Prevention of non‐steroidal anti‐inflammatory drug gastrointestinal complications – review and recommendations based on risk assessment

Summary The incidence of non‐steroidal anti‐inflammatory drug‐related ulcer complications remains high despite the availability of potent anti‐ulcer drugs and selective cyclo‐oxygenase‐2 inhibitors. Non‐steroidal anti‐inflammatory drug‐related ulcer complications can be minimized by prospective assessment of patients’ baseline risk, rational choice and use of non‐steroidal anti‐inflammatory drugs, and selective use of co‐therapy strategies with gastroprotectives. Current recommendations regarding strategies using anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors for prevention of clinical non‐steroidal anti‐inflammatory drug upper gastrointestinal events are largely derived from studies using surrogates such as endoscopic ulcers, erosions, and symptoms in low‐ to average‐risk patients. Conclusions based on surrogate and potentially manipulatable end‐points are increasingly suspect with regard to applicability to clinical situations. This article reviews the risks associated with non‐steroidal anti‐inflammatory drugs including aspirin and includes the effect of the patients’ baseline risk, and the confounding effects of Helicobacter pylori infection. In addition, uncertainties regarding the clinical efficacy of anti‐ulcer drugs and cyclo‐oxygenase‐2 inhibitors against non‐steroidal anti‐inflammatory drug‐related ulcer complications are put into perspective. We propose management strategies based on the risk category: low risk (absence of risk factors) (least ulcerogenic non‐steroidal anti‐inflammatory drug at lowest effective dose), moderate risk (one to two risk factors) (as above, plus an antisecretory agent or misoprostol or a cyclo‐oxygenase‐2 inhibitor), high risk (multiple risk factors or patients using concomitant low‐dose aspirin, steroids, or anticoagulants) (cyclo‐oxygenase‐2 inhibitor alone with steroids, plus misoprostol with warfarin, or plus a proton pump inhibitors or misoprostol with aspirin), and very high risk (history of ulcer complications) (avoid all non‐steroidal anti‐inflammatory drugs, if possible or a cyclo‐oxygenase‐2 plus a proton pump inhibitors and/or misoprostol). The presence of H. pylori infection increases the risk of upper gastrointestinal complications in non‐steroidal anti‐inflammatory drug users by two‐ to fourfold suggesting that all patients requiring regular non‐steroidal anti‐inflammatory drug therapy be tested for H. pylori .