Vorapaxar

Vorapaxar Brand Name

Zontivity

What is Vorapaxar

Vorapaxar is a competitive and selective antagonist of protease-activated receptor-1 (PAR-1), the major thrombin receptor on human platelets.

It is approved for reduction in risk of myocardial infarction, stroke, cardiovascular death, and need for coronary revascularization in patients with a previous myocardial infarction or peripheral arterial disease (PAD).

Vorapaxar potently inhibits thrombin-related platelet aggregation thereby decreasing the formation of blood clots.

Like other agents that interfere with clotting, vorapaxar increases the risk of bleeding, including life-threatening or fatal bleeding. Vorapaxar was granted FDA approval based on results of the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2P)–Thrombolysis in Myocardial Infarction (TIMI) 50 trial.

More than 25,000 patients with a history of myocardial infarction (MI), ischemic stroke, or PAD were randomized to vorapaxar or placebo in addition to standard therapy (i.e., aspirin and/or thineopyridines) with a median follow-up of 30 months. After 2 years, the data and safety monitoring board recommended discontinuation of vorapaxar in patients with a history of stroke including those with a new stroke during the trial due to an increased risk of intracranial hemorrhage in this population.

In post-MI or PAD patients without a history of stroke or transient ischemic attack, the 3-year Kaplan-Meier (K-M) event rate for the primary efficacy endpoint (composite of time to first cardiovascular death, MI, stroke, or urgent coronary revascularization) was 10.1% in the vorapaxar group compared to 11.8% in the placebo group (HR 0.83, 95% CI 0.76 to 0.9; p < 0.001).

The K-M event rate for the key secondary efficacy endpoint (composite of time to first CV death, MI, or stroke) was 7.9% in the vorapaxar group compared to 9.5% in the placebo group (HR 0.80, 95% CI 0.73 to 0.89; p < 0.001).

Vorapaxar was FDA-approved in May 2014.

Indications & Dosage

  • myocardial infarction prophylaxis
  • stroke prophylaxis
  • thrombosis prophylaxis

For secondary myocardial infarction prophylaxis or stroke prophylaxis or thrombosis prophylaxis for reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease

Side Effects

  1. anemia
  2. bleeding
  3. depression
  4. diplopia
  5. GI bleeding
  6. intracranial bleeding
  7. rash
  8. retinopathy

Monitoring Parameters

  • laboratory monitoring not necessary

Contraindications

  • bleeding
  • breast-feeding
  • coronary artery bypass graft surgery (CABG)
  • geriatric
  • hepatic disease
  • intracranial bleeding
  • pregnancy
  • renal impairment
  • stroke
  • surgery

Interactions

  • Abciximab
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
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  • Amoxicillin; Clarithromycin; Omeprazole
  • Anagrelide
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  • Antithymocyte Globulin
  • Apalutamide
  • Apixaban
  • Aprepitant, Fosaprepitant
  • Ardeparin
  • Argatroban
  • Armodafinil
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
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