EUROMAX: Prehospital Bivalirudin Reduces Bleeding in STEMI

San Francisco, CA—Results of the randomized EUROMAX trial show that administering bivalirudin to STEMI patients en route to the hospital for primary PCI reduces the primary outcome of short-term death and major non-CABG bleeding compared with heparin plus optional use of a glycoprotein IIb/IIIa inhibitor (GPI). The finding, presented by Philippe Gabriel Steg, MD, of Hôpital Bichat, Assistance Publique-Hôpitaux de Paris in France and simultaneously published in the New England Journal of Medicine, was driven primarily by a dramatic decrease in major bleeding.  

Researchers at 65 European centers randomized 2,218 STEMI patients who were being transported for primary PCI to bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg/h infusion; or unfractionated heparin or enoxaparin (standard practice) with optional GPIs. 

At 30 days, bivalirudin reduced the rate of the primary endpoint of death or non-CABG-related major bleeding by 40% as well as the principal secondary endpoint of death, reinfarction, and major bleeding by about 25%. Most notably, the individual endpoint of major bleeding was decreased by approximately 60%. However, no difference was seen in all-cause or cardiac death, although the trial was underpowered for these endpoints (see Figure). 

However, bivalirudin did increase the risk of definite stent thrombosis compared with heparin (1.6% vs. 0.5%; P=.02).

The bivalirudin strategy was favored across 12 prespecified subgroups. There were no interactions with procedural or clinical variables including age, sex, diabetes, access site, stent type, P2Y12 loading or maintenance dose, or baseline creatinine clearance. 

According to Steg, follow-up will continue for 1 year to see if the bleeding reduction ultimately translates into a mortality benefit. Importantly, he noted, the current results were achieved against the background of contemporary care, characterized by a high rate of radial access, use of novel P2Y12 inhibitors, and optional use of GPIs in the control arm. 

Commenting on the trial, TCT Course Co-Director Gregg W. Stone, MD, of Columbia University Medical Center in New York, N.Y., observed that despite many differences in protocol, the findings from EUROMAX are consistent with those from HORIZONS-AMI. But he added that whether starting bivalirudin in the ambulance is preferable to waiting until the patient reaches the cath lab, as was done in HORIZONS-AMI, is unknown. 

A key finding, Stone observed, is that the advantage with bivalirudin was seen in patients undergoing radial as well as femoral intervention. 

“Acute stent thrombosis, typically occurring within hours of PCI, while rarely fatal, is the only troubling issue of bivalirudin in STEMI,” Stone said. “We need strategies to reduce this complication. From the EUROMAX data shown thus far, it’s not obvious that the availability of prasugrel or ticagrelor, or prolonged bivalirudin infusion is the answer to this problem. Additional studies are warranted to determine whether rapid-acting, potent IV cangrelor is the solution to this concern.”

In a press conference, Bernard Gersh, MD, of the Mayo Clinic in Rochester, Minn., predicted that these results will change STEMI practice. However, he added, because of the competitive system of care in the United States, the barriers to implementation are large. 

Disclosures:

EUROMAX was supported by The Medicines Company.

Steg reports receiving research grants from the New York University School of Medicine, Sanofi and Servier; consultant/speaking fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim. Bristol-Myers Squibb, Daiichi-Sankyo, Glaxo-SmithKline, Eli Lilly, Medtronic CardioVascular, Novartis, Otsuka, Pfizer, Sanofi, Servier, The Medicines Company and Vivus; and holding stock in Aterovax. 

Stone reports receiving consultant fees and having equity relationships with multiple pharmaceutical and device companies. 

Gersh reports receiving research and consulting fees from multiple pharmaceutical and device companies.