Objective: Methadone is associated with prolongation of the electrocardiographic QTc interval. QTc prolongation may be linked to cardiac dysrhythmia and sudden cardiac death. The rate of these events is unknown in methadone-maintained patients. Methods: This retrospective cohort study of 749 patients with opioid use disorder receiving methadone maintenance therapy through a single safety-net hospital, queried the electronic health record for electrocardiogram results, demographics, methadone dose, and diagnostic codes consistent with cardiac conduction disorder (International Classification of Disease, Ninth Revision [ICD-9] 426) and cardiac dysrhythmia (ICD-9 427). Factors associated with QTc interval were explored; Cox proportional-hazards regression models were used to analyze time to an event that may predispose to sudden cardiac death. Results: One hundred thirty-four patients had an electrocardiogram while on methadone, 404 while off methadone, and 211 both while on and off methadone. Mean QTc interval while on methadone (436ms, SD 36) was significantly greater than while off methadone (423ms, SD 33). Age and methadone dose were weakly associated with increased QTc interval (P<0.01 and P<0.0005, respectively, adjusted R 2 =0.05). There were 44 ICD-9 426 and 427 events over 7064 patient-years (6.3events/1000 patient-yrs). Having a QTc greater than sex-specific cut-off values was significantly associated with time to event (hazard ratio 3.32, 95% confidence interval 1.25-8.81), but being on methadone was not. Conclusions: Methadone is associated with QTc prolongation in a nonclinically significant dose-related manner. Cardiac events were rare and the sudden cardiac death rate was below that of the general population. Current recommendations for cardiac risk assessment in methadone-maintained patients should be reconsidered.
Bibliographical noteFunding Information:
From the Department of Medicine, Hennepin County Medical Center, Min-neapolis, MN (GB, RK, BAB); Pharmacy Department, Hennepin County Medical Center, Minneapolis, MN (ZW); Biostatistical Design and Anal-ysis Center, University of Minnesota, Minneapolis, MN (QW, JSH); and Division of Biostatistics, School of Public Health, University of Minne-sota, Minneapolis, MN (JSH). Received for publication June 9, 2017; accepted August 4, 2017. Funding: This work was supported by a National Institutes of Health– National Institute on Drug Abuse career development award K23 DA024663 (G.B.). The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.journaladdictionmedicine.com). Send correspondence to Gavin Bart, MD, PhD, Department of Medicine, G-5, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415. E-mail: firstname.lastname@example.org Copyright © 2017 American Society of Addiction Medicine ISSN: 1932-0620/17/1106-0489 DOI: 10.1097/ADM.0000000000000353
© 2017 American Society of Addiction Medicine.
- QTc interval
- event rate
- sudden cardiac death