Recent evidence suggests that both cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs, with the possible exception of naproxen, increase cardiovascular (CV) hazard. Clinicians should assess not only patients' GI risk but also their CV risk before prescribing these drugs. Patients with low CV risk can be managed according to their GI risk—low-risk patients (without risk factors) receive nonselective NSAIDs, medium risk patients (1–2 risk factors) receive COX-2 inhibitors or nonselective NSAIDs plus a proton pump inhibitor (PPI) or misoprostol, whereas high-risk patients (multiple risk factors, previous ulcer complications, or concomitant anticoagulants) receive a COX-2 inhibitor plus a PPI or misoprostol. Among patients with high CV risk (e.g., prior cardiothrombotic events) who require NSAIDs, naproxen is preferred. These patients should receive a prophylactic PPI or misoprostol because the risk of ulcer bleeding is substantially increased with concomitant use of naproxen and low-dose aspirin. Substitution of clopidogrel for aspirin is not recommended in patients at risk for upper GI bleeding who require antiplatelet therapy. Patients with high GI and high CV risk should avoid NSAIDs and COX-2 inhibitors. If antiinflammatory analgesics are required, the choice of therapy depends on the relative importance of GI and CV risks of individual patients. Combination of naproxen, low-dose aspirin, and a PPI or misoprostol is recommended if CV risk is the major concern (e.g., recent myocardial infarction). In contrast, combination of low-dose COX-2 inhibitor, low-dose aspirin, and a PPI or misoprostol is preferred if GI risk outweighs CV risk (e.g., recent ulcer bleeding and stable CV disease).
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
Reprint requests and correspondence: Francis K.L. Chan, M.D., F.A.C.G., Professor of Medicine, Chief of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong, China.
The manuscript was partly presented at the David Y. Graham Lecture of the 70th annual scientific meeting of the American College of Gastroenterology in November 2, 2005.
Received March 20, 2007; accepted August 2, 2007.
CONFLICT OF INTEREST Dr. Francis K.L. Chan has received an independent research grant and a consulting fee from Pfizer and paid lecture fees from TAP Pharmaceuticals and AstraZeneca.