ABSTRACT
PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function. METHODS: Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation. RESULTS: Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold. CONCLUSIONS: COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/administration & dosage , Blood Platelets/drug effects , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Blood Platelets/enzymology , Cross-Over Studies , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Drug Administration Schedule , Drug Interactions , Etoricoxib , Female , Humans , Ibuprofen/adverse effects , Male , Meloxicam , Middle Aged , Naproxen/adverse effects , Netherlands , Platelet Function Tests , Prospective Studies , Pyridines/adverse effects , Risk Assessment , Sulfones/adverse effects , Thiazines/adverse effects , Thiazoles/adverse effects , Time Factors , Young AdultABSTRACT
We present the case of a 75-year-old woman with a medical history of rheumatoid arthritis treated with hydroxychloroquine, who was admitted with acute left-sided heart failure due to a hydroxychloroquine-induced cardiomyopathy as supported by endomyocardial biopsy.