PROCLAIM: pilot study to examine the effects of clopidogrel on inflammatory markers in patients with metabolic syndrome receiving low-dose aspirin.
Metabolic syndrome is associated with intravascular inflammation, as determined by increased levels of inflammatory biomarkers and an increased risk of ischemic atherothrombotic events. Evidence suggests that atherothrombosis and intravascular inflammation share predictive biomarkers, including high-sensitivity C-reactive protein, CD40 ligand, P-selectin, and N-terminal pro-brain natriuretic peptide. Patients who had metabolic syndrome were randomized to receive clopidogrel 75 mg/day plus aspirin 81 mg/day (n = 89) or placebo plus aspirin 81 mg/day (n = 92) for 9 weeks to assess the efficacy of each treatment in suppression of inflammatory markers. 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 was assessed to evaluate each treatment. There was a significant difference at Week 6 in model-adjusted CD40-ligand levels in favor of clopidogrel plus aspirin compared with placebo plus aspirin in both the intent-to-treat population (difference between least-squares means = -186.5; 95% confidence interval, -342.3 to -30.8; P = 0.02) and the per-protocol population (P = 0.05). No significant differences were observed between the treatment arms for high-sensitivity C-reactive protein, P-selectin, and N-terminal pro-brain natriuretic peptide. There were no deaths or serious adverse events in either treatment arm. Data from this study suggest that clopidogrel can decrease the expression of the CD40-ligand biomarker.
Willerson
James T
JT
Cullen Cardiovascular Research Laboratories, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030, USA. jwillerson@heart.thi.tmc.edu
Cable
Greg
G
Yeh
Edward T H
ET
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D050197:Atherosclerosis / Q000276:immunology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016018:Least-Squares Analysis; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000276:immunology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D023201:CD40 Ligand; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin