PARIS – Heparin treatment may produce survival rates that rival those seen in treatment with bivalirudin in patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, based on analysis of data from more than 40,000 patients collected in a nationwide Swedish registry.
The new finding “questions the superiority of bivalirudin over heparin in the absence of glycoprotein IIb/IIIa blockade” in these patients and produced some doubt about the need for the extra expense of using bivalirudin (Angiomax) to treat these patients, Dr. Oskar Angerås said at the annual meeting of the European Association of Percutaneous Coronary Interventions. The finding prompted him recently to shift his practice and treat non–ST-elevation acute coronary syndrome (NSTE-ACS) with heparin rather than bivalirudin when performing percutaneous coronary intervention (PCI), he said in an interview. It also led him and his associates to plan to soon start a randomized, controlled trial to compare the two treatment options in about 6,000 Swedish patients, a study he hopes will definitely address this issue.
Mitchel L. Zoler/IMNG Medical Media
Dr. Oskar Angerås
Bivalirudin was the highest-rated anticoagulant for use during PCI in the most recent, 2011 guidelines of American College of Cardiology and American Heart Association (J. Am. Coll. Cardiol. 2011;58:e44-e122), while the European Society of Cardiology’s most recent guidelines on managing patients with NTSE-ACS rated fondaparinux (Arixtra) as the top anticoagulant and put bivalirudin, unfractionated heparin, and low-molecular-weight heparin on equal footing a step below fondaparinux (Eur. Heart J. 2011;32:2999-305zz4).
The role of bivalirudin in this setting largely stems from results of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial (N. Engl. J. Med. 2006;355:2203-16), but the trial has reduced relevance today because of several changes in practice since then, said Dr. Angerås , an interventional cardiologist at Sahlgrenska University Hospital in Gothenburg, Sweden. In ACUITY, all patients received a glycoprotein IIb/IIIa inhibitor, a drug class now infrequently used in these patients. Fewer than 60% of ACUITY patients underwent PCI, fewer than 60% were biomarker positive, and among those who did receive a coronary stent only 6% had their intervention done via radial-artery access, “quite different from our daily practice” today, he said.
Two other published studies also compared bivalirudin and heparin, the Hirulog Angioplasty Study (N. Engl. J. Med. 1995;333:764-9), and the Intracoronary Stenting and Antithrombosis Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial (N. Engl. J. Med. 2008;359:688-96), but both of those studies only found a difference in bleeding complications in favor of bivalirudin, but no mortality difference between the drugs, he noted.
To assess the impact of the two alternatives on patient survival in more contemporary practice, Dr. Angerås and his associates 41,537 consecutive NSTE-ACS patients who underwent PCI without use of a glycoprotein IIb/IIIa inhibitor at any of the 28 Swedish centers that participate in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) during 2006-2011. The patients averaged about 68 years of age, about 75% were biomarker positive, and about 47% underwent PCI using a radial-artery approach. Nearly 27,000 of these patients received heparin, either in the unfractionated or low-molecular weight form, and about 8,700 received bivalirudin. Data on anticoagulant use were not available for about 6,000 patients.
Among the roughly 35,000 patients with known anticoagulant treatment, those who received bivalirudin had a statistically significant 50% increased 30-day mortality rate, compared with those who receive heparin. After the researchers did a series of statistical adjustments to control for both known and unknown confounders, the mortality rates in the heparin and bivalirudin subgroups became roughly similar, without a statistically significant difference, Dr. Angerås reported. The researchers saw similar mortality rates, regardless of the anticoagulant used; the patient’s age, sex, PCI access site; or the presence or absence of diabetes. The registry data also showed no statistically significant difference in bleeding episodes between the heparin- and bivalirudin-treated patients, but Dr. Angerås said that information on bleeding was not available for all of the years included in the analysis.
Patients who receive heparin and bivalirudin “are two different groups,” commented Dr. Andreas Baumbach, an interventional cardiologist at the Bristol (England) Heart Institute and designated discussant for the study. “It’s no surprise to me that in the group that I would consider to have higher risk,” the patients who received bivalirudin “had more endpoints. When you do all the statistical analysis and make the two groups equal by risk, then you see no difference.”
Dr. Angerås agreed. “We are very cautious about our conclusion,” and he stressed that the issue will not be clearly settled until results from the randomized, controlled study are available.