BACKGROUND: More than 30 randomized trials involving more than 40, 000 patients with acute coronary syndrome and undergoing percutaneous coronary intervention have evaluated the efficacy and safety of direct thrombin inhibitors relative to unfractionated heparin. However, few trials have been large enough to provide reliable estimates of treatment effects on major cardiovascular outcomes. Therefore uncertainty remains regarding the benefits of direct thrombin inhibitors on major cardiovascular outcomes such as death or myocardial infarction and the balance of any such benefits against the risk of major bleeding. OBJECTIVES: By combining data on individual patients from all the major studies, we sought to obtain reliable estimates of the treatment effects of direct thrombin inhibitors on death, myocardial infarction, major bleeding, and secondary outcomes including refractory or recurrent ischemia and need for revascularization. We examined these outcomes at the completion of active treatment and during long-term follow-up, as well as in clinically important subgroups. METHODS: Individual patient data, including baseline demographics, previous history of vascular disease, conventional vascular risk factors, qualifying diagnosis, prognostic markers including biochemical markers of extent of myocardial injury, cointerventions, and fatal and nonfatal cardiovascular outcomes, have been obtained from 14 randomized studies, constituting more than 95% of the available randomized evidence. These data will undergo exhaustive data checking for completeness and consistency and will then be merged into a master database for analysis. Analyses will undergo extensive scrutiny by trialists of the direct thrombin inhibitor studies before incorporation into a manuscript.
BACKGROUND: More than 30 randomized trials involving more than 40, 000 patients with acute coronary syndrome and undergoing percutaneous coronary intervention have evaluated the efficacy and safety of direct thrombin inhibitors relative to unfractionated heparin. However, few trials have been large enough to provide reliable estimates of treatment effects on major cardiovascular outcomes. Therefore uncertainty remains regarding the benefits of direct thrombin inhibitors on major cardiovascular outcomes such as death or myocardial infarction and the balance of any such benefits against the risk of major bleeding. OBJECTIVES: By combining data on individual patients from all the major studies, we sought to obtain reliable estimates of the treatment effects of direct thrombin inhibitors on death, myocardial infarction, major bleeding, and secondary outcomes including refractory or recurrent ischemia and need for revascularization. We examined these outcomes at the completion of active treatment and during long-term follow-up, as well as in clinically important subgroups. METHODS: Individual patient data, including baseline demographics, previous history of vascular disease, conventional vascular risk factors, qualifying diagnosis, prognostic markers including biochemical markers of extent of myocardial injury, cointerventions, and fatal and nonfatal cardiovascular outcomes, have been obtained from 14 randomized studies, constituting more than 95% of the available randomized evidence. These data will undergo exhaustive data checking for completeness and consistency and will then be merged into a master database for analysis. Analyses will undergo extensive scrutiny by trialists of the direct thrombin inhibitor studies before incorporation into a manuscript.