature variability, which are anticipated to increase in frequency and intensity due to climate change.

• Sandner, Sigrid; Gaudino, Mario; Agewall, Stefan; Bonalumi, Giorgia; Bonaros, Nikolaos & Czerny, Martin [Show all 16 contributors for this article] (2025). Antithrombotic therapy after coronary artery bypass graft surgery: a Clinical Consensus Statement of the ESC Working Group on Cardiovascular Surgery, the ESC Working Group on Cardiovascular Pharmacotherapy, and the European Association for Cardio-Thoracic Surgery (EACTS). European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 67(8). doi: 10.1093/ejcts/ezaf243. Full text in Research Archive
• Ni, Wenli; Benson, Lina; Ljungman, Petter; Nobile, Federica; Breitner, Susanne & Zhang, Siqi [Show all 11 contributors for this article] (2025). Short-Term Exposure to Low and High Temperatures and Mortality Among Patients With Heart Failure in Sweden. JAMA cardiology. ISSN 2380-6583. 10(12), p. 1276–1284. doi: 10.1001/jamacardio.2025.3932. Full text in Research Archive
• Winnberg, Oscar; Brolin, Elin; Y-Hassan, Shams; Henareh, Loghman; Sörensson, Peder & Collste, Olov [Show all 23 contributors for this article] (2025). Incremental value of coronary computed tomography angiography in addition to invasive coronary angiography in MINOCA. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 41(6), p. 1151–1160. doi: 10.1007/s10554-025-03401-1. Full text in Research Archive Show summary

  Patients with the working diagnosis myocardial infarction with nonobstructive coronary arteries (MINOCA) have diverse underlying causes warranting further investigations. Despite the documented superiority of coronary computed tomography angiography (CCTA) over invasive coronary angiography (ICA) in plaque detection, the former is not routinely recommended for MINOCA patients, highlighting a knowledge gap regarding CCTA’s incremental value. The objective of this study is to assess the prevalence and extent of coronary atherosclerosis in MINOCA patients using CCTA, and to evaluate the incremental value of CCTA over ICA alone in detecting coronary atherosclerosis. The data from 163 MINOCA patients who underwent both CCTA and ICA in two prospective studies were retrospectively analyzed to compare the occurrence and distribution of coronary atherosclerotic plaques detected with ICA versus CCTA, evaluating CCTA’s incremental value. CCTA detected coronary atherosclerosis in 48% of subjects; ICA did so in 47%. Notable disagreement, reflected by kappa values of 0.34 (95% confidence interval [CI] 0.19–0.48) across all segments and 0.41 (95% CI 0.27–0.55) for proximal segments (both p < 0.0001), highlighted discrepancies between CCTA and ICA in the detection of atherosclerosis presence and location. Combining CCTA with ICA provided significant incremental value in detecting atherosclerosis in coronary segments (p < 0.001). MINOCA patients frequently exhibit non-obstructive coronary plaques. Agreement between CCTA and ICA is poor. CCTA provides valuable additional information on atherosclerotic segments. Therefore, CCTA should be recognized as a complementary tool to ICA, aiding risk assessment and treatment decisions in the context of MINOCA.

• Winnberg, Oscar; Jensen, Jens; Y-Hassan, Shams; Henareh, Loghman; Sörensson, Peder & Collste, Olov [Show all 22 contributors for this article] (2025). Association of myocardial bridging and LAD length with Takotsubo syndrome: A MINOCA cross-sectional study. International Journal of Cardiology. ISSN 0167-5273. 443. doi: 10.1016/j.ijcard.2025.133950. Full text in Research Archive Show summary

  Background Takotsubo syndrome (TTS) is an acute cardiac condition triggered by emotional or physical stress, characterized by a catecholamine surge and transient left ventricular dysfunction. Although myocardial bridging (MB) and left anterior descending artery (LAD) length have been proposed as contributing factors, their roles in TTS remain uncertain. This study aimed to assess whether TTS is associated with MB or LAD length in a well-characterized myocardial infarction with non-obstructive coronary arteries (MINOCA) cohort. Methods We analyzed 183 participants from the prospective Stockholm Myocardial Infarction with Normal Coronaries (SMINC) 1 and 2 studies, which focused on MINOCA. All participants underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA). MB was assessed with CCTA, and LAD length was measured using ICA. TTS patients (n = 60) were compared with MINOCA controls without TTS (n = 123). Results MB was present in 37 % of TTS patients and 42 % of controls, with no significant association observed (p = 0.523), including when stratified by partial or full encasement. LAD length did not differ significantly between groups (p = 0.088). Conclusion This study found no significant association between MB or LAD length and the occurrence of TTS. These results suggest that structural variations in the LAD are unlikely to play a major role in the development of TTS, underscoring the importance of exploring alternative pathophysiological mechanisms beyond coronary anatomy.

• Tamargo, Juan; Agewall, Stefan; Ambrosio, Giuseppe; Borghi, Claudio; Cerbai, Elisabetta & Dan, Gheorghe A. [Show all 18 contributors for this article] (2025). New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2024. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 11(3), p. 292–317. doi: 10.1093/ehjcvp/pvaf012. Full text in Research Archive Show summary

  Despite substantial advances in cardiovascular pharmacotherapy and devices in recent years, prevention and treatment of many cardiovascular diseases (CVDs) remain limited, thus reflecting the need for more effective and safer pharmacological strategies. In this review, we summarize the most relevant studies in cardiovascular pharmacotherapy in 2024, including the approval of first-in-class drugs for the treatment of resistant hypertension and pulmonary arterial hypertension, label expansions for bempedoic acid and semaglutide, and the results of major randomized clinical trials (RCTs) that have met the pre-specified primary endpoints, thereby filling some gaps in knowledge and opening new perspectives in the management of CVD, and those RCTs whose results did not confirm the proposed research hypotheses. We also include a section on drug safety, where we describe the newest data on adverse reactions and drug–drug interactions that may complicate treatment and/or reduce drug adherence with the consequent decrease in drug effectiveness. Finally, we present the most important ongoing phase 2 and phase 3 clinical trials assessing the efficacy and safety of cardiovascular drugs for the prevention and treatment of CVD.

• Atar, Dan; Vandenbriele, Christophe; Agewall, Stefan; Gigante, Bruna; Goette, Andreas & Gorog, Diana A. [Show all 13 contributors for this article] (2025). Management of patients with congenital bleeding disorders and cardiac indications for antithrombotic therapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 11(3), p. 275–289. doi: 10.1093/ehjcvp/pvaf006. Full text in Research Archive Show summary

  Aims Cardiologists have only had rare exposure to haemophilia patients and patients with other congenital bleeding disorders during the last decades, as these patients had a reduced life expectancy and were partly protected against thrombosis due to the bleeding disorder. With the availability of effective and safe replacement therapies of clotting factors, the average life expectancy in these populations of patients has significantly increased, and thrombotic complications may occur. Methods and results The European Society of Cardiology Working Group on Thrombosis has taken the initiative to broaden the spectrum of these haematological conditions to include patients with a larger variety of congenital bleeding disorders with concomitant cardiac conditions as compared to a recent position paper by the European Haematology Association in collaboration with other societies (ISTH, European Association for Haemophilia and Allied Disorders, and ESO). Management of antithrombotic therapy or thromboprophylaxis in these individuals is challenging due to the wide phenotypes encompassed by congenital bleeding disorders. These include abnormalities in both primary haemostasis (involving von Willebrand factor and platelet function) and secondary haemostasis (related to coagulation factors and fibrinogen). Bleeding disorders range from mild to very severe. Based on existing literature, we provide clinical consensus statements on optimizing antithrombotic treatment strategies for patients with congenital bleeding disorders and highlight the current gaps in knowledge in these complex clinical settings. Conclusion Of importance, an individualized approach to antithrombotic therapy is warranted to properly balance the two risks of thrombosis and bleeding. Adoption of the safest interventional techniques, reduction of the intensity and/or duration of antithrombotic therapies, and attention to the safe levels of clotting factors is generally advised.

• Singh, Nidhi; Areal, Ashtyn Tracy; Breitner, Susanne; Zhang, Siqi; Agewall, Stefan & Schikowski, Tamara [Show all 7 contributors for this article] (2024). Heat and Cardiovascular Mortality: An Epidemiological Perspective. Circulation Research. ISSN 0009-7330. 134(9), p. 1098–1112. doi: 10.1161/CIRCRESAHA.123.323615. Full text in Research Archive Show summary

  As global temperatures rise, extreme heat events are projected to become more frequent and intense. Extreme heat causes a wide range of health effects, including an overall increase in morbidity and mortality. It is important to note that while there is sufficient epidemiological evidence for heat-related increases in all-cause mortality, evidence on the association between heat and cause-specific deaths such as cardiovascular disease (CVD) mortality (and its more specific causes) is limited, with inconsistent findings. Existing systematic reviews and meta-analyses of epidemiological studies on heat and CVD mortality have summarized the available evidence. However, the target audience of such reviews is mainly limited to the specific field of environmental epidemiology. This overarching perspective aims to provide health professionals with a comprehensive overview of recent epidemiological evidence of how extreme heat is associated with CVD mortality. The rationale behind this broad perspective is that a better understanding of the effect of extreme heat on CVD mortality will help CVD health professionals optimize their plans to adapt to the changes brought about by climate change and heat events. To policymakers, this perspective would help formulate targeted mitigation, strengthen early warning systems, and develop better adaptation strategies. Despite the heterogeneity in evidence worldwide, due in part to different climatic conditions and population dynamics, there is a clear link between heat and CVD mortality. The risk has often been found to be higher in vulnerable subgroups, including older people, people with preexisting conditions, and the socioeconomically deprived. This perspective also highlights the lack of evidence from low- and middle-income countries and focuses on cause-specific CVD deaths. In addition, the perspective highlights the temporal changes in heat-related CVD deaths as well as the interactive effect of heat with other environmental factors and the potential biological pathways. Importantly, these various aspects of epidemiological studies have never been fully investigated and, therefore, the true extent of the impact of heat on CVD deaths remains largely unknown. Furthermore, this perspective also highlights the research gaps in epidemiological studies and the potential solutions to generate more robust evidence on the future consequences of heat on CVD deaths.

• Tornvall, Per; Beltrame, John F.; Nickander, Jannike; Sörensson, Peder; Reynolds, Harmony R. & Agewall, Stefan (2024). How to Use Cardiac Magnetic Resonance Imaging in Myocardial Infarction with Nonobstructive Coronary Arteries. Circulation Cardiovascular Imaging. ISSN 1941-9651. 17(7), p. e016463–e016463. doi: 10.1161/CIRCIMAGING.123.016463. Full text in Research Archive
• Ni, Wenli; Stafoggia, Massimo; Zhang, Siqi; Ljungman, Petter; Breitner, Susanne & Bont, Jeroen de [Show all 10 contributors for this article] (2024). Short-Term Effects of Lower Air Temperature and Cold Spells on Myocardial Infarction Hospitalizations in Sweden. Journal of the American College of Cardiology. ISSN 0735-1097. 84(13), p. 1149–1159. doi: 10.1016/j.jacc.2024.07.006. Full text in Research Archive
• Tamargo, Juan; Agewall, Stefan; Borghi, Claudio; Ceconi, Claudio; Cerbai, Elisabetta & Dan, Gheorghe A [Show all 16 contributors for this article] (2024). New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(3), p. 219–244. doi: 10.1093/ehjcvp/pvae013. Full text in Research Archive
• Xiong, Wei; Agewall, Stefan & Yamashita, Yugo (2024). Anticoagulation in cancer-associated thrombosis: how long should the therapy be? European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(1), p. 3–4. doi: 10.1093/ehjcvp/pvad075. Full text in Research Archive
• Frühwald, Lisa; Fasching, Peter; Dobrev, Dobromir; Kaski, Juan Carlos; Borghi, Claudio & Wassmann, Sven [Show all 10 contributors for this article] (2024). Management of dyslipidaemia in patients with comorbidities—facing the challenge: Value and limitations of lipid-lowering drugs in liver disease Effects/Interactions of lipid-lowering agents on/with the liver. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 11(2), p. 164–173. doi: 10.1093/ehjcvp/pvae095. Full text in Research Archive
• Gigante, Bruna; Tamargo, Juan; Agewall, Stefan; Atar, Dan; Berg, Jurrien ten & Campo, Gianluca [Show all 18 contributors for this article] (2024). Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(7), p. 614–645. doi: 10.1093/ehjcvp/pvae064. Full text in Research Archive
• Haller, Paul M.; Kazem, Niema; Agewall, Stefan; Borghi, Claudio; Ceconi, Claudio & Dobrev, Dobromir [Show all 19 contributors for this article] (2024). Oral anticoagulation in patients with left ventricular thrombus: a systematic review and meta-analysis. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(5), p. 444–453. doi: 10.1093/ehjcvp/pvae042. Full text in Research Archive
• Tschiderer, Lena; Seekircher, Lisa; Izzo, Raffaele; Mancusi, Costantino; Manzi, Maria V. & Baldassarre, Damiano [Show all 63 contributors for this article] (2023). Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies. Journal of the American Heart Association (JAHA). 12(12), p. e027657–e027657. doi: 10.1161/JAHA.122.027657. Full text in Research Archive Show summary

  Background The association between common carotid artery intima‐media thickness (CCA‐IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA‐IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta‐analysis of 20 prospective studies from the Proof‐ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA‐IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA‐IMT was 0.71 mm (SD, 0.17 mm). Over a median follow‐up of 5.9 years (5th–95th percentile, 1.9–19.0 years), 8278 individuals developed first‐ever carotid plaque. We combined study‐specific odds ratios (ORs) for incident carotid plaque using random‐effects meta‐analysis. Baseline CCA‐IMT was approximately log‐linearly associated with the odds of developing carotid plaque. The age‐, sex‐, and trial arm–adjusted OR for carotid plaque per SD higher baseline CCA‐IMT was 1.40 (95% CI, 1.31–1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low‐ and high‐density lipoprotein cholesterol, and lipid‐lowering and antihypertensive medication was 1.34 (95% CI, 1.24–1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29–1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large‐scale individual participant data meta‐analysis demonstrated that CCA‐IMT is associated with the long‐term risk of developing first‐ever carotid plaque, independent of traditional cardiovascular risk factors.

• Berg, Emma; Agewall, Stefan; Brolin, Elin B.; Caidahl, Kenneth; Cederlund, Kerstin & Collste, Olov [Show all 16 contributors for this article] (2023). Health-related quality-of-life up to one year after myocardial infarction with non-obstructive coronary arteries. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. 9(6), p. 639–644. doi: 10.1093/ehjqcco/qcac072. Full text in Research Archive Show summary

  Abstract Aims Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) are a heterogenous group and previous studies indicate a decreased Health-related quality-of-life (HRQoL) compared with patients with myocardial infarction with obstructive coronary artery disease and healthy individuals. However, longitudinal data are scarce. Therefore, the aim was to explore HRQoL among patients with MINOCA during a one-year period after the acute event in comparison with a group of healthy individuals and to describe HRQoL in patients with Takotsubo Syndrome (TTS). Methods and results Patients with MINOCA were recruited from five hospitals in the Stockholm region (SMINC-2 study, clinical trials: NCT2318498). Patients responded to the HRQoL questionnaire RAND-36 between days 2–4, after 6 and 12 months respectively. A sample of population-based individuals was used as a comparison group. A total of 142 MINOCA patients, (70% women) mean age of 56 years, responded. A population-based sample of 317 volunteers (66% women) mean age of 57 years. Patients with MINOCA scored lower than the comparison group in the domains role functioning physical, social functioning, and role functioning emotional (P = 0.01–0.02) at 12 months. In these domains of HRQoL there was no improvement in MINOCA patients during 12 months follow-up. In the domains of energy/fatigue vitality and emotional well-being the scores improved and were similar to the comparison group at 12 months. Patients with TTS scored generally lower on RAND-36 than MINOCA patients without TTS. Conclusion Physical, social, and emotional functioning did not improve during the first year after MINOCA, indicating a need for increased follow-up including psychological support.

• Martínez-Montesinos, Lorena; Rivera-Caravaca, José Miguel; Agewall, Stefan; Soler, Eva; Lip, Gregory Y.H. & Marín, Francisco [Show all 7 contributors for this article] (2023). Polypharmacy and adverse events in atrial fibrillation: Main cause or reflection of multimorbidity? Biomedicine & Pharmacotherapy. ISSN 0753-3322. 158. doi: 10.1016/j.biopha.2022.114064. Full text in Research Archive Show summary

  Background Previous evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a ‘real-world’ cohort of AF patients starting vitamin K antagonists (VKAs). Methods Prospective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥ 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded. Results 1050 patients (51.5 % females, median age 77 [69–83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11–2.03), hypertension (OR 2.53; 95 % CI 1.51–4.22), diabetes (OR 3.11; 95 % CI 2.31–4.17), vascular disease (OR 3.08; 95 % CI 2.19–4.33), heart failure (OR 1.86; 95 % CI 1.35–2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9–3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07–2.92), and composite thrombotic/thromboembolic events (HR 1.55, 95 % CI 1.05–2.31). Conclusion In this “real world” AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events.

• Drexel, Heinz; Saely, Christoph H. & Agewall, Stefan (2023). Fibrates: one more lost paradise in lipid treatment. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(2), p. 121–121. doi: 10.1093/ehjcvp/pvac072. Full text in Research Archive
• Seekircher, Lisa; Tschiderer, Lena; Lind, Lars; Safarova, Maya S; Kavousi, Maryam & Ikram, M. Arfan [Show all 39 contributors for this article] (2023). Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment. European Heart Journal Open (EHJ Open). 3(5). doi: 10.1093/ehjopen/oead089. Full text in Research Archive Show summary

  Aims Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: −0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39–0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14–1.22; I² = 30.7%) and 1.20 (1.18–1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07–1.12; I² = 8.4%) and 1.14 (1.12–1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

• Drexel, Heinz; Tamargo, Juan; Kaski, Juan Carlos; Lewis, Basil S.; Saely, Christoph H. & Fraunberger, Peter [Show all 11 contributors for this article] (2023). Triglycerides revisited: is hypertriglyceridaemia a necessary therapeutic target in cardiovascular disease? European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(6), p. 570–582. doi: 10.1093/ehjcvp/pvad044. Full text in Research Archive
• Tjessem, Lars Holm & Agewall, Stefan (2023). EVALUATION OF A STRUCTURALIZED SICK-LEAVE PROGRAMME COMPARED WITH USUAL CARE SICK-LEAVE MANAGEMENT FOR PATIENTS AFTER AN ACUTE MYOCARDIAL INFARCTION. Journal of Rehabilitation Medicine. ISSN 1650-1977. 55. doi: 10.2340/jrm.v55.4569. Full text in Research Archive Show summary

  Objective: To compare a structuralized sick-leave programme with usual care sick-leave management in patients after an acute myocardial infarction. We hypothesize that a structured sick-leave programme will yield a faster return to work without negatively affecting quality of life.Methods: Patients admitted to Oslo University Hospital due to an acute myocardial infarction were included in the study. Patients were randomized into an intervention group or a conventional care group. Patients randomized to the intervention group were provided with a standard programme with full-time sick leave for 2 weeks after discharge and then encouraged to return to work. The sick leave of the conventional group was mainly managed by their general practitioner.Results: A total of 143 patients were included in the study. The conventional care group had a mean of 20.4 days absent from work, while that of the intervention group was significantly lower, with a mean of 17.2 days (p &lt; 0.001) absent. There was no significant change in quality of life between the groups.Conclusion: These findings strengthen the case for structuralized follow-up of patients with acute myocardial infarction, as this will have positive economic consequences for the patient and society as a whole, without making quality of life worse. Further investigation, with a larger study population, is warranted to determine the extent of health benefits conferred by early return to work. LAY ABSTRACTThis study aimed to compare a structuralized sick-leave programme with usual care sick-leave management in patients after an acute myocardial infarction. The study included 143 patients who were admitted to Oslo University Hospital due to an acute myocardial infarction. Patients were randomized to an intervention group or a conventional care group. The intervention group followed a standard programme with full-time sick leave for 2 weeks after discharge, and were then encouraged to return to work. Intervention group patients had access to a telephone number to contact a cardiologist for advice if needed. The sick leave of the conventional group was mainly managed by their general practitioner. The sick leave of the intervention group was, 3.2 days shorter, whereas there was no difference in quality of life between the groups. In conclusion, these results indicate potentially large positive economic consequences of a structuralized sick-leave programme for patients and for society as a whole, with no worsening in quality of life.

• Wärme, Jonatan; Sundqvist, Martin O.; Hjort, Marcus; Agewall, Stefan; Collste, Olov & Ekenbäck, Christina [Show all 16 contributors for this article] (2023). Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease. International Journal of Molecular Sciences. ISSN 1661-6596. 24(18). doi: 10.3390/ijms241814143. Full text in Research Archive Show summary

  Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

• Fröhlich, Hanna; Bossmeyer, Anna; Kazmi, Syed; Goode, Kevin M.; Agewall, Stefan & Atar, Dan [Show all 12 contributors for this article] (2023). Glycaemic control and insulin therapy are significant confounders of the obesity paradox in patients with heart failure and diabetes mellitus. Clinical Research in Cardiology. ISSN 1861-0684. doi: 10.1007/s00392-023-02268-3. Full text in Research Archive Show summary

  Background: A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown. Methods: We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated. Results: We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%. Conclusion: In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker. Keywords: Diabetes mellitus; Heart failure; Mortality; Obesity paradox; Reverse epidemiology. © 2023. The Author(s).

• Tamargo, Juan; Agewall, Stefan; Borghi, Claudio; Ceconi, Claudio; Cerbai, Elisabetta & Dan, Gheorghe A. [Show all 15 contributors for this article] (2023). New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(4), p. 353–370. doi: 10.1093/ehjcvp/pvad034. Full text in Research Archive
• Nguyen, Thao; Fagerland, Morten; Hollan, Ivana; Whist, Jon Elling; Feinberg, Mark W. & Agewall, Stefan (2023). High-sensitivity cardiac troponin T is associated with disease activity in patients with inflammatory arthritis. PLOS ONE. 18:e0281155.(2), p. 1–10. doi: 10.1371/journal.pone.0281155. Full text in Research Archive Show summary

  Objective: To investigate whether high-sensitivity cardiac troponin T (hsTnT) correlates to markers of disease activity in inflammatory arthritis (IA), and whether antirheumatic treatment influences hsTnT levels. Methods: We assessed 115 patients with active IA (64 rheumatoid arthritis (RA), 31 psoriatic arthritis and 20 ankylosing spondylitis) before and after using methotrexate (MTX) alone or tumor necrosis factor inhibitor (TNFi) with or without MTX co-medication (TNFi±MTX). All patients starting with TNFi had been previously unsuccessfully treated with MTX monotherapy. HsTnT (measured in serum by electro-chemiluminescence immunoassay (Roche Elecsys® Troponin T- high-sensitivity)), and other clinical and laboratory parameters were evaluated at baseline, and after 6 weeks and 6 months of treatment. Results: Of markers of disease activity, baseline levels of hsTnT positively correlated with Physicians' Global Assessment Score of disease activity in the total patient cohort (p = 0.039). In RA group, hsTnT positively correlated with swollen joints, Disease Activity Score for 28 joints with ESR and serum tumor necrosis factor levels (p = 0.025, p = 0.008, p = 0.01, respectively). Median hsTnT at baseline was 5.0 ng/L, and did not change significantly at 6-week visit (6.0 ng/L, p = 0.37) and 6-month visit (6.0 ng/L, p = 0.18) with either antirheumatic therapy. Conclusions: HsTnT levels were associated with inflammatory markers for IA disease activity. However, while inflammatory markers significantly improved after antirheumatic treatment, hsTnT did not change during the 6-month follow-up period. Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

• Komiyama, Maki; Agewall, Stefan & Hasegawa, Koji (2022). Future of antithrombotic therapy for heart failure with coronary artery disease. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. doi: 10.1093/ehjcvp/pvac030. Full text in Research Archive
• Tamargo, Juan; Kjeldsen, Keld Per; Delpon, Eva; Semb, Anne Grete; Cerbai, Elisabetta & Dobrev, Dobromir [Show all 19 contributors for this article] (2022). Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(4), p. 406–419. doi: 10.1093/ehjcvp/pvac005. Full text in Research Archive
• Drexel, Heinz; Pocock, Stuart J; Lewis, Basil S; Saely, Christoph H; Kaski, Juan Carlos & Rosano, Giuseppe M. C [Show all 19 contributors for this article] (2022). Subgroup analyses in randomized clinical trials: value and limitations. Review #3 on important aspects of randomized clinical trials in cardiovascular pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(3), p. 302–310. doi: 10.1093/ehjcvp/pvab048. Full text in Research Archive
• Tamargo, Juan; Kaski, Juan Carlos; Kimura, Takeshi; Barton, Jack Charles; Yamamoto, Ko & Komiyama, Maki [Show all 10 contributors for this article] (2022). Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(7), p. 738–751. doi: 10.1093/ehjcvp/pvac040. Full text in Research Archive
• Hall, Trygve Sørdahl; Ørn, Stein; Zannad, Faiez; Rossignol, Patrick; Duarte, Kevin & Solomon, Scott D. [Show all 10 contributors for this article] (2022). The Association of Smoking with Hospitalization and Mortality Differs According to Sex in Patients with Heart Failure Following Myocardial Infarction. Journal of Women's Health. ISSN 1540-9996. 31(3), p. 310–320. doi: 10.1089/jwh.2021.0326. Full text in Research Archive
• Hokstad, Ingrid; Greco, Daniela; Deyab, Gia; Fagerland, Morten; Agewall, Stefan & Hjeltnes, Gunnbjørg [Show all 10 contributors for this article] (2022). Effects of Antirheumatic Treatment on Cell Cholesterol Efflux and Loading Capacity of Serum Lipoproteins in Spondylarthropathies. Journal of Clinical Medicine. 11(24). doi: 10.3390/jcm11247330. Full text in Research Archive Show summary

  Spondyloarthropathies (SpA) are associated with increased cardiovascular risk. Among possible mechanisms is the dysfunction of serum lipoproteins in regulating cell cholesterol homeostasis. Cholesterol efflux capacity (CEC)—the atheroprotective ability of HDL (high density lipoproteins) to accept cholesterol from macrophages—might predict cardiovascular disease independently of HDL-cholesterol levels. We aimed at evaluating modifications of CEC and of the atherogenic cholesterol loading capacity (CLC) of serum lipoproteins in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) following anti-rheumatic treatment. A total of 62 SpA patients (37 PsA and 25 AS) were evaluated before and after treatment with tumor necrosis factor inhibitor and/or methotrexate. CEC and CLC were measured by radioisotopic and fluorometric techniques, respectively. Endothelial function was assessed by finger plethysmography (Endopat). In the whole SpA group, total and HDL-cholesterol increased after treatment, while lipoprotein(a) decreased and CLC was unchanged. Treatment was associated with increased Scavenger Receptor class B type I (SR-BI)-mediated CEC in the AS group. SR-BI- and ABCG1-mediated CEC were negatively associated with inflammatory parameters and positively related to coffee consumption. SR-BI CEC and CLC were positively and negatively associated with endothelial function, respectively. Our pilot study suggests that anti-rheumatic treatment is associated with favorable modulation of lipoprotein quality and function in SpA, particularly in AS, in spite of the induced increase in total cholesterol levels. If confirmed in a larger population, this might represent an atheroprotective benefit beyond what is reflected by conventional serum lipid profile. Keywords: spondyloarthropathies; psoriatic arthritis; anchylosing spondylitis; psoriatic arthritis; anti-rheumatic treatment; lipoproteins; high density lipoprotein; low density lipoprotein; cell cholesterol efflux; macrophages

• Magavern, Emma F.; Kaski, Juan Carlos; Turner, Richard M.; Drexel, Heinz; Janmohamed, Azara & Scourfield, Andrew [Show all 21 contributors for this article] (2022). Challenges in cardiovascular pharmacogenomics implementation: A viewpoint from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(1), p. 100–103. doi: 10.1093/ehjcvp/pvab063. Full text in Research Archive
• Nguyen, Thao; Hokstad, Ingrid; Fagerland, Morten; Mollnes, Tom Eirik; Hollan, Ivana & Feinberg, Mark W. [Show all 10 contributors for this article] (2022). Antirheumatic therapy is associated with reduced complement activation in rheumatoid arthritis. PLOS ONE. 17 (2), p. 1–18. doi: 10.1371/journal.pone.0264628. Full text in Research Archive Show summary

  Background The complement system plays an important role in pathophysiology of cardiovascular disease (CVD), and might be involved in accelerated atherogenesis in rheumatoid arthritis (RA). The role of complement activation in response to treatment, and in development of premature CVD in RA, is limited. Therefore, we examined the effects of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) on complement activation using soluble terminal complement complex (TCC) levels in RA; and assessed associations between TCC and inflammatory and cardiovascular biomarkers. Methods We assessed 64 RA patients starting with MTX monotherapy (n = 34) or TNFi with or without MTX co-medication (TNFi±MTX, n = 30). ELISA was used to measure TCC in EDTA plasma. The patients were examined at baseline, after 6 weeks and 6 months of treatment. Results Median TCC was 1.10 CAU/mL, and 57 (89%) patients had TCC above the estimated upper reference limit (<0.70). Compared to baseline, TCC levels were significantly lower at 6-week visit (0.85 CAU/mL, p<0.0001), without significant differences between the two treatment regimens. Notably, sustained reduction in TCC was only achieved after 6 months on TNFi±MTX (0.80 CAU/mL, p = 0.006). Reductions in TCC after treatment were related to decreased C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin 6, and increased levels of total, high and low-density lipoprotein cholesterol. Similarly, baseline TCC was significantly related to baseline CRP, ESR and interleukin 6. Patients with endothelial dysfunction had higher baseline TCC than those without (median 1.4 versus 1.0 CAU/mL, p = 0.023). Conclusions Patients with active RA had elevated TCC, indicating increased complement activation. TCC decreased with antirheumatic treatment already after 6 weeks. However, only treatment with TNFi±MTX led to sustained reduction in TCC during the 6-month follow-up period. RA patients with endothelial dysfunction had higher baseline TCC compared to those without, possibly reflecting involvement of complement in the atherosclerotic process in RA.

• Magavern, Emma Forton; Kaski, Juan Carlos; Turner, Richard M.; Drexel, Heinz; Janmohamed, Azara & Scourfield, Andrew [Show all 21 contributors for this article] (2022). The role of pharmacogenomics in contemporary cardiovascular therapy: A position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(1), p. 85–99. doi: 10.1093/ehjcvp/pvab018. Full text in Research Archive
• Hadidi, Seif El; Rosano, Giuseppe; Tamargo, Juan; Agewall, Stefan; Drexel, Heinz & Kaski, Juan Carlos [Show all 10 contributors for this article] (2022). Potentially inappropriate prescriptions in heart failure with reduced ejection fraction: ESC position statement on heart failure with reduced ejection fraction-specific inappropriate prescribing. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(2), p. 187–210. doi: 10.1093/ehjcvp/pvaa108. Full text in Research Archive
• Nguyen, Thao; Fagerland, Morten; Deyab, Gia; Hjeltnes, Gunnbjørg; Hollan, Ivana & Feinberg, Mark W. [Show all 9 contributors for this article] (2021). Antirheumatic therapy is not associated with changes in circulating N-terminal pro-brain natriuretic peptide levels in patients with autoimmune arthritis. PLOS ONE. 16:e0253793(6), p. 1–17. doi: 10.1371/journal.pone.0253793. Full text in Research Archive Show summary

  Background: Patients with autoimmune arthritis (AA) are at increased risk for impaired cardiac function and heart failure. This may be partly due to the effect of inflammation in heart function. The impact of antirheumatic drugs on cardiac dysfunction in AA remains controversial. Therefore, we aimed to examine effects of antirheumatic treatment on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in AA patients and its relationship to inflammatory markers. Methods: We examined 115 patients with AA (64 rheumatoid arthritis (RA), 31 psoriatic arthritis and 20 ankylosis spondylitis) starting with methotrexate (MTX) monotherapy or tumor necrosis factor inhibitors (TNFi) with or without MTX co-medication. NT-proBNP (measured in serum by ECLIA from Roche Diagnostics), and other clinical and laboratory parameters were evaluated at baseline, after 6 weeks and 6 months of treatment. Results: NT-proBNP levels did not change significantly after 6 weeks and 6 months of antirheumatic therapy (pbaseline-6weeks = 0.939; pbaseline-6months = 0.485), although there was a modest improvement from 6 weeks to 6 months in the MTX only treatment group (median difference = -18.2 [95% CI = -32.3 to -4.06], p = 0.013). There was no difference in the effects of MTX monotherapy and TNFi regimen on NT-proBNP levels. The changes in NT-proBNP after antirheumatic treatment positively correlated with changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Baseline NT-proBNP levels were related to baseline CRP and ESR levels, and some other established markers of disease activities in crude analyses. Conclusion: Circulating levels of NT-proBNP were related to established inflammatory markers at baseline, and the changes in NT-proBNP after antirheumatic treatment were positively related to these markers. Nevertheless, antirheumatic therapy did not seem to affect NT-proBNP levels compared to baseline, even though inflammatory markers significantly improved.

• Krogager, Maria Lukács; Kragholm, Kristian; Thomassen, Jesper Qvist; Søgaard, Peter; Lewis, Basil S & Wassmann, Sven [Show all 19 contributors for this article] (2021). Update on management of hypokalaemia and goals for the lower potassium level in patients with cardiovascular disease: A review in collaboration with the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(6), p. 557–567. doi: 10.1093/ehjcvp/pvab038. Full text in Research Archive
• Y-Hassan, Shams; Sörensson, Peder; Ekenbäck, Christina; Lundin, Magnus; Agewall, Stefan & Brolin, Elin Bacsovics [Show all 20 contributors for this article] (2021). Plasma catecholamine levels in the acute and subacute stages of takotsubo syndrome: Results from the Stockholm myocardial infarction with normal coronaries 2 study. Clinical Cardiology. ISSN 0160-9289. doi: 10.1002/clc.23723. Full text in Research Archive Show summary

  Aims It is well-accepted that takotsubo syndrome (TS) is characterized by a massive surge of plasma catecholamines despite lack of solid evidence. The objective of this study was to examine the hypothesis of a massive catecholamine elevation in TS by studying plasma-free catecholamine metabolites in patients participating in the Stockholm myocardial infarction (MI) with normal coronaries 2 (SMINC-2) study where TS constituted more than one third of the patients. Methods and results The patients included in the SMINC-2 study were classified, according to cardiac magnetic resonance (CMR) imaging findings (148 patients), which was performed at a median of 3 days after hospital admission. Plasma-free catecholamine metabolites; metanephrine, normetanephrine, and methoxy-tyramine were measured on day 2–4 after admission. Catecholamine metabolite levels were available in 125 patients. One hundred and ten (88%) of the 125 patients included in SMINC-2 study, and 38 (86.4%) of the 44 patients with TS had completely normal plasma metanephrine and normetanephrine levels. All patients had normal plasma methoxy-tyramine levels. Fourteen (11.2%) of the 125 patients included in SMINC-2 study, and 5 (11.6%) of the 43 patients with TS had mild elevations (approximately 1.2 times the upper normal limits) of either plasma metanephrine or normetanephrine. One patient with pheochromocytoma-triggered TS had marked elevation of plasma metanephrine and mild elevation of plasma normetanephrine. There were no significant differences between the number or degree of catecholamine metabolite elevations between the different groups of patients with CMR imaging diagnosis included in SMINC-2 study. Conclusion There was no evidence of massive catecholamine elevations in the acute and subacute stages of TS apart from one patient with pheochromocytoma-induced TS. Most of the TS patients had normal catecholamine metabolites indicating that blood-borne catecholamines do not play a direct role in the pathogenesis of TS.

• Täger, Tobias; Frankenstein, Lutz; Atar, Dan; Agewall, Stefan; Frey, Norbert & Grundtvig, Morten [Show all 9 contributors for this article] (2021). Influence of receptor selectivity on benefits from SGLT2 inhibitors in patients with heart failure: a systematic review and head-to-head comparative efficacy network meta-analysis. Clinical Research in Cardiology. ISSN 1861-0684. doi: 10.1007/s00392-021-01913-z. Full text in Research Archive Show summary

  Background: Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon. Methods: We identified randomized controlled trials investigating the use of SGLT2i in patients with HF-either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression. Results: We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted. Conclusion: Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes. Keywords: Diabetes mellitus; Heart failure; Outcome; Receptor selectivity; Sodium glucose cotransporter 2 inhibitor. © 2021. The Author(s).

• Tamargo, Juan & Agewall, Stefan (2021). Fluoroquinolone use and valvular heart disease: Is the jury still out? European Heart Journal. ISSN 0195-668X. 42(30), p. 2909–2911. doi: 10.1093/eurheartj/ehab426. Full text in Research Archive
• Svenungsson, Elisabet; Spaak, Jonas; Strandberg, Karin; Wallén, Håkan N.; Agewall, Stefan & Brolin, Elin B. [Show all 17 contributors for this article] (2021). Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries. Journal of Internal Medicine. ISSN 0954-6820. doi: 10.1111/joim.13409. Full text in Research Archive Show summary

  Background Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). Objectives To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C–protein C inhibitor (APC–PCI) complex. Methods Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case–control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β2glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC–PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. Results Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β2glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC–PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. Conclusions aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability—measured by increased levels of the APC–PCI complex—were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

• Sörensson, Peder; Ekenbäck, Christina; Lundin, Magnus; Agewall, Stefan; Brolin, Elin Bacsovics & Caidahl, Kenneth [Show all 20 contributors for this article] (2021). Early Comprehensive Cardiovascular Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries. JACC Cardiovascular Imaging. ISSN 1936-878X. 14(9), p. 1774–1783. doi: 10.1016/j.jcmg.2021.02.021. Full text in Research Archive Show summary

  Objectives The objective of the SMINC-2 (Stockholm Myocardial Infarction With Normal Coronaries 2) study was to determine if more than 70% of patients with myocardial infarction with nonobstructed coronary arteries (MINOCA), investigated early with comprehensive cardiovascular magnetic resonance (CMR), could receive a diagnosis entirely by imaging. Background The etiology of MINOCA is heterogeneous, including coronary, cardiac, and noncardiac causes. Patients with MINOCA, therefore, represent a diagnostic challenge where CMR is increasingly used. Methods The SMINC-2 study was a prospective study of 148 patients with MINOCA imaged with 1.5-T CMR with T1 and extracellular volume mapping early after hospital admission, compared to 150 patients with MINOCA imaged using 1.5-T CMR without mapping techniques from the SMINC-1 study as historic controls. Results CMR was performed at a median of 3 (SMINC-2) versus 12 (SMINC-1) days after hospital admission. In total, 77% of patients received a diagnosis with CMR imaging in the SMINC-2 study compared to 47% in the SMINC-1 study (p < 0.001). Compared to SMINC-1, CMR in SMINC-2 detected higher proportions of myocarditis (17% vs. 7%; p = 0.01) and takotsubo syndrome (35% vs. 19%; p = 0.002) but similar proportions of myocardial infarction (22% vs. 19%; p = 0.56) and other cardiomyopathies (3% vs. 2%; p = 0.46). Conclusions The results of the SMINC-2 study show that 77% of all patients with MINOCA received a diagnosis when imaged early with CMR, including advanced tissue characterization, which was a considerable improvement in comparison to the SMINC-1 study. This supports the use of early CMR imaging as a diagnostic tool in the investigation of patients with MINOCA. (Stockholm Myocardial Infarction With Normal Coronaries [SMINC]-2 Study on Diagnosis Made by Cardiac MRI [SCMINC-2]; NCT02318498)

• Deyab, Gia; Reine, Trine M.; Vuong, Tram Thu; Jenssen, Trond Geir; Hjeltnes, Gunnbjørg & Agewall, Stefan [Show all 11 contributors for this article] (2021). Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis. PLOS ONE. 16(7), p. e0253247–e0253247. doi: 10.1371/journal.pone.0253247. Full text in Research Archive Show summary

  The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.

• Drexel, Heinz; Lewis, Basil S.; Rosano, Giuseppe M. C.; Saely, Christoph H.; Tautermann, Gerda & Huber, Kurt [Show all 18 contributors for this article] (2021). The age of randomized clinical trials: Three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid, diabetes, and antithrombotic trials. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(5), p. 453–459. doi: 10.1093/ehjcvp/pvaa126. Full text in Research Archive
• Tschiderer, Lena; Seekircher, Lisa; Klingenschmid, Gerhard; Izzo, Raffaele; Baldassarre, Damiano & Iglseder, Bernhard [Show all 63 contributors for this article] (2020). The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale. Gerontology. ISSN 0304-324X. 66(5), p. 447–459. doi: 10.1159/000508498. Full text in Research Archive
• Knuuti, Juhani; Wijns, William; Saraste, Antti; Capodanno, Davide; Barbato, Emanuele & Funck-Brentano, Christian [Show all 25 contributors for this article] (2020). 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. European Heart Journal. ISSN 0195-668X. 41(3), p. 407–477. doi: 10.1093/eurheartj/ehz425. Full text in Research Archive
• Willeit, Peter; Tschiderer, Lena; Allara, Elias; Reuber, Kathrin; Seekircher, Lisa & Gao, Lu [Show all 76 contributors for this article] (2020). Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk : Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients. Circulation. ISSN 0009-7322. 142(7), p. 621–642. doi: 10.1161/CIRCULATIONAHA.120.046361. Full text in Research Archive Show summary

  Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

• Savarese, Gianluigi; Reiner, Martin F; Uijl, Alicia; D'Amario, Domenico; Agewall, Stefan & Atar, Dan [Show all 23 contributors for this article] (2020). Antithrombotic therapy and major adverse limb events in patients with chronic lower extremity arterial disease: systematic review and meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(2), p. 86–93. doi: 10.1093/ehjcvp/pvz036. Full text in Research Archive Show summary

  Abstract Aims The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of antithrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. Methods and results Study inclusion criteria were: enrolment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single-antiplatelet therapy (SAPT); dual-antiplatelet therapy vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30 447 patients were included. Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization [relative risk (RR) 0.89, 95% confidence interval (CI) 0.83–0.94] and limb amputation (RR 0.63, 95% CI 0.46–0.86), as well as stroke (RR 0.82, 95% CI 0.70–0.97). There was no statistically significant effect on the risk of myocardial infarction (RR 0.98, 95% CI 0.87–1.11), all-cause (RR 0.93, 95% CI 0.86–1.01), and cardiovascular death (RR 0.97, 95% CI 0.86–1.08). Risk of major bleeding increased (RR 1.23, 95% CI 1.04–1.44). Conclusion In patients with LEAD, more intense antithrombotic therapy reduces the risk of limb amputation and revascularization as well as stroke with an increase in the risk of bleeding events.

• Täger, Tobias; Atar, Dan; Agewall, Stefan; Katus, Hugo A.; Grundtvig, Morten & Cleland, John G.F. [Show all 9 contributors for this article] (2020). Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Heart Failure Reviews. ISSN 1382-4147. p. 1–15. doi: 10.1007/s10741-020-09954-8. Full text in Research Archive Show summary

  Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of < 52 weeks confirmed the main results. Similar results were obtained when restricting mortality analyses to patients included in cardiovascular outcome trials (n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results. Keywords Sodium-glucose cotransporter-2 inhibitors . Type 2 diabetes . Mortality . Heart failure . Efficacy

• Lewis, Basil S.; Agewall, Stefan & Rosano, Giuseppe (2020). MSc in clinical trials: a new flagship Working Group project. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(5), p. 284–284. doi: 10.1093/ehjcvp/pvaa078. Full text in Research Archive
• Bahls, Martin; Lorenz, Matthias W.; Dörr, Marcus; Gao, Lu; Kitagawa, Kazuo & Tuomainen, Tomi-Pekka [Show all 55 contributors for this article] (2020). Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 27(3), p. 234–243. doi: 10.1177/2047487319877078. Full text in Research Archive Show summary

  <i>Aims</i> - Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.<p> <p><i>Methods and results</i> - An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.<p> <p><i>Conclusion</i> - Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

• Drexel, Heinz; Rosano, Giuseppe; Lewis, Basil S.; Huber, Kurt; Vonbank, Alexander & Dopheide, Jörn F [Show all 11 contributors for this article] (2020). The age of randomized clinical trials: Three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid and diabetes trials. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(2), p. 97–103. doi: 10.1093/ehjcvp/pvz029. Full text in Research Archive Show summary

  Abstract Randomized clinical trials (RCTs) are important and the Gold Standard for drugs in modern cardiovascular (CV) therapy. The cornerstone of RCTs is the recording of hard clinical endpoints instead of surrogates. It is important to select an appropriate endpoint. Efficacy endpoints must be clinically relevant and can be hierarchically divided. A very interesting innovation in endpoint acquisition is the total event paradigm.

• Hokstad, Ingrid; Deyab, Gia; Fagerland, Morten; Lyberg, Torstein; Hjeltnes, Gunnbjørg & Førre, Øystein Thorleiv [Show all 9 contributors for this article] (2019). Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study. PLOS ONE. 14(7), p. 1–16. doi: 10.1371/journal.pone.0220079. Full text in Research Archive Show summary

  Background The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers. Methods From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis factor (TNF) inhibitor alone (n = 25), combined with methotrexate (MTX) (n = 10), or MTX monotherapy (n = 16). Complement activation was determined by the soluble terminal complement complex (sC5b-9), inflammation by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and endothelial function by finger plethysmography (Endopat) at baseline, after 6 weeks and 6 months of treatment. Results SpA patients had sC5b-9 levels at (PsA) or above (AS) the upper limit of the estimated reference range. Median sC5b-9 levels decreased significantly from baseline to 6 weeks, with no significant difference between the AS and PsA group. Notably, a significant reduction in sC5b-9 was observed after administration of TNF inhibitor ± MTX, whereas no significant changes were observed in patients treated with MTX alone. Between 6 weeks and 6 months, sC5b-9 remained stable across all subgroups. Reduction in sC5b-9 was independently related to decreased ESR and CRP, and to increased high density cholesterol and total cholesterol. Reduction in sC5b-9 from baseline to 6 weeks was associated with improved EF in age and gender adjusted analyses. Conclusion TNF-inhibition, but not MTX monotherapy, led to rapid and sustained reduction of complement activation in SpA. Thus, the observed decrease in cardiovascular morbidity in patients treated with TNF-inhibitors might be partly due to its beneficial effect on complement. Trial registration Clinical Trials (NCT00902005), retrospectively registered on the 14th of May 2009.

• Hjort, Marcus; Eggers, Kai M.; Lindhagen, Lars; Agewall, Stefan; Brolin, Elin B. & Collste, Olov [Show all 17 contributors for this article] (2019). Increased inflammatory activity in patients 3 months after myocardial infarction with nonobstructive coronary arteries. Clinical Chemistry. ISSN 0009-9147. 65(8), p. 1023–1030. doi: 10.1373/clinchem.2018.301085. Full text in Research Archive
• Rosano, Giuseppe M.C.; Spoletini, Ilaria & Agewall, Stefan (2019). Pharmacology of new treatments for hyperkalaemia: Patiromer and sodium zirconium cyclosilicate. European Heart Journal, Supplement. ISSN 1520-765X. 21, p. A28–A33. doi: 10.1093/eurheartj/suy035. Full text in Research Archive Show summary

  Hyperkalaemia is a life-threatening condition, resulting from decreased renal function or dysfunctional homoeostatic mechanisms, often affecting patients with cardiovascular (CV) disease. Drugs such as renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in CV patients but can also cause drug-induced hyperkalaemia. New therapeutic options exist to enhance potassium excretion in these patients. To this aim, we reviewed pharmacological properties and available data on patiromer and sodium zirconium cyclosilicate for the treatment of hyperkalaemia. These agents have been shown in randomized trials to significantly reduce serum potassium in patients with hyperkalaemia on renin-angiotensin-aldosterone system inhibitors. Additional research should focus on their long-term effects/safety profiles and drug–drug interactions.

• Täger, Tobias; Fröhlich, Hanna; Grundtvig, Morten; Seiz, Mirjam; Schellberg, Dieter & Goode, Kevin [Show all 14 contributors for this article] (2019). Comparative effectiveness of loop diuretics on mortality in the treatment of patients with chronic heart failure – A multicenter propensity score matched analysis. International Journal of Cardiology. ISSN 0167-5273. 289, p. 83–90. doi: 10.1016/j.ijcard.2019.01.109. Full text in Research Archive Show summary

  Background: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. Methods: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. Results: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31–1.73, p b 0.001, and HR 1.34, CI 1.18–1.52, p b 0.001, respectively). Mortality was higher in bumetanide users when compared to furosemide users (HR 1.11, 95% CI 1.02–1.20, p = 0.01). However, there was no significant association between loop diuretic choice and all-cause mortality in any of the matched samples (bumetanide vs. furosemide, HR 1.03, 95% CI 0.93–1.14, p = 0.53; bumetanide vs. torasemide, HR 0.98, 95% CI 0.78–1.24, p = 0.89; furosemide vs. torasemide, HR 1.02, 95% CI 0.84–1.24, p = 0.82). The results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HF, rhythm, and systolic blood pressure. Conclusions: In patients with HF, mortality is not affected by the choice of individual loop diuretics.

• Rosano, Giuseppe M.C.; Spoletini, Ilaria; Vitale, Cristina & Agewall, Stefan (2019). Hyperkalemia and Renin–Angiotensin–Aldosterone System Inhibitors Dose Therapy in Heart Failure With Reduced Ejection Fraction. Cardiac failure review. ISSN 2057-7540. 5(3), p. 130–132. doi: 10.15420/cfr.2019.8.2. Full text in Research Archive Show summary

  Renin–angiotensin–aldosterone system inhibitors (RAASi) are known to improve outcomes in patients who have heart failure with reduced ejection fraction (HFrEF). To reduce mortality in these patients, RAASi should be uptitrated to the maximally tolerated dose. However, RAASi may also cause hyperkalemia. As a result of this side-effect, doses of RAASi are reduced, discontinued and seldom reinstated. Thus, the therapeutic target needed in these patients is often not reached because of hyperkalemia. Also, submaximal dosing of RAASi may be a result of symptomatic hypotension, syncope, hypoperfusion, reduced kidney function and other factors. The reduction of RAASi dose leads to adverse outcomes, such as an increased risk of mortality. Management of these side-effects is pivotal to maximise the use of RAASi in HFrEF, particularly in high-risk patients.

• Hausvater, Anais; Pasupathy, Sivabaskari; Tornvall, Per; Gandhi, Himali; Tavella, Rosanna & Beltrame, John [Show all 12 contributors for this article] (2019). ST-segment elevation and cardiac magnetic resonance imaging findings in myocardial infarction with non-obstructive coronary arteries. International Journal of Cardiology. ISSN 0167-5273. 287, p. 128–131. doi: 10.1016/j.ijcard.2019.04.028. Full text in Research Archive
• Hollan, Ivana; Ronda, Nicoletta; Dessein, Patrick; Agewall, Stefan; Karpouzas, George & Tamargo, Juan [Show all 12 contributors for this article] (2019). Lipid management in rheumatoid arthritis: a position paper by the Cardiovascular Pharmacotherapy Working Group of European Society of Cardiology. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(2), p. 104–114. doi: 10.1093/ehjcvp/pvz033. Full text in Research Archive
• Fröhlich, Hanna; Rosenfeld, Nitzan; Täger, Tobias; Goode, Kevin; Kazmi, Syed & Hole, Torstein [Show all 13 contributors for this article] (2019). Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe. Heart. ISSN 1355-6037. 105(16), p. 1252–1259. doi: 10.1136/heartjnl-2018-314256. Full text in Research Archive
• Sulzgruber, Patrick; Wassmann, Sven; Semb, Anne Grete; Doehner, Wolfram; Widimský, Petr & Gremmel, Thomas [Show all 19 contributors for this article] (2019). Oral anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1: a current opinion of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and European Society of Cardiology Council on Stroke. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(3), p. 171–180. doi: 10.1093/ehjcvp/pvz016. Full text in Research Archive Show summary

  Oral anticoagulation in patients presenting with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1 (CHA2DS2-VASc of 2 in women) remains a challenging approach in clinical practice. Therapeutic decisions need to balance the individual benefit of reducing thromboembolic risk against the potential harm due to an increase in bleeding risk in this intermediate risk patient population. Within the current opinion statement of the European Society of Cardiology working group of cardiovascular pharmacotherapy and the European Society of Cardiology council on stroke the currently available evidence on the anti-thrombotic management in patients presenting with a CHA2DS2-VASc of 1 is summarized. Easily applicable tools for a personalized refinement of the individual thromboembolic risk in patients with atrial fibrillation and a CHA2DS2-VASc score of 1 that guide clinicians through the question whether to anticoagulate or not are provided.

• Navarese, Eliano Pio; Andreotti, Felicita; Raggi, Paolo; Kolodziejczak, Michalina; Buffon, Antonino & Bliden, Kevin [Show all 13 contributors for this article] (2019). Baseline low-density lipoprotein cholesterol to predict the extent of cardiovascular benefit from lipid-lowering therapies: a review. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(1), p. 47–54. doi: 10.1093/ehjcvp/pvy038. Full text in Research Archive Show summary

  Lipid-lowering therapies have been shown to improve cardiovascular outcome in a wide range of patients. The current guidelines recommend a graded approach to reduction in low-density lipoprotein cholesterol (LDL-C) proportional to the patient’s risk, with the goal of achieving either a certain magnitude of reduction or a specific threshold of final LDL-C. Recent findings from a meta-analysis of numerous randomized trials suggest that more attention should be given to the baseline LDL-C of an individual patient. In this review, we discuss how the baseline LDL-C level may provide a means to better understand the results of recent cardiovascular outcome trials and the expected benefits of lipid-lowering therapies. The exact quantification of the clinical benefit associate with an intensified lipid-lowering therapy depends on the baseline LDL-C. Mortality is reduced in a log-linear fashion only when LDL-C > 100 mg/dL.

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• Agewall, Stefan (2023). Atrial fibrillation has gone from a boring disease to a very hot condition. Why is that? European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(5), p. 401–402. doi: 10.1093/ehjcvp/pvad049. Full text in Research Archive
• Agewall, Stefan (2023). Focus on prevention in diabetes mellitus and lipid disorder. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(4), p. 295–296. doi: 10.1093/ehjcvp/pvad037. Full text in Research Archive
• Agewall, Stefan (2023). A tailor-made suit always fits best. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(3), p. 199–200. doi: 10.1093/ehjcvp/pvad024. Full text in Research Archive
• Agewall, Stefan (2023). Cardiovascular preventive actions. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(6), p. 497–498. doi: 10.1093/ehjcvp/pvad054. Full text in Research Archive
• Aunan, Kristin; Atar, Dan & Agewall, Stefan (2023). Klima - en hjertesak. Hjerteforum. ISSN 0802-1465. 1, p. 54–61. Full text in Research Archive
• Agewall, Stefan (2023). Focus on lipid treatment. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(2), p. 119–120. doi: 10.1093/ehjcvp/pvad007. Full text in Research Archive
• Agewall, Stefan (2022). Pharmacological treatment of CVD. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 9(1), p. 1–3. doi: 10.1093/ehjcvp/pvac068. Full text in Research Archive
• Agewall, Stefan (2022). Treating patients with anticoagulants and antiplatelet drugs is always a balance between risk for thrombosis vs. risk for bleeding. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(7), p. 645–647. doi: 10.1093/ehjcvp/pvac048. Full text in Research Archive
• Agewall, Stefan (2022). New cardiology aspects of triple antithrombotic therapy, diabetes without insulin therapy as a risk factor in atrial fibrillation, treatment of gout, cholesterol lowering treatment, prostate cancer treatment, out-of-hospital cardiac arrest, Fabry disease, beta-blocker use after myocardial infarction in patients with normal ejection fraction, cardio-renal benefits of SGLT2 Inhibitors and interpretation of clinical trials. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(3), p. 213–215. doi: 10.1093/ehjcvp/pvac019. Full text in Research Archive
• Agewall, Stefan (2022). To treat or not to treat. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(8), p. 754–755. doi: 10.1093/ehjcvp/pvac062. Full text in Research Archive
• Agewall, Stefan (2022). Future of European Heart Journal Cardiovascular Pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(8), p. 753–753. doi: 10.1093/ehjcvp/pvac061. Full text in Research Archive
• Agewall, Stefan (2022). Focus on optimizing treatment of coronary heart disease. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(5), p. 431–433. doi: 10.1093/ehjcvp/pvac039. Full text in Research Archive
• Agewall, Stefan (2022). Focus on different aspects of atrial fibrillation. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(4), p. 323–324. doi: 10.1093/ehjcvp/pvac035. Full text in Research Archive
• Agewall, Stefan (2022). Prevention is still the key to success. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(6), p. 537–538. doi: 10.1093/ehjcvp/pvac046. Full text in Research Archive
• Tamargo, Juan; Hasegawa, Koji & Agewall, Stefan (2022). Toward personalized medicine for cardiovascular pharmacotherapy. European Heart Journal. ISSN 0195-668X. 43(45), p. 4719–4721. doi: 10.1093/eurheartj/ehac413. Full text in Research Archive
• Agewall, Stefan (2022). Optimizing individual heart failure treatment. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(2), p. 105–107. doi: 10.1093/ehjcvp/pvab087. Full text in Research Archive
• Agewall, Stefan (2022). Treatment with dual antiplatelet therapy after an acute coronary event may often be tailor-made for the patient. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 8(1), p. 1–3. doi: 10.1093/ehjcvp/pvab078. Full text in Research Archive
• Agewall, Stefan (2021). Different aspects of giving the optimal antiplatelet treatment. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(3), p. 169–170. doi: 10.1093/ehjcvp/pvab037. Full text in Research Archive
• Agewall, Stefan (2021). More knowledge about atrial fibrillation, still we need to learn. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(5), p. 361–362. doi: 10.1093/ehjcvp/pvab067. Full text in Research Archive
• Agewall, Stefan (2021). Unsolved pharmacological issues with cardiology. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(6), p. 461–462. doi: 10.1093/ehjcvp/pvab077. Full text in Research Archive
• Agewall, Stefan (2021). Adherence to pharmacological treatment: How can we improve? European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(4), p. 261–262. doi: 10.1093/ehjcvp/pvab049. Full text in Research Archive
• Agewall, Stefan (2021). Atrial fibrillation in registries. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(1), p. 1–2. doi: 10.1093/ehjcvp/pvaa142. Full text in Research Archive
• Agewall, Stefan (2021). Antiplatelet treatment in coronary syndrome. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(2), p. 81–82. doi: 10.1093/ehjcvp/pvab015. Full text in Research Archive
• Agewall, Stefan (2020). Focus on subpopulations of atrial fibrillation patients. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(3), p. 131–132. doi: 10.1093/ehjcvp/pvaa034. Full text in Research Archive
• Agewall, Stefan (2020). Focus on blood pressure and risk factor intervention. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(6), p. 339–340. doi: 10.1093/ehjcvp/pvaa130. Full text in Research Archive
• Hall, Trygve Sørdahl; Orn, S; Zanned, F.; Rossignol, Patrick; Duarte, K. & Solomon, S. [Show all 10 contributors for this article] (2020). The association of smoking to cardiovascular death differs according to age and sex following myocardial infarction complicated by heart failure or left ventricular dysfunction. Full text in Research Archive
• Agewall, Stefan (2020). Lipids and antithrombotic treatment. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(2), p. 71–71. doi: 10.1093/ehjcvp/pvaa014. Full text in Research Archive
• Agewall, Stefan (2020). Focus on pharma in acute coronary syndrome. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(1), p. 1–2. doi: 10.1093/ehjcvp/pvz074. Full text in Research Archive
• Agewall, Stefan (2020). Can we offer tailor-made pharmacological treatment of patients with acute coronary syndrome? European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(4), p. 201–202. doi: 10.1093/ehjcvp/pvaa075. Full text in Research Archive
• Agewall, Stefan (2020). Minimizing bleeding events. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 6(5), p. 271–272. doi: 10.1093/ehjcvp/pvaa100. Full text in Research Archive
• Agewall, Stefan (2019). European Heart Journal - Cardiovascular Pharmacotherapy has received its first Impact Factor of 6.723. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(4), p. 183–184. doi: 10.1093/ehjcvp/pvz041. Full text in Research Archive
• Agewall, Stefan (2019). Antiplatelet treatment in acute coronary syndrome. Still an issue. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(3), p. 125–126. doi: 10.1093/ehjcvp/pvz018. Full text in Research Archive
• Agewall, Stefan (2019). Old and new drugs in cardiovascular pharmacotherapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(1), p. 1–2. doi: 10.1093/ehjcvp/pvy046. Full text in Research Archive
• Marciniak, Thomas A.; Hall, Trygve Sørdahl; Atar, Dan; Agewall, Stefan & Serebruany, Victor L. (2019). Ivabradine for heart failure: Regulatory differences in Europe and United States. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(2), p. 119–121. doi: 10.1093/ehjcvp/pvz006. Full text in Research Archive
• Agewall, Stefan (2019). European Heart Journal - Cardiovascular Pharmacotherapy: Now accepted for an official Impact Factor. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(2), p. 59–59. doi: 10.1093/ehjcvp/pvz009. Full text in Research Archive

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