Evidence-Based Answers

Evidence Central™ is an integrated web and mobile solution that helps clinicians quickly answer etiology, diagnosis, treatment, and prognosis questions using the latest evidence-based research.


Evidence Central for Mobile Devices

Evidence Central iOS iPhone iPad Android

Evidence Central from Unbound Medicine, available for iOS® and Android™, is optimized for each platform and features superior navigation, so answers are easy to find at the bedside or anywhere they’re needed. Learn More

Word of the Day

Vorapaxar has benefits but increases risk of serious bleeding

Clinical Question:
Does adding vorapaxar to aspirin improve outcomes in patients with a cardiovascular disease?

Bottom Line:
Vorapaxar reduces the likelihood of a combined outcome of cardiovascular death, myocardial infarction (MI), and stroke (number needed to treat [NNT] = 83), but does not reduce all-cause mortality and increases the risk of serious bleeding complications such as intracerebral hemorrhage (number needed to treat to harm [NNTH] = 200). This drug is not yet approved by the Federal Drug Administration. (LOE = 1b)

Morrow DA, Braunwald E, Bonaca MP, et al, for the TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012;366:1404-13.  [PMID:22443427]

Study Design:
Randomized controlled trial (double-blinded)



Outpatient (any)

Vorapaxar inhibits thrombin activation of platelets via competitively blocking the PAR-1 receptor on platelets. As this mechanism is different from that of aspirin, these researchers theorized that adding vorapaxar to aspirin would improve clinical outcomes. In this large multisite study, 26,449 patients with a history of stroke, MI, or peripheral vascular disease were randomized to receive vorapaxar 2.5 mg once daily or placebo. Patients also continued taking other antiplatelet medications that have different mechanisms of action. Aspirin was used by 94% of the patients; 78% had a history of MI; and a substantial number were also taking clopidogrel, ticlodipine, or dipyridamole. The groups were well balanced at the start of the study, with a median age of 61 years. Approximately 25% were women. Patients were followed up for up to 49 months (median = 30 months). The primary outcome was assessed after 3 years of follow-up and revealed a mixed bag of benefits and harms. The primary efficacy outcome was the combination of cardiovascular death, MI, and stroke, and was reduced in the vorapaxar group (9.3% vs 10.5%; P < .001; NNT = 83). However, there was no difference in the likelihood of all-cause mortality (5.0% vs 5.3%), cardiovascular death, or any stroke between groups. And, there was a significant increase in the likelihood of moderate or severe bleeding (4.2% vs 2.5%; P < .001; NNTH = 59) and an increased risk of intracerebral hemorrhage (1.0% vs 0.5%; P < .001; NNTH = 200) that was greater in patients with a previous history of stroke (2.4% vs 0.9%; P < .001; NNTH = 67).


Site Licenses

Site license

Site Licenses are available for schools, universities, hospitals, government agencies, and companies. For more information, contact us.