ORLANDO, FL—The direct thrombin inhibitor bivalirudin protects patients with non-ST-elevation acute myocardial infarction (NSTEMI) from severe adverse events as well as a combination of abciximab and unfractionated heparin following percutaneous coronary intervention (PCI) while reducing major bleeding. Building on the results of HORIZONS-AMI, these data suggest that bivalirudin might be the preferred drug for patients undergoing PCI for an acute MI, with or without ST-segment elevation.

The findings were presented in a late breaking clinical trial session November 13, 2011, at the American Heart Association Scientific Sessions.

For ISAR-REACT 4, Adnan Kastrati, MD, of Deutsches Herzzentrum, Technische Universitat (Munich, Germany), and colleagues studied 1,721 patients with NSTEMI who had been pre-treated with 600 mg of clopidogrel prior to PCI. Patients were randomized to 70 U/kg bolus of heparin plus abciximab in a 0.25 mg/kg bolus followed by an infusion of 0.125 µg/kg/min for 12 hours (n = 861) or bivalirudin in a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/hr (n = 860) for the duration of PCI.

Adverse Events Similar at 30 Days

The primary endpoint of severe adverse events (death, any recurrent MI, urgent TVR, or major bleeding) was identical for both groups at 30 days at 10.9% in the abciximab group and 11.0% in the bivalirudin group (RR 0.99; 95% CI 0.74-1.32; P = 0.94).

The cumulative incidence of death, any MI, and urgent TVR was also identical at 12.8% with abciximab and 13.4% with bivalirudin (RR 0.96; 95% CI 0.74-1.25; P = 0.76). The individual component endpoints of death (1.4% with abciximab and 1.6% with bivalirudin), MI (12.0% vs. 11.4%), and any urgent TVR (0.8% vs. 1.3%), were all equivalent between arms. Major bleeding, meanwhile, was more frequent with abciximab (4.7% vs. 2.6%; RR 1.84; 95% CI 1.10-3.07; P = 0.02).

Emerging Clinical Picture for Bivalirudin

The findings of ISAR-REACT 4 add to the growing body of evidence that supports the use of bivalirudin monotherapy instead of combination treatment involving abciximab and heparin in high-risk patients, according to discussant Deepak L. Bhatt, MD, MPH, of Harvard Medical School (Boston, MA).

Dr. Bhatt noted that findings from HORIZONS-AMI were favorable for bivalirudin in STEMI. HORIZONS-AMI was a prospective, open-label, randomized, multicenter trial that compared the direct thrombin inhibitor to heparin plus abciximab in 3,602 patients undergoing primary PCI.

“Coupled with HORIZONS-AMI,” said Dr. Bhatt, “data from ISAR-REACT 4 support use of bivalirudin during PCI across the full spectrum of acute coronary syndromes.”

Dr. Bhatt also noted that “there have been a number of well-done randomized clinical trials that show bivalirudin is similar in efficacy to heparin and a GP IIb/IIIa blocker with less major bleeding, and the different trials have different definitions [of bleeding]. But no one would argue with the definition in ISAR-REACT 4, which was a very rigorous definition of serious bleeding. So I think [ISAR-REACT 4] should be a practice-changing trial among interventional cardiologists.”

In the trial, major bleeding was defined as intracranial, intraocular, or retroperitoneal; Hb decrease >40g/L plus either overt bleeding or need for transfusion of 2 or more units.

Study Details

Patients in the 2 groups had similar demographic characteristics including previous clinical histories of PCI, CABG, and AMI. The same proportion of patients (80.6% in the abciximab group and 79.4% in the bivalirudin group) had multivessel disease. LVEF was also similar (51.5% and 51.3%, respectively).

Vessel involvement was similar in the 2 groups; LAD, LCx, and RCA were most often the targets of intervention. Most patients had complex B2/C lesions (85.2% in the abciximab group and 87.2% in the bivalirudin group) and drug-eluting stents (88.9% and 87.2%, respectively).

Disclosures

• Dr. Kastrati reports receiving speaker fees or honoraria from Abbott, Astra-Zeneca, Bristol-Myers Squibb, Cordis, Daichii Sankyo/Lilly, and Medtronic.
• Dr. Bhatt reports grants from Amarin, Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and the Medicines Company.

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