Misoprostol Effects on Diclofenac‐Induced Cardiorenal Changes in Salt‐Sensitive Patients with Hypertension: The MEDIC Study

Munger, Mark A.; Gardner, Stephanie F.; Ateshkadi, Arasb; Rabetoy, Gary M.; Barri, Yoursi M.; Stoddard, Gregory J.; Cheung, Alfred K.

doi:10.1592/phco.28.7.834

Cited by 4 publications

(9 citation statements)

References 23 publications

(19 reference statements)

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“…Taking misoprostol in conjunction with a NSAID significantly reduced the cardiovascular, cerebrovascular, and renal adverse events associated with taking NSAIDs alone, especially in patients with complex comorbidities or high risk for complications. 18 These data from a large and well-characterized healthcare system support a potentially safer NSAID alternative when a NSAID is combined with misoprostol.…”

Section: All-cause Mortalitymentioning

confidence: 82%

“…16 The agent lowers mean arterial pressure, increases glomerular filtration rate and renal blood flow in diabetics with renal impairment and elderly salt-sensitive individuals in combination with a NSAID compared with NSAID monotherapy. 17,18 This population-based historical cohort of U.S. veterans study was designed to determine whether the combination of NSAID plus misoprostol exhibited a different cardio-renal risk profile versus NSAID monotherapy. Veteran patients were censored if there was no evidence of activity in the V.A.…”

Section: Introductionmentioning

confidence: 99%

“…It is indicated for NSAID‐induced gastric ulceration risk reduction in high‐risk patients, for example, the elderly and patients with concomitant debilitating disease 16 . The agent lowers mean arterial pressure, increases glomerular filtration rate and renal blood flow in diabetics with renal impairment and elderly salt‐sensitive individuals in combination with a NSAID compared with NSAID monotherapy 17,18 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: All-cause Mortalitymentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…The comparators in these studies were either associated with a similar neutral effect on mean SBP (naproxen 500 mg BID) [64] or a significant elevation in mean SBP of around 3.5 mmHg (rofecoxib 25 mg OD and ibuprofen 2031 mg mean daily dose) [64, 65]. The ambulatory BP effects of diclofenac have been investigated in relatively small populations (< 30 patients) [66, 67], and the data should therefore be treated cautiously. A consistent increase in mean SBP was seen in one crossover study of black and Hispanic patients when diclofenac (75 mg BID; 4.1 mmHg increase) was compared with celecoxib (200 mg OD; 0.6 mmHg increase) [66].…”

Section: Comparison Of Safety Profiles Of Celecoxib Etoricoxib Amentioning

confidence: 99%

“…A consistent increase in mean SBP was seen in one crossover study of black and Hispanic patients when diclofenac (75 mg BID; 4.1 mmHg increase) was compared with celecoxib (200 mg OD; 0.6 mmHg increase) [66]. In a second, small crossover study of patients (aged 55–73 years) with diagnosed hypertension, a significant BP-raising effect was seen with only 75 mg/day of diclofenac, and intriguingly this effect was partially reversed by the use of the prostaglandin E2 analog, misoprostol, over the course of the 3-week study [67].…”

Section: Comparison Of Safety Profiles Of Celecoxib Etoricoxib Amentioning

confidence: 99%

Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

Walker

2018

International Journal of Rheumatology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs—celecoxib, etoricoxib, and diclofenac—using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.

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

Mitsuboshi

Kotake

Takahashi

et al. 2023

Brit J Clinical Pharma

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AimsMisoprostol is a prostaglandin E1 analogue that is used to prevent nonsteroidal anti‐inflammatory drug (NSAID)‐induced gastrointestinal disorders. The aim of this systematic review and meta‐analysis was to evaluate whether use of misoprostol also decreases the risk of NSAID‐induced kidney injury.MethodsRandomized controlled trials that compared misoprostol vs. placebo in an adult patient population were selected. The primary outcome was kidney injury and the secondary outcome was severe adverse events. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsTwelve studies were eligible for inclusion. Although the rates of kidney injury and severe adverse events did not differ significantly between misoprostol and placebo, a posthoc subgroup analysis that excluded studies in which different NSAIDs were used in the misoprostol and placebo groups suggested that misoprostol may reduce the risk of NSAID‐induced kidney injury (risk difference −0.09, 95% confidence interval −0.15 to −0.03, P < .01, I2 = 87%; evidence of very low certainty).ConclusionThere is limited evidence that misoprostol reduces the risk of NSAID‐induced kidney injury. Misoprostol possibly contributes to reducing the risk of kidney injury associated with chronic NSAID use. The findings of this meta‐analysis suggest further high‐quality clinical trials are warranted.

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Misoprostol Effects on Diclofenac‐Induced Cardiorenal Changes in Salt‐Sensitive Patients with Hypertension: The MEDIC Study

Abstract: In senior salt-sensitive patients with hypertension, coadministration of misoprostol with diclofenac attenuated the blood pressure elevation and renal vasoconstrictive effects of diclofenac and was well tolerated.

Cited by 4 publications

References 23 publications

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

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

Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

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

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