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. 2013 Oct 1;112(7):1013-8.
doi: 10.1016/j.amjcard.2013.05.037. Epub 2013 Jun 29.

QTc interval screening in an opioid treatment program

David F Katz  1 , Jun Sun, Vaishali Khatri, David Kao, Becki Bucher-Bartelson, Carol Traut, John Lundin-Martinez, Michael Goodman, Philip S Mehler, Mori J Krantz
Affiliations

QTc interval screening in an opioid treatment program

David F Katz et al. Am J Cardiol. .

Abstract

Methadone is highly effective for opioid dependency, but it is associated with Torsade de pointes. Although electrocardiography (ECG) has been proposed, its utility is uncertain, because an ECG-based intervention has not been described. An ECG-based cardiac safety program in methadone maintenance patients was evaluated in a single opioid treatment program from September 1, 2009, to August 31, 2011, in the United States. Time from pretreatment to repeat ECG in new entrants was assessed. The proportion with marked rate-corrected QT (QTc) interval prolongation (>500 ms) and the effect of the intervention on the QTc interval in this group were evaluated. Multivariate predictors of QTc interval change were assessed using a mixed-effects model. Of 531 new entrants, 436 (82%) underwent ≥1 electrocardiographic assessment, and 186 (35%) underwent pretreatment ECG. Median time to follow-up ECG was 43 days but decreased over time (p <0.0001). In 21 patients with QTc intervals >500 ms, the mean QTc interval from peak to final ECG decreased significantly (-55.5 ms, 95% confidence interval -77.0 to -33.9, p = 0.001), and 12 of 21 (57.1%) decreased to lower than the 500-ms threshold. In new entrants with serial ECG, only methadone dose (p = 0.009) and pretreatment QTc interval (p <0.0001) were associated with the magnitude of QTc interval change. In conclusion, this study suggests that the implementation of an ECG-based intervention in methadone maintenance can decrease the QTc interval in high-risk patients; clinical characteristics alone were inadequate to identify patients in need of electrocardiographic screening.

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Conflict of interest statement

Declaration of Interests

Data management and statistical analysis was supported by the Colorado Clinical Translation Science Institutes. Qualitative evaluation and analysis was supported by the Glassman Endowment. Dr. Krantz was partially supported by AHRQ Grant 1 P01 HS021138-01. Dr. Krantz was a member of the FDA Cardiovascular and Renal Drugs Advisory Committee and attended the joint meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on July 22 and 23, 2010 that including discussion of methadone and arrhythmia risk. He has served as a consultant for design of a thorough QTc interval study for Reckitt Benckiser Pharmaceuticals Inc. (no personal remuneration) and CoLucid Inc (minimal). The RADARS® System is a division of Denver Health and Hospital Authority, a state governmental organization. The RADARS® System provides post-marketing surveillance of prescription medications to pharmaceutical manufacturers. Several manufacturers of controlled substances are subscribers to the RADARS® System. Jun Sun, Vaishali Khatri and Becki Bucker-Bartelson are employees of Denver Health and Hospital Authority, which operates the RADARS® System. They have no direct financial or non-financial relationships with pharmaceutical companies outside of their roles at Denver Health and Hospital Authority. No other authors report relevant disclosures of financial or other interest.

Figures

Figure 1
Figure 1
QTc Interval Changes from Baseline to Follow-up.
Figure 2
Figure 2
Time to Follow-Up ECG in Patients with a Pretreatment ECG. The dot represents the mean number of days to ECG; the middle bar represents the median. The minimum, maximum, 25th and 75th percentiles are depicted with the boxplots. Period 1 is 9/1/09–2/28/10, Period 2 is 3/1/10–8/31/10, Period 3 is 9/1/10–2/28/11, and period 4 is 3/1/11–8/31/11. No newly enrolled patients had a pretreatment ECG during Period 1 of the study. Median days to follow-up ECG during periods 2–4 were 101, 47, and 29 days respectively (p< 0.0001 using ranked data and linear regression).
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