ArticlesPlatelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials
Introduction
Disruption of atherosclerotic plaque, which either occurs spontaneously in patients with acute coronary syndromes or during a percutaneous coronary intervention (PCI), triggers platelet aggregation and intracoronary thrombus formation, and can result in myocardial infarction or death. Activation of the platelet glycoprotein IIb/IIIa receptor is the final common pathway in the process leading to platelet aggregation, and inhibitors of this receptor have been shown to protect against periprocedural death or myocardial infarction in patients undergoing PCI for various indications.1, 2, 3, 4
Randomised clinical trials have indicated that glycoprotein IIb/IIIa inhibitors reduce the occurrence of these events by 38% compared with placebo or control therapy.5, 6 However, the results of trials in acute coronary syndromes in which coronary revascularisation during study-drug infusion was not part of the protocol, have been less conclusive. Glycoprotein IIb/IIIa inhibitors did reduce cardiac endpoints in most of these trials,7, 8, 9, 10, 11 but not in all.12 In the trials with a positive trend, the event reduction was often lower than expected, and significance was not always reached. In fact, most trials in acute coronary syndromes were powered for the detection of a large treatment effect (>20% risk reduction), but were underpowered for more modest, but potentially clinically important, effects. In this situation, a meta-analysis of the combined trial data can be useful to estimate more reliably the overall effect of glycoprotein IIb/IIIa inhibitors. If based on data from individual patients, such meta-analyses can also provide reliable estimates of treatment effects in clinically meaningful subgroups of patients.13 In case of an overall beneficial effect, analysis of subgroups can help identify the target population to be treated preferentially. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled for early coronary revascularisation.
Section snippets
Methods
The methodological principles that lie behind a meta-analysis of randomised clinical trials based on data from individual patients have been described in detail.13 We therefore only briefly describe the applied methods of trial selection, data-management, endpoint definitions, and statistical analysis.
Patients' characteristics
The six trials altogether enrolled 31402 patients in 41 countries. There were no important differences in baseline characteristics between patients randomly assigned glycoprotein IIb/IIIa inhibitors (n=18297) and those assigned placebo or control (n=13105). The mean age of the population was 64 years, 65% were men, and 76% had a history of cardiovascular disease. 56% of the patients presented with ST-segment depression, 46% with raised creatine kinase MB concentrations, and 80% with either one
Discussion
Inhibitors of the platelet glycoprotein IIb/IIIa receptor were associated with an absolute reduction in the 30-day rate of death or myocardial infarction of 1% compared with control therapy. This risk reduction was achieved after completion of study medication, and was maintained throughout 30-day follow-up. The treatment benefit was seen in patients treated with and without heparin. Sex differences were apparent, with a treatment benefit in men (two-thirds of the population), but not in women.
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