Table 1.
Efficacy and safety of vorapaxar in key randomized trials
| References | Patients (n) | Population | Drug design | Mean age (years) | Follow-up | Study conclusion |
|---|---|---|---|---|---|---|
| Kosoglou et al34 Phase I | 98 | Healthy Caucasian subjects | Vorapaxar oral single or multiple ascending doses or loading and maintenance doses versus placebo | 25 | 8 weeks | Vorapaxar provided rapid, potent, dose- dependent, durable inhibition of TRAP-induced platelet aggregation. Adverse events were mild and unrelated to dose |
| Kosoglou et al35 Phase I | 111 | Healthy Japanese and matched Caucasian subjects | Vorapaxar oral single or multiple doses | 26 | 8 weeks | Vorapaxar 40 mg completely and rapidly inhibited TRAP-induced platelet aggregation and this effect was maintained with a 2.5 mg daily dose. The drug was well tolerated in both Japanese and Caucasian subjects, with no racial differences |
| TRA-PCI31 Phase II | 1,030 | Elective PCI | Vorapaxar multiple oral loading and maintenance doses versus placebo | 63 | 60 days | Vorapaxar was well tolerated and was not associated with an increase in risk of bleeding compared with placebo in patients undergoing PCI |
| Goto et al36 Phase II | 117 | Japanese subjects with NSTEMI | Vorapaxar two different oral loading and maintenance doses versus placebo | 64 | 60 days | Vorapaxar reduced the incidence of peri- procedural MI in Japanese patients undergoing urgent PCI without resulting in excess bleeding |
| TRACER21 Phase III | 12,944 | NSTEMI | Vorapaxar oral loading dose of 40 mg and a daily maintenance dose of 2.5 mg thereafter versus placebo | 64* | 502 days | Vorapaxar partially reduced ischemic events, but significantly increased bleeding, including major and intracranial bleeding. In a subgroup analysis, vorapaxar significantly reduced the hazard of future MI events |
| TRA 2°P-TIMI 5022 Phase III | 26,449 | Subjects with a history of MI, ischemic stroke, or peripheral arterial disease | Vorapaxar oral dose of 2.5 mg versus placebo | 61* | 30 months | Vorapaxar reduced the risk of composite cardiovascular death, MI, and stroke, with the most benefit observed in patients with a previous history of MI. This however resulted in a significant increase in intracranial hemorrhage in patients with a history of stroke |
Note:
*
median age.
Abbreviations: MI, myocardial infarction; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; TRAP, thrombin receptor activating peptide.