DENVER — Methadone in therapeutic doses appears to be associated with increased risk of sudden cardiac death, Dr. Carmen Socoteanu reported at the annual meeting of the Heart Rhythm Society.
This observation from a prospective case-control study has important public health implications in light of how widely the drug is prescribed for chronic pain control and opioid addiction, added Dr. Socoteanu of Oregon Health and Science University, Portland.
She reported on 22 consecutive cases of sudden cardiac death (SCD) featuring therapeutic blood levels of methadone. The cases were evaluated by the state medical examiner with detailed autopsies as part of the ongoing Oregon Sudden Unexplained Death Study sponsored by the Centers for Disease Control and Prevention.
Controls comprised 106 consecutive cases of SCD with no evidence of methadone on toxicology screening during the same 4-year period. Individuals with evidence of recreational drug use or any drug overdose, including a blood methadone level of more than 1 mg/L, were excluded.
The mean age of individuals with therapeutic blood levels of methadone deemed to have experienced SCD was 37 years, compared with 42 years for controls.
Among controls, a specific cardiac cause of SCD was identified in 60% of cases. In contrast, a cardiac cause could be identified in only 5 of 22 methadone users, or 23%, leaving therapeutic use of methadone as the only identifiable potential etiology of SCD in the great majority of cases.
Dr. John P. DiMarco commented that he would take home a key lesson from the study: a reminder that noncardiac drugs can cause arrhythmias and cardiac death.
When physicians think about proarrhythmic drugs, they tend to focus on antiarrhythmic agents and other cardiac medications. That's particularly true of cardiologists. But methadone is an IKr potassium channel blocker that prolongs the QT interval and can cause torsades de pointes, noted Dr. DiMarco, professor of medicine and director of the electrophysiology service at the University of Virginia, Charlottesville.
Late last year, the Food and Drug Administration issued a public health advisory and ordered methadone labeling changes because of the mounting evidence of serious adverse events.