Bivalirudin Started during Emergency Transport for Primary PCI (EUROMAX TRIAL)
Selected in The New England Journal of Medicine by G. Harris
Philippe Gabriel Steg, M.D., Arnoud van 't Hof, M.D., Ph.D., Christian W. Hamm, M.D., Peter Clemmensen, M.D., Ph.D., Frédéric Lapostolle, M.D., Ph.D., Pierre Coste, M.D., Jurrien Ten Berg, M.D., Ph.D., Pierre Van Grunsven, M.D., Gerrit Jan Eggink, M.D., Lutz Nibbe, M.D., Uwe Zeymer, M.D., Marco Campo dell' Orto, M.D., Holger Nef, M.D., Jacob Steinmetz, M.D., Ph.D., Louis Soulat, M.D., Kurt Huber, M.D., Efthymios N. Deliargyris, M.D., Debra Bernstein, Ph.D., Diana Schuette, Ph.D., Jayne Prats, Ph.D., Tim Clayton, M.Sc., Stuart Pocock, Ph.D., Martial Hamon, M.D., and Patrick Goldstein, M.D. for the EUROMAX Investigators
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The HORIZON’s AMI trial demonstrated the superior reduction,at 30 days, in major bleeding and major adverse cardiovascular events,when using the direct thrombin inhibitor bivalirudin (with post stenting “bail out” use of glycoprotein IIb/IIIA inhibitor [used in 7.2% of patients]) vs routine heparin plus Glycoprotein IIb/IIIa inhibitor in patients presenting with STEMI undergoing primary PCI, within 12hrs of symptom onset.
Not only did bivalirudin reduce the rates of major bleeding in this trial, but also the rates of thrombocytopenia and blood transfusion. The dangers of major bleeding have been reported on several occasions (Circulation 2006,American Journal of Cardiology 2003; JAMA 2004, ACUITY trial & REPLACE-2 trial).
Would the early (pre hospital) initiation of bivalirudin, including use of radial PCI and early initiation, of P2Y12 inhibitors concur with the results of HORISONS-AMI and negate the finding of early acute stent thrombosis?
The increased incidence of acute in stent thombosis in the HORISONS-AMI trial, resulted in the EUROMAX trial protocol including the use of aspirin with either ticagrelor or prasugrel with the first medical contact.
The primary outcome in the EUROMAX trial was a composite of death from any cause or non-CABG related major bleeding at 30 days. The main 2e outcome was a composite of all-cause mortality, reinfarction, or non-CABG related major bleeding.
- The bivalirudin arm demonstrated a superior 1e outcome (5.1% vs 8.5%; P=0.001) vs the control intervention arm. I.e., a 3.4% absolute risk reduction (40% relative risk reduction) in major bleeding and death @ 30day.
- The same for the main 2e outcome (6.6% vs. 9.2%; P=0.002),a 28% relative risk reduction.
- There was no difference in the rates of reinfarction (1.7% vs. 0.9%) or death (2.9% vs. 3.1%).
- The bivalirudin group had a 6 x higher risk of acute stent thrombosis (1.1% vs. 0.2%); P=0.007)r
The results of the EUROMAX trial are consistent with those of HORISONS-AMI. The 3 year data of the HORISONS-AMI demonstrated a mortality benefit for the use of bivalirudin.
The EUROMAX trial was not powered to show a mortality benefit. The reduction in major bleeding is probably even more important in countries with a high incidence of HIV. In the last 4 years I am aware of 2 of my patients who received HIV positive blood during CABG (this remains relevant, despite the major bleeding reduction in the trial being non-CABG related).
The increased incidence of acute stent thrombosis reoccured in the EUROMAX trial, despite the early use of aspirin and potent P2Y12 inhibitors.
I agree, that to overcome the increased risk of acute stent thrombosis in patients receiving bivalirudin, they would need to receive more potent IV antiplatet drugs. However, this may increase the major bleeding, and therefor offset the major benefit derived from bivalirudin. At this stage, increased vigilance in the 1st 24hrs post-pci may be prudent practice in patients who have received bivalirudin. One must not forget that there was not an increase in reinfarction, in the bivalirudin group.
Does this trial warrant a change in the guidelines when the cost of bivalirudin is considered. Unfortunately, the countries who would reap most benefit may least be able to afford it, but yes, I do think that that this data should at least influence the guidelines. The 1-year mortality follow up data is eagerly awaited.