Vorapaxar in the Secondary Prevention of Atherothrombotic Events
Topic: Anticoagulation in acute coronary syndrome (direct thrombin inhibitors)
- Determine efficacy of vorapaxar in secondary prevention in patients with known atherosclerosis.
- Multinational, double-blind, placebo-controlled trial
- Vorapaxar (2.5 mg daily)
- 26,449 patients
- History of atherosclerosis(defined by history of MI, stroke, PAD, or claudication).
- Planned revascularization
- History of bleeding
- On anticoagulation
- Active hepatobiliary disease
- 30 months
- Composite of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to urgent coronary revascularization
- GUSTO moderate or severe bleeding.
- Composite of cardiovascular death, myocardial infarction, or stroke.
- Mean age 61, 24% were women.
- Comorbidities equal between groups; 67% had history of MI, 18% history of stroke.
- 98.1% of patients in both groups were taking aspirin, 70% were taking a thienopyridine antiplatelet agent.
- Primary end point of cardiovascular death, myocardial infarction, or stroke had occurred in 1028 patients (9.3%) in the vorapaxar group, as compared with 1176 patients (10.5%) in the placebo group (HR 0.87; CI 0.80 to 0.94; P<0.001; benefit strongest in patients with history of MI).
- Major secondary end point of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization occurred in 1259 patients (11.2%) in the vorapaxar group, as compared with 1417 patients (12.4%) in the placebo group (HR 0.88; CI, 0.82 to 0.95; P=0.001).
- Among patients with no history of stroke, the primary end point occurred in 8.3% of patients in the vorapaxar group, as compared with 9.6% of those in the placebo group (HR 0.84; CI, 0.76 to 0.93; P<0.001).
- In patients with history of stroke, vorapazar was discontinued early on the basis of an excess of CNS bleeding in such patients.
- The major safety end point of moderate or severe bleeding (according to GUSTO criteria) occurred in 438 patients (4.2%) in the vorapaxar group, as compared with 267 patients (2.5%) in the placebo group (HR 1.66; 95% CI, 1.43 to 1.93; P < 0.001).
- Intracranial hemorrhage occurred in 102 patients (1.0%) in the vorapaxar group, as compared with 53 patients (0.5%) in the placebo group (HR 1.94; CI, 1.39 to 2.70; P<0.001).
TAKE AWAY: Reduction of thrombotic events (CV death, MI, or stroke) with vorapaxar in patients with stable artherossclerosis comes with a significant increased risk of major bleeding, especially in patients with history of stroke.