One-Year Mortality for Bivalirudin vs Heparins Plus Optional Glycoprotein IIb/IIIa Inhibitor Treatment Started in the Ambulance for ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the EUROMAX Randomized Clinical Trial

JAMA Cardiol. 2017 Jul 1;2(7):791-796. doi: 10.1001/jamacardio.2016.5975.

Abstract

Importance: Uncertainty exists regarding potential survival benefits of bivalirudin compared with heparin with routine or optional use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction (STEMI). Few data are available regarding long-term mortality in the context of contemporary practice with frequent use of radial access and novel platelet adenosine diphosphate P2Y12 receptor inhibitors.

Objective: To assess the effect of bivalirudin monotherapy compared with unfractionated or low-molecular-weight heparin plus optional GPIs on 1-year mortality.

Design, setting, and participants: This international, randomized, open-label clinical trial (EUROMAX [European Ambulance Acute Coronary Syndrome Angiography]) included 2198 patients with STEMI undergoing transport for primary percutaneous coronary intervention from March 10, 2010, through June 20, 2013, and followed up for 1 year. Patients were randomized (1:1) in ambulance to bivalirudin monotherapy vs unfractionated or low-molecular-weight heparin plus optional GPIs (control group). Analysis was based on intention to treat.

Main outcomes and measures: The primary outcome of this prespecified analysis was 1-year mortality. All deaths were adjudicated as cardiac or noncardiac by an independent, blinded clinical events committee. One-year mortality was assessed and examined across multiple prespecified subgroups.

Results: Of the 2198 patients enrolled (1675 men [76.2%] and 523 women [23.8%]; median [interquartile range] age, 62 [52-72] years), complete 1-year follow-up data were available for 2164 (98.5%). All-cause 1-year mortality occurred in 118 patients (5.4%). The number of all-cause deaths was the same for both treatment groups (59 deaths; relative risk [RR], 1.02; 95% CI, 0.72-1.45; P = .92). No differences were noted in the rates of 1-year cardiac death (44 [4.0%] for the bivalirudin group vs 48 [4.3%] for the control group; RR, 0.93; 95% CI, 0.63-1.39; P = .74) or noncardiac death (15 [1.4%] for the bivalirudin group vs 11 [1.0%] for the control group; RR, 1.39; 95% CI, 0.64-3.01; P = .40). Results were consistent across the prespecified patient subgroups. The rate of deaths occurring from 30 days to 1 year was also similar (27 [2.5%] in the bivalirudin group vs 25 [2.3%] in the control group; RR, 1.10; 95% CI, 0.64-1.88; P = .73).

Conclusions and relevance: In patients with STEMI who were being transported for primary percutaneous coronary intervention, treatment with bivalirudin or with heparin with optional use of GPI resulted in similar 1-year mortality. The reduced composite end point of death and/or major bleeding at 30 days in the bivalirudin arm of the EUROMAX trial did not translate into reduced cardiovascular or all-cause death at 1 year.

Trial registration: clinicaltrials.gov Identifier: NCT01087723.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ambulances
  • Anticoagulants / therapeutic use
  • Antithrombins / therapeutic use*
  • Drug Therapy, Combination
  • Emergency Medical Services
  • Female
  • Heparin / therapeutic use*
  • Hirudins
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Peptide Fragments / therapeutic use*
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Recombinant Proteins / therapeutic use
  • ST Elevation Myocardial Infarction / therapy*

Substances

  • Anticoagulants
  • Antithrombins
  • Hirudins
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • Heparin
  • bivalirudin

Associated data

  • ClinicalTrials.gov/NCT01087723