Thrombin-Receptror Antagonist Vorapaxar in Acute Coronary Syndromes
Topic: Anticoagulation in acute coronary syndrome (direct thrombin inhibitors)
- Determine benefit vorapaxar (a protease-activated-receptor 1 antagonists that inhibits thrombin-induced platelet activation) in patients with non-STEMI ACS.
- International, randomized, double-blinded, clinical trial.
- Vorapaxar (40 mg loading dose and daily maintenance dose of 2.5 mg). Other standard therapies were given at the discretion of the treating physician.
- Placebo. Other standard therapies were given at the discretion of the treating physician.
- 12,944 patients
- Ischemic symptoms 24 hours before hospital presentation and at least one of the following: elevated cardiac biomarkers, ST segment elevation or depression. Also required one of the following: 55 years or older, prior MI, DM, or PAD.
- Complete list in supplemental materials.
- 502 days
- Composite of death from cardiovascular causes, MI, stroke, recurrent ischemia with hospitalization, or urgent coronary revascularization.
- Composite of cardiac death, MI, or stroke.
- Mean age 64 years, 28% female.
- 91.8% of patients received clopidogrel, 88.1% received angiography, 57.8%received PCI, and CABG was done in 10.1% of patients.
- Composite of the primary outcome occurred in 1031 of 6473 patients in the vorapaxar group vs 1102 of 6471 in the placebo group (18.5% vs 19.9%; HR 0.92, CI 0.85-1.01; P=0.07).
- Secondary endpoint occurred in 14.7% of patients in the vorapaxar group compared to 16.4% of patients in the placebo group (HR 0.89; CI 0.81-0.98; P=0.02).
- Reduction in the rate of MI was the main effect in the secondary endpoints.
- Rate of clinically significant TIMI bleeding was increased among patients with vorapaxar (20.2% vs 14.6%; HR 1.43, CI 1.31-1.57; P<0.0001), including rates of intracranial hemorrhage.
- Patients with low body weight were at higher risk of bleeding.
TAKE AWAY: Vorapaxar when added to standard therapy did not significantly reduce primary composite endpoints and was associated with significantly increased risk of major bleeding, including intracranial hemorrhage.