麻豆传媒

SAN FRANCISCO -- Jump-starting anticoagulation by initiating bivalirudin (Angiomax) treatment in the ambulance significantly reduced major bleeding and/or death at 30 days in ST-elevation MI (STEMI) patients undergoing primary PCI, but the cost was an increased risk of acute stent thrombosis, researchers reported here.

"The results were very robust," said , director of the coronary care unit at Hôpital Bichat in Paris, noting that there was more than a 3% absolute reduction in the risk of major bleeding or death at 30 days (5.1% versus 8.5%, RR 0.60, 95% CI 0.43-0.82, P=0.001).

But, "risk of acute stent thrombosis was 1.1% versus 0.2%," he said. That worked out to a six times greater relative risk (95% CI 1.37-27.24, P=0.007).

Steg reported results from the EUROMAX trial at a late-breaking clinical trials session at the ; the study was simultaneously published online by The New England Journal of Medicine.

For the secondary triple outcome measure -- death, reinfarction, or non-CABG major bleeding -- bivalirudin also demonstrated superiority, 6.6% versus 9.2% (RR 0.72, 95% CI 0.54-0.96, P=0.02), a result that was driven by a reduction in major bleeding, 2.6% versus 6.0% (RR 0.43, 95% CI 0.28-0.66 P<0.001).

The EUROMAX study "has the potential to change practice" by demonstrating not only the benefit of bivalirudin, but also the safety and efficacy of initiating therapy in the ambulance, said , of the Mayo Clinic in Rochester, Minn.

But, Gersh said, in the U.S. there are "too many barriers to doing this." Asked how those barriers could be overcome, Gersh said a national healthcare system would solve the problem, but he acknowledged that that was an unpopular position.

Steg said the trial was "not without its shortcomings," including its open label design, something that he said was necessitated by the difficulties in "conducting a trial like this in nine European countries." Also, he noted, trial registration was slow, which led the investigators to change the endpoints after the trial had begun.

"The triple endpoint of death, reinfarction, or major bleeding was the original primary endpoint, while death and major bleeding at 30 days was the secondary endpoint," he said. Making that change allowed them to reduce the sample size.

Steg also cautioned that the trial was not powered to show a mortality benefit, although "we will be following patients out for a year to look at mortality, but that will be a post hoc analysis."

, told 麻豆传媒 that the study did confirm the bivalirudin benefit earlier reported by the HORIZONS-AMI investigators "in a more contemporary milieu."

For example, roughly half of the 2,218 STEMI patients in EUROMAX underwent radial access PCI and the use of glycoprotein IIb/IIIa inhibitors was left to the discretion of the treating physician. Likewise, in the bivalirudin arm, physicians had the option of continuing high dose bivalirudin after stenting.

The average age of patients was 61 and about 25% were women.

Patients in the bivalirudin arm were given a bolus of 0.75 mg/k followed by infusion (1.75 mg/k/hour) during transport.

The protocol specified that the infusion should be continued for at least 4 hours after PCI at 0.25 mg/k/h, but continuing the higher dose was optional, Steg said.

Comment