No reduction in cardiovascular risk with NSAIDs—including aspirin?

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) cause considerable morbidity in terms of dyspepsia, gastrointestinal haemorrhage, renal dysfunction, aggravation of hypertension, and precipitation of heart failure. 1 Weil J Colin-Jones D Langman M et al. Prophylactic use of aspirin and risk of peptic ulcer bleeding. BMJ. 1995; 310: 827-830 Crossref PubMed Scopus (549) Google Scholar , 2 Weil J Langman MJS Wainwright P et al. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal antiinflammatory drugs. Gut. 2000; 46: 27-31 Crossref PubMed Scopus (212) Google Scholar , 3 Cleland JGF John J Houghton T Does aspirin attenuate the effect of angiotensin-converting enzyme inhibitors in hypertension or heart failure?. Curr Opin Nephrol Hypertens. 2001; 10: 625-631 Crossref PubMed Scopus (34) Google Scholar , 4 Fored CM Ejerblad E Lindblad P et al. Acetaminophen, aspirin and chronic renal failure. N Engl J Med. 2001; 345: 1801-1808 Crossref PubMed Scopus (214) Google Scholar The gastrointestinal adverse effects are mediated largely through inhibition of cyclo-oxygenase-1 (COX-1). This enzyme is also needed for the production of thromboxane in platelets, and inhibition of thromboxane is purported to reduce the risk of cardiovascular events. Many NSAIDs, most notably naproxen, ibuprofen, and aspirin, inhibit platelet aggregation. 5 van Hecken A Schwartz JL Depre M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000; 40: 1109-1120 PubMed Google Scholar Cyclo-oxygenase-2 (COX-2) mediates not only the analgesic and antiinflammatory effects of NSAIDs but also the production of prostacyclin in the vascular wall, which may protect against cardiovascular events. COX-2 inhibitors are less likely than COX-1 inhibitors to induce adverse gastrointestinal effects. However, by inhibiting synthesis of prostacyclin in the vascular wall but not platelet thromboxane production, COX-2 inhibitors could theoretically increase the risk of cardiovascular events. The VIGOR (VIoxx Gastrointestinal Outcomes Research) study suggested that treatment with a COX-2 inhibitor, rofecoxib, was associated with a higher rate of non-fatal myocardial infarction than was a non-selective COX inhibitor, naproxen. 6 Bombardier C Laine L Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000; 343: 1520-1528 Crossref PubMed Scopus (3696) Google Scholar This observation may have reflected a chance finding, a reduction in vascular events with the nonselective agent, or an increase in vascular events with the COX-2 inhibitor, or it may just have been an “illusion”. Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort studyAbsence of a protective effect of naproxen or other NANSAIDs on risk of coronary heart disease suggests that these drugs should not be used for cardioprotection. Full-Text PDF