The difference in rates of major adverse coronary events during the 28-day follow-up seemed driven primarily by a difference in the rate of myocardial infarctions, which occurred in 2.3% of the bivalirudin patients and in 0.8% of the UFH patients, Dr. Shahzad said. The rate of acute stent thrombosis was 2.9% in the bivalirudin arm and 0.9% in patients on UFH.
Several prior trials that compared UFH and bivalirudin in STEMI or acute coronary syndrome patients undergoing PCI or other invasive procedures used either mandatory coadministration of a glycoprotein IIb/IIIa inhibitor along with UHF, or a much higher rate of discretionary use, such as in the ACUITY (N. Engl. J. Med. 2006;355:2203-16), HORIZONS (N. Engl. J. Med. 2008;358:2218-30), and EUROMAX (N. Engl. J. Med. 2013;369:2207-17) studies. In all these trials, the rates of major bleeding events were significantly higher in the UFH arm, and this appeared to lead to an increased number of adverse coronary events during the first month following intervention.
"What we’ve seen in every trial before was a reduction in bleeding complications of about 40% to 50%. The National Cardiovascular Data Registry shows a tremendous decrease [in bleeding] when you change from heparin to bivalirudin," said Dr. Roxana Mehran, an interventional cardiologist and professor of medicine at Mount Sinai Hospital in New York.
"All the trials had differential use of glycoprotein IIb/IIIa inhibitors" in the UFH and bivalirudin arms, noted Dr. Shahzad, an interventional cardiologist at Liverpool Heart and Chest Hospital.
Dr. Stables said that the low bleeding rates with UFH in the new study seemed largely dependent on the relatively low rate at which patients received a glycoprotein IIb/IIIa inhibitor and did not correlate with radial-artery access. "We did a prespecified subgroup analysis of patients who underwent radial or femoral access and the outcomes were the same in both groups," he said.
Dr. Gregg W. Stone, who served as lead investigator for ACUITY and HORIZONS, contended that the trialists in HEAT-PPCI underdosed bivalirudin based on the average activated clotting time (ACT) of 270 seconds in the bivalirudin-treated patients in the study. Most patients properly treated with bivalirudin achieve ACTs of 350-450 seconds, said Dr. Stone, professor of medicine and director of cardiovascular research and education at Columbia University in New York. Dr. Stone also noted that the "results of this single-center study were markedly different from three randomized, controlled trials done at 250 centers and involving more than 8,000 patients."
Dr. Shahzad countered that the ACT-measuring device used at his institution was consistently accurate but measures ACT levels that are typically 50 seconds below values obtained with most other devices.
HEAT-PPCI did not receive any commercial funding. Dr. Shahzad, Dr. Stables, Dr. King, and Dr. Holmes had no disclosures. Dr. Mehran has received consultant fees, honoraria, and/or research grants from 10 drug and device companies, but not from The Medicines Company, which markets Angiomax. Dr. Stone has grants or fees from, or has an ownership position in, several drug or device companies, but not The Medicines Company.
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