Higher CYP2D6 metabolizer status was associated with lower risk of death (HR=0.82, 95% CI: 0.67-0.99; p=0.04) in metoprolol users, suggesting that CYP2D6-inferred metabolizer status can inform on mortality risk in patients treated with metoprolol.
Higher CYP2D6 metabolizer status was associated with a statistically significant lower risk of death in metoprolol users.
Metoprolol plasma concentrations were not independently associated with mortality after adjustment for confounders.
Overall mortality in the cohort was 24.3% over a median follow-up of approximately 101 months.
CYP2D6 metabolizer status was determined using standardized classifications in a cohort of 996 metoprolol tartrate users.
The authors conclude that larger studies are needed to confirm the association of CYP2D6 metabolizer status with clinical outcomes beyond pharmacokinetic and hemodynamic considerations.
This research suggests that a person's genetic ability to break down the heart medication metoprolol is linked to their risk of dying. Metoprolol is a commonly prescribed beta-blocker used to treat conditions like high blood pressure and heart failure. The gene CYP2D6 controls an enzyme in the liver that processes metoprolol, and people can be classified as poor, intermediate, normal, or ultra-rapid metabolizers depending on how active their version of this gene is. In a study of 996 patients followed for over eight years, those with higher CYP2D6 metabolizer status—meaning they broke down the drug more efficiently—had an 18% lower risk of dying compared to those with lower metabolizer status. Interestingly, simply measuring the amount of metoprolol in a patient's blood was not independently associated with survival once other factors were taken into account, but the genetic classification still was. This suggests that the genetic information captures something about how a patient responds to the drug that goes beyond just drug levels in the blood. The study adjusted for many potential confounding factors including age, sex, cardiovascular history, other medications, and drugs that can block CYP2D6 activity. This research matters because it suggests that genetic testing for CYP2D6 status could potentially help identify which metoprolol patients are at higher mortality risk. However, the authors caution that larger studies are needed to confirm these findings before they could be widely applied in clinical practice. The work adds to a growing body of evidence that pharmacogenomics—studying how genes affect drug response—may have real-world implications for patient survival, not just for drug levels and immediate physiological effects.
de Denus S, Oussaïd E, Meloche M, Bertrand A, Leclair G, Cyr M, et al.. (2026). CYP2D6 Metabolizer Status and Mortality in Metoprolol Users.. Clinical and translational science. https://doi.org/10.1111/cts.70714