Cyclooxygenase‐2 selectivity of non‐steroidal anti‐inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident

• Published in: Alimentary pharmacology & therapeutics 2007-04, Vol.25 (8), p.913-924
• Main Authors: ABRAHAM, N. S., EL‐SERAG, H. B., HARTMAN, C., RICHARDSON, P., DESWAL, A.
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Biological and medical sciences; Cardiology. Vascular system; Cohort Studies; Coronary heart disease; Cyclooxygenase 2 Inhibitors - adverse effects; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Heart; Humans; Male; Medical sciences; Myocardial Infarction - chemically induced; Myocardial Infarction - prevention & control; Neurology; Pharmacology. Drug treatments; Risk Factors; Stroke - chemically induced; Stroke - prevention & control; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2007.03292.x

SUMMARY Aim To assess degree of cyclooxygenase‐2 (COX‐2) selectivity of a non‐steroidal anti‐inflammatory drug (NSAID) and risk of myocardial infarction (MI) or cerebrovascular accident (CVA). Methods Prescription fill data were linked to medical records of a merged VA‐Medicare dataset. NSAIDs were categorized by Cox‐2 selectivity. Incidence of CVA and MI within 180 days of index prescription was assessed using Cox‐proportional hazards models adjusted for gender, race, cardiovascular and pharmacological risk factors and propensity for prescription of highly COX‐2 selective NSAIDs. Results Of 384 322 patients (97.5% men and 85.4% white), 79.4% were prescribed a poorly selective, 16.4% a moderately selective and 4.2% a highly selective NSAID. There were 985 incident cases of MI and 586 cases of CVA in >145 870 person‐years. Highly selective agents had the highest rate of MI (12.3 per 1000 person‐years; [95% CI: 12.2–12.3]) and CVA (8.1 per 1000 person‐years; [95% CI: 8.0–8.2]). Periods without NSAID exposure were associated with lowest risk. In adjusted models, highly selective COX‐2 selective NSAIDs were associated with a 61% increase in CVA and a 47% increase in MI, when compared with poorly selective NSAIDs. Conclusions The risk of MI and CVA increases with any NSAID. Highly COX‐2 selective NSAIDs confer the greatest risk.