Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials

PURPOSE: The major risk of therapy with platelet glycoprotein IIb/IIIa receptor inhibitors is bleeding. We reviewed trials using these agents to determine if bleeding risks include an increased incidence of intracranial hemorrhage. METHODS: A Medline search identified 14 randomized trials of intravenous platelet glycoprotein IIb/IIIa receptor inhibitors for patients undergoing percutaneous coronary intervention or who had an acute coronary syndrome. We compared the incidence of intracranial hemorrhage among 15,850 patients treated with glycoprotein IIb/IIIa inhibitors with that among 12,039 patients treated with placebo. RESULTS: The incidence of intracranial hemorrhage with heparin plus any IIb/IIIa inhibitor was similar to placebo with heparin (0.12% vs 0.09%, odds ratio = 1.3, 95% confidence interval: 0.6 to 3.1, P = 0.59). The incidence of intracranial hemorrhage with glycoprotein IIb/IIIa drugs alone was similar to that with heparin alone (0.07% vs 0.06%), albeit with a wide confidence interval (odds ratio = 1.2, 95% confidence interval: 0.1 to 16, P = 1.0). CONCLUSIONS: Intravenous glycoprotein IIb/IIIa receptor inhibitors alone or in combination with heparin do not cause a statistically significant excess of intracranial hemorrhage as compared with heparin alone. Because of small numbers, the data do not exclude the possibility of an excess of intracranial hemorrhage in some groups of patients treated with glycoprotein IIb/IIIa receptor inhibitors.