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Efficacy and safety of vorapaxar for secondary prevention in low body weight in patients with atherosclerosis: analyses from the TRA 2°P-TIMI 50 Trial.
BACKGROUND: Vorapaxar inhibits the thrombin-mediated activation of platelets, reduces thrombotic events in patients with myocardial infarction or peripheral arterial disease while increasing bleeding. In the TRA 2°P-TIMI 50 trial, we observed a nominally significant interaction between low body weight and the reduced efficacy of vorapaxar.
METHODS: We investigated the relationship between body weight and the efficacy and safety of vorapaxar within a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar in patients with atherosclerosis. This analysis was performed among 20,138 patients with a clinical indication for vorapaxar.
RESULTS: Compared with patients weighing 60 kg or more, patients weighing less than 60 kg were older, more frequently women, Asian and had renal insufficiency (each P<0.001). The efficacy of vorapaxar with respect to cardiovascular death, myocardial infarction and stroke showed a significant interaction with patients' weight (Pinteraction<0.03). However among patients younger than 65 years, vorapaxar reduced the primary endpoint regardless of weight (weight ≥60 kg: 6.4% vs. 8.1%, hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.65-0.86; weight <60 kg: 5.4% vs. 7.2%, HR 0.75, 95% CI 0.37-1.49, Pinteraction=0.98). Among patients aged 65 years and older, the efficacy of vorapaxar diminished in patients weighing less than 60 kg (high weight: 10.4% vs. 12.6%, HR 0.81, 95% CI 0.69-0.95; low weight: 16.1% vs. 9.0%, HR 1.62, 95% CI 0.95-2.76, Pinteraction=0.01). The relative increase in bleeding with vorapaxar was not modified by weight (all Pinteraction>0.05).
CONCLUSIONS: Vorapaxar reduced vascular events and improved net clinical outcome regardless of body weight in younger patients. Elderly patients with low weight may not be good candidates for aggressive secondary prevention with vorapaxar added to standard therapy.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov Unique identifier: NCT00526474.
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