- Design
- Hospital cohort with genotyping and plasma levels, adjusted Cox models
- Population
- 996 patients taking metoprolol tartrate, Montreal
- Primary outcome
- All-cause mortality, median 101 months
- Effect
- Higher CYP2D6 metaboliser status HR 0.82 (0.67–0.99)
A cohort study in Clinical and Translational Science (1 September) genotyped CYP2D6 in 996 patients taking metoprolol tartrate at the Montreal Heart Institute and measured a random plasma metoprolol level. Over a median of about eight and a half years, 24.3% died.
Higher CYP2D6 metaboliser activity was associated with lower mortality (HR 0.82, 95% CI 0.67–0.99), after adjusting for age, sex, cardiovascular history, other drugs and CYP2D6 inhibitors. Metoprolol concentration itself was not associated with mortality once confounders were accounted for.
CYP2D6 poor metabolisers have several-fold higher metoprolol levels and more bradycardia. Whether that translates into harm has been uncertain. This single-centre association, with an upper confidence limit close to 1, is not enough to change prescribing, but it keeps the question open.
- Watch for excess bradycardia or fatigue on standard metoprolol doses
- Remember common CYP2D6 inhibitors: fluoxetine, paroxetine, bupropion, quinidine
- Consider bisoprolol, which does not depend on CYP2D6, when metoprolol is poorly tolerated
- Do not order routine CYP2D6 testing for metoprolol on this evidence
Why it matters
It suggests a known pharmacokinetic difference might have consequences beyond heart rate.
Don't overread it
This is a single-centre observational association and does not justify genotyping before prescribing.
The statistics, in plain English
A hazard ratio of 0.82 with an upper limit of 0.99 is only just statistically significant. It comes from one cohort, so it needs replication before it is believed.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for clinical pharmacology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free