ISAR-REACT 4: Outcomes Similar for Bivalirudin vs. Abciximab-Heparin Combo

Kastrati A. N Eng J Med.2011;doi:10.1056/NEJMoa1109596.

Issue: January/February 2012

ORLANDO, Fla. — Abciximab plus heparin and bivalirudin were associated with similar rates of death, subsequent MI or need for further revascularization in patients with non-STEMI undergoing PCI, according to a late-breaking trial presented at the American Heart Association Scientific Sessions.

In the double blind ISAR-REACT 4 trial, patients with acute non-STEMI (n=1,721) were assigned either abciximab (ReoPro, Centocor and Eli Lilly) plus unfractionated heparin (n=861) or bivalirudin (Angiomax, The Medicines Company; n=860).

Among patients assigned abciximab, 10.9% experienced the primary composite endpoint of death, large recurrent MI, urgent target vessel revascularization or major bleeding at 30 days vs. 11% of patients assigned to bivalirudin (RR=0.99; 95% CI, 0.74-1.32). The secondary endpoint of efficacy in death, any recurrent MI or urgent TVR was also similar with the dual therapy (12.8%) compared with bivalirudin (13.4%; RR=0.96; 95% CI, 0.74-1.25).


	Adnan Kastrati

Furthermore, patients taking the abciximab-heparin combination were more likely to experience major bleeding than those taking bivalirudin (4.6% vs. 2.6%; RR=1.84; 95% CI, 1.10-3.07).

“These findings … show that bivalirudin might be the preferred drug in patients undergoing PCI for an acute MI, with or without ST-segment elevation,” Adnan Kastrati, MD, professor of interventional cardiology at Technische Universitat, Munich, Germany, and trial investigator, said at a press conference. – by Casey Murphy

Disclosure:Dr. Kastrati reports receiving speaker fees and honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, Cordia, Daiichi Sankyo/Eli Lilly and Medtronic.

Deepak L. Bhatt

ISAR-REACT 4 was a rigorous, double blind, double-dummy trial. The comparison was against abciximab, which some still consider ‘the gold standard’ glycoprotein IIb/IIIa inhibitor. The trial also used a strict definition of bleeding — intracranial bleeding, intraocular bleeding or retroperitoneal bleeding, a hemoglobin decrease greater than four plus either overt bleeding or the need for transfusion of two or more units; it’s difficult to argue with the importance of this very strict definition of bleeding.

Some caveats in terms of interpreting this trial: Patients were pretreated with aspirin and 600 mg clopidogrel (Plavix, Sanofi-Aventis), so the results may not apply to patients who are not treated with both aspirin and clopidogrel; prasugrel (Effient, Eli Lilly) and ticagrelor (Brilinta, AstraZeneca), two newer oral antiplatelet agents, were not used, though it’s difficult for me to see how this would change the results; and the bleeding advantage observed may have been attenuated if more radial access cases had been done, but nevertheless, there were still numerically lower pericardial bleeds, gastrointestinal bleeds and no apparent loss of efficacy for bivalirudin vs. abciximab plus unfractionated heparin.

Coupled with data from the HORIZONS-AMI trial, which showed a significantly lower mortality with bivalirudin than with heparin plus glycoprotein IIb/IIIa inhibitors, these data from ISAR-REACT 4 support the use of bivalirudin during PCI across the full spectrum of ACS.

– Deepak L. Bhatt, MD, MPH
Cardiology Today Intervention Chief Medical Editor
Disclosure: Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis and The Medicines Company.