- This prematurely terminated trial suggests that using pharmacogenomics to choose antiplatelet agent for patients with acute coronary syndrome (ACS) might improve outcomes.
- Editorial raises concerns about type 1 error.
Why this matters
- Among P2Y12 receptor antagonists (clopidogrel [Plavix], prasugrel [Effient], or ticagrelor [Brilinta]), clopidogrel has comparatively modest effect.
- Patient response to clopidogrel varies based partly on genetics.
- 12-month, randomized, prospective, multicenter clinical trial, PHARMCLO (Pharmacogenetics of Clopidogrel in Patients with Acute Coronary Syndromes).
- 888 patients hospitalized with ACS randomly assigned to be prescribed P2Y12 receptor antagonist based on clinical variables alone vs clinical variables plus genotype.
- Latter group underwent testing for clopidogrel responsiveness via bedside “disposable lab-on-chip” yielding results in 70 minutes.
- Providers also prescribed based on clinical judgment.
- Outcome: composite of cardiovascular death, ischemia, bleeding.
- Funding: Emilia Romagna regional government, Italy.
- Trial halted at 24.6% recruitment because of regulatory issues.
- Across all patients, primary outcome reached in:
- Pharmacogenomic arm: 71 patients (15.9%).
- Standard-of-care arm: 114 (25.9%).
- HR: 0.58 (95% CI, 0.43-0.78; P<.001>
- Standard-of-care arm undertreated and had more events.
- Given early termination, results could be due to chance.
- Genes’ relationship to clopidogrel-related outcomes “ambiguous” per editorial.