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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Consultant Cardiologist Alexander R. Lyon, Royal Brompton Hospital, UK
- Second opponent: Professor Charlotte Manisty, University College London, UK
- Third member and chair of the evaluation committee: Professor Anders Erik Astrup Dahm, University of Oslo
Chair of the Defence
Associate professor Stig Müller, University of Oslo
Principal Supervisor
Professor Torbjørn Omland, University of Oslo
Summary
Cancer therapy-related cardiac dysfunction (CTRCD) is a concern for patients receiving various types of chemotherapeutic agents. Anthracyclines are the cornerstone of adjuvant breast cancer therapy, but their use have been limited by their cardiotoxic effects. Consequently, several strategies to prevent anthracycline-induced cardiotoxicity have been explored, including the use of renin-angtiotensinsystem inhibitors and beta blockers.
The aims of this thesis were to assess the long-term effects of candesartan and metoprolol on cardiac function in women receiving adjuvant anthracycline therapy, to evaluate how the 2022 ESC cardio-oncology guideline biomarker criteria affect the reported incidence of cancer therapy-related cardiac dysfunction (CTRCD), and to present the rationale and design of the PRADA II trial.
The thesis is based on the extended follow-up of the PRADA trial, a randomised, double-blind, placebo-controlled 2x2 factorial trial including 120 women with early breast cancer. Cardiac function was assessed by cardiovascular magnetic resonance imaging, echocardiography, and by measuring cardiovascular biomarkers.
Neither candesartan nor metoprolol prevented the decline in left ventricular ejection fraction at extended follow-up. Candesartan showed modest effects on end-diastolic volume and global longitudinal strain, though clinical relevance remains uncertain. The cumulative incidence of mild asymptomatic CTRCD varied markedly depending on the troponin assay and reference limits applied, ranging from 9.3% to 49.2%. Troponin elevation during treatment did not predict subsequent cardiac dysfunction.
These findings do not support the routine use of candesartan or metoprolol in unselected patients receiving adjuvant breast cancer therapy. Standardisation of biomarker-based diagnostic criteria is needed, and future cardioprotective strategies should be tailored to the individual patient.
avsnitt
Additional information
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