PROCLAIM 2009.

Methods	Randomized controlled trial.
Participants	181 people with metabolic syndrome, an atherothrombotic vascular event or cardiovascular intervention ≥ 6 months earlier, and an hsCRP level 2‐10 mg/L at screening. Diagnostic criteria for metabolic syndrome included having ≥ 3 of the 5 National Cholesterol Education Program criteria for metabolic syndrome: triglycerides ≥ 150 mg/dL, systolic blood pressure ≥ 130 mmHg and diastolic blood pressure > 85 mmHg, fasting blood glucose ≥ 110 mg/dL, waist circumference > 101.6 cm (40 inches) for men and > 88.9 cm (35 inches) for women, and high‐density lipoprotein cholesterol < 40 mg/dL for men and < 50 mg/dL for women.
Interventions	Clopidogrel 75 mg daily plus aspirin 81 mg daily (n = 89; mean age (± SD) 55.9 ± 12 years; range 18.3‐82.4 years; male 43.8%) for 6 weeks. Placebo plus aspirin 81 mg daily (n = 92; mean age (± SD) 56.3 ± 12 years; range 24.4‐32.3 years; male 41.3%) for 6 weeks.
Outcomes	Change from baseline in the levels of high‐sensitivity C‐reactive protein, CD40 ligand, P‐selectin and N‐terminal pro‐brain natriuretic peptide at 6 weeks.
Notes	Enrolment criteria amended after publication of the CHARISMA study (CHARISMA 2006), which showed that asymptomatic people with multiple atherothrombotic risk factors did not benefit from the addition of clopidogrel to aspirin. The amended enrolment criteria allowed only symptomatic people with a history of an atherothrombotic vascular event or a cardiovascular intervention > 6 months earlier to be included. Because enrolment proceeded at an extremely slow pace, a decision was made to terminate enrolment early in the study, at 181 participants instead of the initially estimated 360 participants.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization to the 2 study arms occurred in a 1:1 ratio using permuted blocks of size 4, and subjects were assigned unique identification numbers."
Allocation concealment (selection bias)	Unclear risk	"Eligible patients were randomly assigned to receive blinded treatment."
Blinding (performance bias and detection bias) All outcomes	Low risk	"Eligible patients were randomly assigned to receive blinded treatment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Figure 2 depicted the flow of participants from enrolment to final disposition, including the number and reasons for discontinuation in each group.
Selective reporting (reporting bias)	Unclear risk	No protocol available.
Other bias	High risk	Pharmaceutical industry funded.