The novel direct thrombin inhibitor bivalirudin is now widely used as an adjunctive therapy in patients undergoing primary PCI for ST elevation myocardial infarction (STEMI). This stems from trial data demonstrating bivalirudin results in lower bleeding rates and better long term survival as compared with the combination of heparin and a GP IIb/IIIa inhibitor. However, clinical practice has subsequently changed, including greater use of radial access with resultant lower bleeding risk and expanded use of newer generation P2Y12 inhibitors. The EUROMAX trial sought to understand whether use of bivalirudin benefits patients in light of these changes in clinical practices.
This trial prospectively randomized 2218 patients in an open-label fashion to treatment with bivalirudin or heparin with optional use GP IIb/IIIa (decision left to provider preference) inhibitor by paramedic teams during ambulance transfer to a PCI center. Approximately 50% of procedures were completed radially with 60% of patients being loaded with one of the novel P2Y12 antagonists. Nearly 70% of patients in the heparin group received a GP IIb/IIIa inhibitor compared to just over 10% in the bivalirudin treated group. The primary endpoint was the composite of death and major bleeding at 30-days. Bivalirudin resulted a lower event rate (5.1% vs. 8.5%; relative risk [RR], 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) due to lower bleeding events, but not mortality benefit (2.9% vs. 3.1%). Furthermore, bivalirudin therapy resulted in a significant increase in the rate of acute stent thrombosis (1.1% vs. 0.2%; RR, 6.11; 95% CI, 1.37 to 27.24; P=0.007).
In this large contemporary practice trial with frequent use of radial access and novel P2Y12 inhibitors, early use of bivalirudin use in STEMI patients led to reduced bleeding events, but increased rates of acute stent thrombosis. This investigation is timely, given the impact of radial access on baseline bleeding risk and newer P2Y12 inhibitors on thrombotic risk. However, as procedural technique and antiplatelet therapies continuing to evolve, the relative benefit of bivalirudin may continue to warrant investigation with changes in practice.
- Steg PG, van ‘t Hof A, Hamm CW, Clemmensen P, Lapostolle F, Coste P, Berg JT, Van Grunsven P, Eggink GJ, Nibbe L, Zeymer U, Orto MC, Nef H, Steinmetz J, Soulat L, Huber K, Deliargyris EN, Bernstein D, Schuette D, Prats J, Clayton T, Pocock S, Hamon M and Goldstein P. Bivalirudin Started during Emergency Transport for Primary PCI. N Engl J Med. 2013 Oct 30. [Epub ahead of print]