Abstract
Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug-gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug-gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683-0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722-0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030-1.329, p = 0.016). The Kaplan-Meier survival curves showed that compared to patients without a drug-gene pair, a significantly lower risk of MACEs could be observed in patients with a drug-gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325-0.951, p = 0.013). In conclusion, the carrier status of the actionable drug-gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients.