CURE 2001.

Methods	Randomized controlled trial.
Participants	12,562 people with acute coronary syndromes without ST‐segment elevation.
Interventions	Clopidogrel loading dose 300 mg followed by 75 mg daily plus aspirin 75‐325 mg daily (n = 6259) for 3‐12 months. Placebo plus aspirin 75‐325 mg daily (n = 6303) for 3‐12 months.
Outcomes	Primary outcomes: composite of death from cardiovascular causes, non‐fatal MI or stroke; composite of the first primary outcome or refractory ischaemia. Secondary outcomes: severe ischaemia, heart failure and need for revascularization. Safety‐related outcomes: bleeding complications, categorized as life‐threatening, major (≥ 2 units of blood), or minor.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were randomly assigned to either the clopidogrel group or the placebo group by a central, 24‐hour, computerized randomization service. Permuted‐block randomization, stratified according to clinical center, was used."
Allocation concealment (selection bias)	Low risk	"Patients were randomly assigned to either the clopidogrel group or the placebo group by a central, 24‐hour, computerized randomization service. Permuted‐block randomization, stratified according to clinical center, was used."
Blinding (performance bias and detection bias) All outcomes	Low risk	"We undertook a randomized, double‐blind, placebo‐controlled trial ..."
Incomplete outcome data (attrition bias) All outcomes	Low risk	"All unrefuted events that occurred up to the end of the scheduled follow‐up period on December 6, 2000, are included in the analyses. Vital status was ascertained for 12,549 of the 12,562 patients who underwent randomization (99.9 percent), with 6 patients in the clopidogrel group and 7 in the placebo group lost to follow‐up ... A total of 21.1 percent of the patients in the clopidogrel group discontinued the study medication permanently, as compared with 18.8 percent in the placebo group."
Selective reporting (reporting bias)	Low risk	Outcomes reported as per protocol.
Other bias	High risk	Pharmaceutical industry funded.