Hamostaseologie 2012; 32(03): 221-227
DOI: 10.5482/HAMO-12-05-0006
Review
Schattauer GmbH

Vorapaxar expands antiplatelet options

Which patients may benefit from thrombin receptor antagonism?Vorapaxar erweitert die Möglichkeiten der Plätt-chenhemmungWelche Patienten könnten von Thrombinrezeptor-Antagonisten profitieren?
D. Duerschmied
1   Cardiology and Angiology, University Medical Center Freiburg
,
C. Bode
1   Cardiology and Angiology, University Medical Center Freiburg
› Author Affiliations
Further Information

Publication History

received: 21 May 2012

accepted: 05 July 2012

Publication Date:
28 December 2017 (online)

Summary

Vorapaxar is the first substance of a new class of antiplatelet drugs that has been tested in large clinical trials. The protease-activated receptor 1 (PAR-1) antagonist inhibits thrombin-induced platelet activation to prevent atherothrombosis. In the phase 3 trials TRACER (acute coronary syndrome) and TRA 2P-TIMI 50 (stable atherosclerosis) reducing ischemic events with vorapaxar came at the cost of bleeding.

TRACER compared vorapaxar to placebo in 12 944 patients who had non-ST-segment elevation acute coronary syndromes on top of contemporary treatment including dual antiplatelet therapy (aspirin and clopidogrel). Vorapaxar reduced ischemic events non-significantly, but increased bleeding significantly, therefore not justifying triple antiplatelet therapy in this setting. Follow-up was stopped early because of bleeding. TRA 2P-TIMI 50 examined 26 449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease. Vorapaxar reduced ischemic events and increased bleeding both significantly. Recruitment of patients with prior stroke was stopped early. Net clinical outcome and subgroup analyses suggested that vorapaxar could be beneficial for patients with prior myocardial infarction – but no history of stroke.

Zusammenfassung

Vorapaxar ist der erste Vertreter einer neuen Klasse plättchenhemmender Substanzen, der in großen klinischen Studien getestet wurde. Als oraler Protease-aktivierter Rezeptor-(PAR-)1-Antagonist hemmt es die thrombinin-duzierte Plättchenaktivierung. In den Phase-3-Studien TRACER (akutes Koronarsyndrom) und TRA 2P-TIMI 50 (stabile Atherosklerose) ging die Reduktion ischämischer Ereignisse mit vermehrten Blutungen einher. TRACER verglich Vorapaxar mit Placebo in 12 944 Patienten mit akutem Koronarsyndrom ohne ST-Hebung zusätzlich zur leitlini-engerechten Therapie mit dualer Plättchen-hemmung (Aspirin und Clopidogrel). Vorapa-xar reduzierte den ischämischen Endpunkt nicht-signifikant, steigerte aber die Blutungs-rate so deutlich, dass die dreifache Plättchen-hemmung hier nicht gerechtfertigt erscheint. Das Follow-up wurde wegen der Blutungs-komplikationen frühzeitig gestoppt. TRA 2P-TIMI 50 untersuchte 26 449 stabile Patienten mit vorangegangenem Myokardinfarkt, Schlaganfall oder peripherer arterieller Ver-schlusskrankheit. Die Rekrutierung nach Schlaganfall wurde vorzeitig gestoppt. Vorapaxar reduzierte ischämische Ereignisse und erhöhte Blutungen signifikant. Analysen von Netto-Outcome und Subgruppen zeigten, dass Vorapaxar für Patienten mit voraus-gegangenem Myokardinfarkt – aber ohne Schlaganfall – vorteilhaft sein kann.

 
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