Prevalence and clinical relevance of QTc prolongation during methadone and buprenorphine treatment: A mortality assessment study
This study investigates the prevalence of QTc prolongation among opioid maintenance treatment (OMT) patients in Oslo in relation to: type of agonist (methadone or buprenorphine), dose, gender and length of treatment.
We also estimate the extent to which deaths occurring in the Norwegian OMT programme might be attributed to QTc prolongation. The knowledge of such deaths within the first month in treatment is of particular importance, as it is the time when the OMT medication is first being introduced. Additionally, undetected deaths early in treatment due to TdP, might reduce the detected prevalence of QTc prolongation, and hence, its ascribed significance.
To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT); and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme.
Participants and Setting
200 OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997-December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT.
Design and Measures
The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient years in OMT.
In the QTc assessment sample (n=200), 173 patients (86.5 %) received methadone and 27 (13.5 %) received buprenorphine. In the methadone group, 4.6 % (n=8) had a QTc above 500 msec: 15 % (n=16) had a QTc interval above 470 msec: 28.9 % (n=50) had a QTc above 450 msec. All patients receiving buprenorphine (n=27) had QTc results < 450 msec. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 msec were taking methadone doses of 120 mg or more. The mortality of OMT patients, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient years. Only one death among 3850 OMT initiations occurred within the first month of treatment.
Of the methadone patients, 4.6 % had QTc intervals above 500 msec. The maximum mortality attributable to QTc prolongation was low; 0.06 per 100 patient years.
Addiction 2009; 104: 993-999.