WASHINGTON – Unfractionated heparin outperformed bivalirudin for 28-day outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in a single-center randomized trial of more than 1,800 patients when use of a glycoprotein IIb/IIIa inhibitor was kept to a minimum.
Use of unfractionated heparin (UFH) compared with bivalirudin (Angiomax) led to a significant reduction in the rate of combined major adverse coronary events after 28 days compared with bivalirudin driven primarily by a significant cut in the rate of acute stent thrombosis and repeat myocardial infarctions with no increased risk for major bleeding events, consistent results across all subgroups examined, and the potential for substantial savings in drug costs, Dr. Adeel Shahzad said at the annual meeting of the American College of Cardiology.
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Dr. Rod Stables
The combined rate of major adverse coronary events was 6% in patients treated with UFH and 9% in those treated with bivalirudin, a statistically significant difference for the study’s primary efficacy endpoint. The rate of major bleeding events, the study’s primary safety endpoint, occurred in 3.5% of patients treated with bivalirudin and in 3.1% of those who received UFH, a difference that was not statistically significant.
The superior outcome with UFH in this study, which contrasted sharply with the results of several prior head-to-head comparisons of the two drugs in patients with a ST-segment elevation myocardial infarction (STEMI) or other acute coronary syndrome events undergoing primary percutaneous coronary intervention (PCI) seemed closely tied to the study’s protocol that restricted coadministration of a glycoprotein IIb/IIIa inhibitor (such as abciximab [ReoPro]) to only those patients experiencing thrombotic complications during PCI ("bailout" use).
"For the first time, unfractionated heparin was used like bivalirudin," with low use of a glycoprotein IIb/IIIa inhibitor, noted the study’s principal investigator, Dr. Rod Stables, director of the cardiac catheterization laboratory at Liverpool (England) Heart and Chest Hospital.
Current STEMI management guidelines from the American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2013;61:e78-140) and from the European Society of Cardiology (Eur. Heart J. 2012;33:2569-619) endorse use of either bivalirudin or UFH as an anticoagulant when patients undergo primary PCI. The European guidelines say that bivalirudin is preferred over UFH when a glycoprotein IIb/IIIa antagonist is administered along with UFH.
"It’s perfectly legitimate with the guidelines to use unfractionated heparin, but most people [in the United States] use bivalirudin or a glycoprotein IIb/IIIa inhibitor with heparin," said Dr. Spencer B. King III, an interventional cardiologist at St. Joseph’s Health System in Atlanta.
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Dr. David R. Holmes, Jr.
Based on the new results, "people will say it’s really interesting, and they may at least think about not using bivalirudin all the time," said Dr. David R. Holmes Jr., an interventional cardiologist and professor of medicine at the Mayo Clinic in Rochester, Minn. "Those who are believers in bivalirudin will continue to use it, but others will say that heparin did just fine [in this trial] and is less expensive.
Dr. Stables predicted that based on these results, interventionalists at his institution who can choose between bivalirudin and UFH will increasingly use heparin, a change that he estimated could save his hospital as much as 500,000 pounds per year (about $800,000).
The HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary PCI) trial randomized 1,829 STEMI patients at Liverpool Heart and Chest Hospital during February 2012–November 2013. The data analysis included the 1,812 patients from the series who agreed to participate in the study, which had a delayed-consent design (see sidebar). A total of 1,917 patients with STEMI presented at Liverpool during this 22-month period, with about 5% of patients excluded because of prespecified exclusion criteria. This produced a highly representative, "real-world" population. "It’s the closest you can get to an all-comers trial," Dr. Stables said.
About 62% of the patients received ticagrelor (Brilinta) as an antiplatelet drug, about 27% received prasugrel (Effient), and the remaining 11% received clopidogrel. About 14% of the bivalirudin-treated patients and about 16% of those randomized to receive UFH were treated with a glycoprotein IIb/IIIa inhibitor. The door-to-balloon time for patients in the study averaged 29 minutes, and the average age of the patients was 63 years. About 81% of patients underwent coronary catheterization by radial-artery access, with the remainder undergoing femoral-artery access; about 82% of all patients had a PCI procedure actually performed. And of those who underwent primary PCI, about 92% of all patients received at least one coronary stent. The 907 consenting patients randomized to UFH received a dose of 70 units/kg prior to catheterization. The 905 consenting patients randomized to bivalirudin received a 0.75-mg/kg bolus and a 1.75-mg/kg/hour infusion during their procedure.