A Pharmacogenetic Panel-Based Prediction of the Clinical Outcomes in Elderly Patients with Coronary Artery Disease
Lisha Dong1,2, Shizhao Zhang1,2, Chao Lv1
1Institute of Geriatrics, National Clinical Research Center for Geriatric Diseases, Second Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
Insights
Pharmacogenetic testing in elderly coronary artery disease (CAD) patients on polypharmacy revealed that 80.3% had actionable drug-gene pairs. Carrier status predicts clinical outcomes, suggesting pharmacogenetic panel-guided therapy can improve patient results.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Geriatrics
Background:
- Actionable pharmacogenetic variants influencing cardiovascular drug efficacy are known, but their impact on elderly patients with coronary artery disease (CAD) on polypharmacy is unclear.
- Polypharmacy in elderly CAD patients increases risks of adverse drug reactions and suboptimal therapeutic outcomes.
- Understanding drug-gene interactions is crucial for optimizing treatment in this vulnerable population.
Purpose of the Study:
- To investigate the impact of actionable pharmacogenetic variants on clinical outcomes in elderly CAD patients undergoing polypharmacy.
- To determine the association between drug-gene pairs and major adverse cardiovascular events (MACEs), all-cause mortality, and adverse drug reactions (ADRs).
- To evaluate the potential of pharmacogenetic panel-guided polypharmacy for improving patient outcomes.
Main Methods:
- A cohort of 892 elderly patients (mean age 80.7 years) with CAD and polypharmacy was enrolled.
- Genotyping was performed for 13 variants in 10 pharmacogenes relevant to 12 commonly prescribed CAD drugs.
- Statistical analyses, including adjusted hazard ratios and Kaplan-Meier survival curves, were used to assess outcomes over a 4-year follow-up period.
Main Results:
- 80.3% of patients had at least one actionable drug-gene pair requiring a therapeutic drug change.
- The number of drug-gene pairs was independently associated with a decreased risk of MACEs (aHR: 0.803) and all-cause mortality (aHR: 0.848).
- An increased risk of ADRs (aHR: 1.170) was observed with more drug-gene pairs, while patients with any drug-gene pair showed a significantly lower risk of MACEs compared to those without (HR: 0.556).
Conclusions:
- Carrier status of actionable drug-gene pairs is predictive of clinical outcomes in elderly CAD patients on polypharmacy.
- Implementing preemptive pharmacogenetic panel-guided polypharmacy may enhance clinical outcomes for this patient group.
- Pharmacogenetic insights are essential for personalized cardiovascular pharmacotherapy in the elderly.
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.
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