Summing the risk of NSAID therapy

Abstract

Reports concluding that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the likelihood of cardiovascular adverse events have led patients and clinicians to reduce use. It is intriguing to recollect that the cardiotoxicity of NSAIDs (both cyclo-oxygenase-2 [COX-2] selective inhibitors and non-selective dual inhibitors have been implicated) would not have been revealed if not for the push to market novel drugs developed to reduce the well-documented gastrointestinal complications of this widely used class. While weighing risks and benefits of interventions is an essential component of clinical decisionmaking, it has become increasingly complex to decide in whom the use of any NSAID—with or without a gastroprotective agent, and with or without concomitant aspirin—is appropriate. In view of the multiplicity, and in many cases rarity, of adverse events, it is unlikely that a single mega-trial will adequately address the numerous safety and effectiveness issues. In the meantime, careful synthesis of the literature—not complete reliance on single studies that address one outcome—is required to inform decisionmaking. This stepwise approach is crucial, because appropriate selection of an NSAID should be driven by assessment of an individual's cardiovascular and gastrointestinal risk, or both, rather than by a drug's reported rate of adverse events in heterogeneous populations (table). 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar TableClinicians guide to anti-infl ammatory therapy in 2007 No or low NSAID gastrointestinal risk NSAID gastrointestinal risk No cardiovascular risk (without aspirin) Nonselective NSAID (cost consideration) COX-2 selective inhibitor or non-selective NSAID+proton-pump inhibitor COX-2 selective inhibitor+proton-pump inhibitor for those with prior gastrointestinal bleeding Cardiovascular risk (with aspirin) Naproxen * Non-selective or selective (low-dose) inhibitor without established aspirin interaction if naproxen is ineffective.2 Proton-pump inhibitor irrespective of NSAID Addition of proton-pump inhibitor if gastrointestinal risk of aspirin/NSAID combination warrants gastroprotection Naproxen if CV risk outweighs gastrointestinal risk COX-2 selective inhibitor+proton-pump inhibitor for those with previous gastrointestinal bleeding Misoprostol at full dose (200 μg four times a day) may be substituted for proton-pump inhibitor. Adapted from 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar . * Non-selective or selective (low-dose) inhibitor without established aspirin interaction if naproxen is ineffective. 2 Grosser T Fries S Fitzgerald GA Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Cllin Invest. 2006; 116: 4-15 Crossref PubMed Scopus (822) Google Scholar Open table in a new tab Misoprostol at full dose (200 μg four times a day) may be substituted for proton-pump inhibitor. Adapted from 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar . Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trialPatients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding. Full-Text PDF