Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib

• Published in: Annals of the rheumatic diseases Vol. 66; no. 6; pp. 764 - 770
• Main Authors: Farkouh, M E, Greenberg, J D, Jeger, R V, Ramanathan, K, Verheugt, F W A, Chesebro, J H, Kirshner, H, Hochman, J S, Lay, C L, Ruland, S, Mellein, B, Matchaba, P T, Fuster, V, Abramson, S B
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2007; BMJ; Elsevier Limited; BMJ Group
• Subjects: Aged; anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arthritis; aspirin; Aspirin - adverse effects; Aspirin - therapeutic use; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular and Cerebrovascular Safety Committee; Cardiovascular Diseases - chemically induced; CCSC; confidence interval; coronary disease; COX; COX-2 inhibitors; cyclooxygenase; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Diclofenac - adverse effects; Diclofenac - analogs & derivatives; Diclofenac - therapeutic use; Diseases of the osteoarticular system; Double-Blind Method; Drug Therapy, Combination; Extended Report; Female; hazard ratio; Health risk assessment; Heart attacks; Heart Defects, Congenital - chemically induced; Heart Outcomes Prevention Evaluation; HOPE; Humans; Ibuprofen - adverse effects; Ibuprofen - therapeutic use; Male; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; myocardial infarction; Naproxen - adverse effects; Naproxen - therapeutic use; non-steroidal anti-inflammatory drugs; NSAIDs; Osteoarthritis; Osteoarthritis - drug therapy; Side effects; Studies; TARGET; Therapeutic Arthritis Research and Gastrointestinal Event Trial; VIGOR; Vioxx Gastrointestinal Outcomes Research; Myocardial infarction; Prostaglandin-endoperoxide synthase; Prognosis; Diseases of the osteoarticular system; Cardiovascular disease; Cyclooxygenase 2 inhibitor; Arthritis; Acetylsalicylic acid; Gastrointestinal; Myocardial disease; Vascular disease; Heart disease; Naproxen; Atherosclerosis; Ibuprofen; Arylpropionic acid derivatives; Lumiracoxib; Degenerative disease; Salicylates; Cerebrovascular disease; Human; Heart failure; Nervous system diseases; Stroke; Enzyme; Enzyme inhibitor; Thrombosis; Antiplatelet agent; Cerebral disorder; Non steroidal antiinflammatory agent; Analgesic; Treatment; Central nervous system disease; Arthropathy; Antipyretic; Oxidoreductases; Osteoarthritis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2006.066001

Background: Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs is lacking in patients at high cardiovascular risk who are taking aspirin. Objective: To determine the cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Methods: The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) of 18 325 patients with osteoarthritis comprised two parallel substudies, comparing lumiracoxib (COX-2 inhibitor) with either ibuprofen or naproxen. A post hoc analysis by baseline cardiovascular risk, treatment assignment, and low-dose aspirin use was performed. The primary composite end point was cardiovascular mortality, non-fatal myocardial infarction, and stroke at 1 year; a secondary end point was the development of congestive heart failure (CHF). Results: In high risk patients among aspirin users, patients in the ibuprofen substudy had more primary events with ibuprofen than lumiracoxib (2.14% vs 0.25%, p = 0.038), whereas in the naproxen substudy rates were similar for naproxen and lumiracoxib (1.58% vs 1.48%, p = 0.899). High risk patients not taking aspirin had fewer primary events with naproxen than with lumiracoxib (0% vs 1.57%, p = 0.027), but not for ibuprofen versus lumiracoxib (0.92% vs 0.80%, p = 0.920). Overall, CHF developed more often with ibuprofen than lumiracoxib (1.28% vs 0.14%; p = 0.031), whereas no difference existed between naproxen and lumiracoxib. Conclusions: These data suggest that ibuprofen may confer an increased risk of thrombotic and CHF events relative to lumiracoxib among aspirin users at high cardiovascular risk. The study indicates that naproxen may be associated with lower risk relative to lumiracoxib among non-aspirin users. This study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study.