Strategies to optimize treatment with NSAIDs in patients at risk for gastrointestinal and cardiovascular adverse events

Abstract

Background: NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are among the most widely prescribed medications worldwide. However, NSAIDs have been associated with gastrointestinal (GI) toxicity. The cardiovascular (CV) toxicity associated with COX-2 inhibitors and some other NSAIDs further complicates the choice of therapy. Objective: The aim of this commentary was to appraise current NSAID treatment strategies and provide clinicians with guidance on the GI and CV risks of these strategies and choosing an appropriate treatment in individual patients. Methods: A literature search of PubMed was conducted (1989-August 2009) to gather relevant studies, meta-analyses, reviews, and treatment guidelines using the following terms, either alone or in combination: NSAID, gastrointestinal, cardiovascular, toxicity, gastroprotection, proton pump inhibitor, COX-2 inhibitor, aspirin, fixed-dose combination, and adherence. Results: Based on the data from the literature search, gastroprotective strategies (eg, proton pump inhibitors [PPIs]) are underused in patients at risk for NSAIDrelated GI complications, including in those patients most at risk. Risk factors for GI toxicity with NSAID use include high NSAID dose, a history of NSAID-associated GI adverse events or the presence of upper GI symptoms, advanced age, corticosteroid use, concurrent aspirin use, and certain comorbidities (eg, rheumatoid arthritis). Risk factors for CV toxicity with NSAID use include established CV disease or an estimated 10-year CV risk >20%. Findings from randomized controlled trials have suggested that, in patients with an increased risk for GI complications, the use of a nonselective NSAID with a PPI may be at least as effective as the use of a COX-2 selective inhibitor in preventing the recurrence of ulcer complications. In patients with a high GI risk and a moderate CV risk, the use of a COX-2 inhibitor with a PPI may be appropriate. Conclusions: The choice of NSAID should be tailored to the GI and CV risks in the patient. The risk profile can be affected by numerous factors, including NSAID dosing and concurrent aspirin use. Thus, individualized risk stratification should be the clinician's primary consideration when selecting treatment.