Reduced risk of NSAID‐Induced adverse events with concomitant use of misoprostol (MICRO study)

Abstract

Background Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events. Objectives The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol. Methods A population‐based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent‐to‐treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score‐weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR). Results The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow‐up was 35.2 ± 14.5 months. There were 439 total cardio‐renal events (5.62/1000 patient‐months) in the NSAID group and 419 patients (5.01/1000 patient‐months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78–1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34–0.93; p < 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60–0.94, p < 0.0001) and for renal (HR: 0.67; 95% CI: 0.49–0.89, p < 0.0001) events. All‐cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88–1.25, p = 0.61). Conclusion Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID‐induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol.

Association between misoprostol and nonsteroidal anti‐inflammatory drug‐induced kidney injury: A systematic review and meta‐analysis

“…38 Furthermore, in veteran patients in the USA who received NSAIDs, the risks of cardiovascular events, cerebrovascular events and kidney injuries were reduced by 10-40% when coadministered with misoprostol. 9 These findings are in line with those of the present study. It is worth noting that kidney injury was assessed in 3 studies based on an increase in the serum creatinine level and in 1 study based on mild renal insufficiency.…”

“…One double‐blind crossover trial found that misoprostol prevented diclofenac‐induced increases in mean arterial pressure and decreases in glomerular filtration rate, suggesting that misoprostol may prevent NSAID‐induced elevation in blood pressure and renal vasoconstriction 38 . Furthermore, in veteran patients in the USA who received NSAIDs, the risks of cardiovascular events, cerebrovascular events and kidney injuries were reduced by 10–40% when coadministered with misoprostol 9 . These findings are in line with those of the present study.…”

“…6,7 Misoprostol, a prostaglandin E1 analogue, prevents NSAIDinduced gastrointestinal disorders 5,8 and is also expected to prevent NSAID-induced kidney injury. A large cohort study suggested that use of misoprostol reduced the risk of NSAID-induced kidney injury by 11%, 9 and a small randomized controlled trial (RCT) suggested that misoprostol prevents the indomethacininduced decrease in glomerular filtration rate. 10 However, other studies have reported that misoprostol did not prevent NSAIDinduced kidney injury.…”

Comparison of misoprostol and manual vacuum aspiration in treating first-trimester incomplete miscarriage: a systematic review and meta-analysis of randomized controlled trials

“…Therefore, intake of ibuprofen (600 mg) 1 hour before the use of misoprostol could be helpful in reducing both fever and abdominal pain [28] . Previous reports also indicated that ibuprofen (600 mg) could be taken every eight hours in severe cases to avoid high temperature and abdominal pain [29][30][31] . In addition, since misoprostol was a prostaglandin E1 analogue, it might have bene ts in relieving gastric or duodenal ulcers [32,33] .…”