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Efficacy and safety of vorapaxar as approved for clinical use in the United States.

ABSTRACT: Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).We examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the multinational, double-blinded, placebo-controlled TRA 2°P-TIMI 50 trial. Of these, 16,897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70.In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long-term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.URL: clinicaltrials.gov Unique Identifier: NCT00526474.

SUBMITTER: Magnani G

PROVIDER: S-EPMC4392433 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Efficacy and safety of vorapaxar as approved for clinical use in the United States.

Magnani Giulia G Bonaca Marc P MP Braunwald Eugene E Dalby Anthony J AJ Fox Keith A A KA Murphy Sabina A SA Nicolau José Carlos JC Oude Ophuis Ton T Scirica Benjamin M BM Spinar Jindrich J Theroux Pierre P Morrow David A DA

Journal of the American Heart Association 20150319 3

<h4>Background</h4>Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).<h4>Methods and results</h4>We examined the efficacy and safety of vorapaxar in the intended use population, considering 20,170 patients randomized in the ...[more]

PMID: 25792124

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Project description:BackgroundNVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.MethodsWe conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.ResultsOf the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose.ConclusionsNVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Project description:BackgroundPerioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS.Methods and resultsIn the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment.ConclusionNCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.

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Efficacy and safety of vorapaxar as approved for clinical use in the United States.

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Efficacy and safety of vorapaxar as approved for clinical use in the United States.

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