TCT: Bivalirudin (Angiomax) Effective in Primary PCI for STEMI

WASHINGTON, Oct. 24 -- Bivalirudin (Angiomax) as monotherapy saved lives and significantly reduced major bleeding at 30 days in patients with ST-elevation myocardial infarction undergoing primary stenting, investigators reported here.The direct thrombin inhibitor was compared with a standard anti-coagulation therapy of a glycoprotein IIb/IIIa inhibitor (abciximab) plus unfractionated heparin, Gregg W. Stone, M.D., of Columbia University, told a packed house at the Transcatheter Cardiovascular Therapeutics late-breaking clinical trials plenary today.
At 30 days in the HORIZONS AMI trial, the rate of net adverse clinical events was 12.1% in the control arm versus 9.2% in the bivalirudin monotherapy arm (P=0.006), Dr. Stone said. The cardiac mortality was 1.8% in the bivalirudin arm versus 2.9% in the abciximab plus heparin arm (P=0.035), and the major bleeding rate was 4.9% versus 8.3% in the control arm (P£0.0001).
Overall mortality was 2.1% in the bivalirudin group versus 3.1% in the control arm, but overall mortality eluded statistical significance (P=0.058).
During a press conference, Dr. Stone said there was "no question of non-inferiority here -- bivalirudin was clearly superior."
Marc Cohen, M.D., of Mount Sinai Medical School and chief of interventional cardiology at Newark Beth Israel Hospital, who was not involved in the HORIZONS trial, did not agree.
In an interview, he said the data suggest that bivalirudin may be a good option for some "low risk, uncomplicated STEMI patients," but there were some disturbing signals.
For example, "the stent thrombosis rate within 24 hours of procedure was 0.3% in the GP IIb/IIIa/heparin arm versus 1.3% in the bivalirudin arm and that was significant at P=0.0009," Dr. Cohen said.
Likewise the ischemic target vessel revascularization rate of 1.9% in the control arm versus 2.6% in the bivalirudin arm "while not a statistically significant difference, was headed in the wrong way," Dr. Cohen said.
But Dr. Cohen was in the minority as Dr. Stone's presentation was greeted with enthusiastic applause and the discussant, Michael Bertrand, M.D., of the University of Lille in Lambersart, France, emphasized the positive findings of the trial in his critique.
"And I think it was surprising to see a reduction in cardiac death in a trial with these small numbers," Dr. Bertrand said during a press conference. "That is important."
Christopher Cannon, M.D., of Brigham and Women's Hospital and Harvard Medical School, was similarly impressed. "It had less bleeding and interestingly this seemed to translate into fewer cardiac deaths," he said.
Because bleeding risk is a major concern during interventions "it seems that bivalirudin would be a good choice for patients where bleeding is a concern," Dr. Cannon said in an interview. Dr. Cannon was not involved in the study.
The trial recruited 3,602 patients with symptomatic STEMI who were randomized in less than 12 hours from symptom onset. All patients were started on dual antiplatelet therapy and randomized in the emergency department to either unfractionated heparin plus abciximab (ReoPro) or eptifibatide (Integrilin) plus unfractionated heparin (n=1,800) or bivalirudin.
The 30-day follow-up data were complete on 1,778 controls and 1,777 bivalirudin patients, but analysis was based on intention to treat.
The 30-day results, Dr. Stone emphasized, are just the first installment from the HORIZONS AMI story. These pharmacologic results represent "a strategy trial," he said. After angiography, patients were referred for coronary artery bypass surgery (2.2% in the control arm and 1.3% in the bivalirudin group), medical management (5.4% in the control group and 5.2% in the bivalirudin group) or percutaneous coronary intervention (92.2% of controls and 93.2% of bivalirudin patients).
Three thousand of the patients went on to stenting and were randomized to either bare-metal stents or paclitaxel-eluting (Taxus) stents. The results of that second phase are not yet known, Dr. Stone said.
The primary 30-day endpoint was net adverse clinical events and major bleeding, which was defined as intracranial bleeding, intraocular bleeding, retroperitoneal bleeding, access site bleeding requiring surgery, hematoma ≥ 5 cm, blood product transfusion, reoperation for bleeding, Hgb↓≥3 g/dL with an overt source, and Hgb↓≥ 4 g/dL without an overt source.
The HORIZONS AMI trial was funded by the Medicines Company and Boston Scientific via unrestricted educational grants to the Cardiovascular Research Foundation, which Dr. Stone said maintained complete control over the study design and data. Dr. Stone disclosed research support from The Medicines Company and Boston Scientific and honoraria from Pfizer. Dr. Cohen disclosed support from Sanofi-Aventis, Schering-Plough, Bristol-Myers Squibb, and "some funding from The Medicines Company". Dr. Cannon disclosed support from Merck, Schering-Plough, AstraZeneca, GlaxoSmithKline, and Bristol-Myers Squibb.Primary source: Transcatheter Cardiovascular TherapeuticsSource reference: Stone, GW et al "HORIZONS AMI A Prospective, Randomized Comparison of Bivalirudin vs. Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Primary Angioplasty in Acute Myocardial Infarction 30 Day Results" Late Breaking Clinical Trials