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BRAVE-3: Abciximab did not reduce infarct size after clopidogrel loading
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CHICAGO – The addition of abciximab to clopidogrel reperfusion therapy in patients undergoing primary percutaneous coronary intervention was not associated with a reduction in infarct size, according to a study.
Researchers from the Value of Abciximab in Patients With Acute MI Undergoing PCI After High Dose Clopidogrel Pretreatment (BRAVE-3) trial sought to assess the efficacy of abciximab (ReoPro, Centocor), a glycoprotein IIb/IIIa inhibitor, on left ventricular infarct size in patients undergoing primary PCI after pretreatment with a 600 mg loading dose of clopidogrel (Plavix, Sanofi Aventis).
“Glycoprotein IIb/IIIa inhibitors may improve the results of primary PCI in acute STEMI,” Julinda Mehilli, MD, associate professor of medicine at Deutches Herzzentrum Technical University in Munich, Germany, said in a presentation at the 57th Annual Scientific Session of the American College of Cardiology. “However, in patients with acute STEMI undergoing primary PCI after pretreatment with a 600 mg loading dose of clopidogrel, the additional use of abciximab is not associated with further reduction in infarct size.”
No reduced infarct
Mehilli and colleagues enrolled 800 patients for the study.
Patients received either abciximab (n=401) or placebo (n=399) in addition to a regimen of 600 mg of clopidogrel, 500 mg of aspirin and a bolus of 5,000 units of unfractionated heparin. Patients were assessed using the SPECT study at five to seven days following randomization. The primary endpoint was final infarct size, and secondary endpoints were death, MI, stroke, urgent target revascularization and minor bleeding complications. Infarct size was calculated as the percent infarct of the left ventricle.
“As for the primary endpoint, we found no differences between both groups,” Mehilli said. “Patients treated with abciximab had a final infarct size of 15.7% of the left ventricle after the intervention, and in patients receiving placebo, a 16.6% infarct size.”
The researchers found no statistically significant differences between the groups even when baseline characteristics were taken into consideration.
“We performed the primary endpoint analysis in different groups according to age, gender, diabetes, infarct localization, time interval from pain onset to admission, time interval from study drug to PCI and time interval from clopidogrel to PCI,” Mehilli said. “Still, we did not find a benefit of abciximab in each of these two groups.” - by Eric Raible
Were there any limitations of BRAVE-3 that should make us still wonder about abciximab’s ability to reduce infarct size? Well, importantly, patients with STEMI symptoms were enrolled at up to 24 hours in this trial. When one looks at efforts to reduce infarct size, you have to ask yourself critically if this is the right patient population. The mean symptom-to-admission time was 3.5 hours, so it was more than 4.5 hours from symptom-to-balloon time. We have learned from the wave-front concept of necrosis — the spreading of necrosis from the subendocardium to the subepicardium — that infarct size in most patients, at least those with no collaterals, is complete after approximately three hours. It may be unreasonable to expect any therapy to reduce infarct size after that time. So, for many of these patients, it may have been a fait accompli.
– Gregg W. Stone, MD
Professor of Medicine, Columbia University College of Physicians and Surgeons
For more information:
- Mehilli J. Pretreatment with a high loading dose of clopidogrel and value of abciximab during primary coronary intervention in patients with acute MI: results of the randomized BRAVE-3 trial. #2404. Presented at: the 57th Annual Scientific Session of the American College of Cardiology; March 29-April 1, 2008; Chicago.