VA Study: CV Risks Lower in Patients Taking NSAID, Misoprostol Combo

by U.S. Medicine

June 14, 2017

By Brenda L. Mooney

Mark Munger, PharmD, professor of pharmacotherapy at the University of Utah College of Pharmacy

SALT LAKE CITY — Use of nonsteroidal anti-inflammatory (NSAID) drugs has been linked to a higher risk of cardiovascular issues, but a new study offers a possible way to mitigate that factor.

A recent conference presentation suggested that patients who took misoprostol, used to prevent stomach ulcers, along with NSAIDs significantly lowered their risks of such events, as well as stroke and kidney failure, compared to those who took NSAIDS alone.

The research was presented at the American College of Cardiology’s 66th Annual Scientific Session in Washington this spring.1

The study team from the Salt Lake City VAMC and the University of Utah noted that NSAIDS are the most commonly used prescription and over-the-counter analgesic medications worldwide, but their use is limited by an increase in cardio-renal morbidity and mortality risk.

“Withdrawal of the balancing vasodilatory prostaglandins on vascular, thrombotic and renal physiological mechanisms by NSAIDs contributes to the cardio-cerebro-renal vascular event risk,” they pointed out, adding, “We hypothesized that restoration of prostanoids through the concomitant use of misoprostol with NSAIDs may reduce the adverse event risk.”

“Right now, clinicians have no direct treatment options to reduce the risk for these NSAID-induced cardio-renal complications, other than to advise against NSAID use, reduce the duration of use or recommend alternative pain management agents, so we set out to discover a treatment to reduce the risk of these effects,” explained lead author Mark Munger, PharmD, FCCP, professor of pharmacotherapy at the University of Utah College of Pharmacy. “Our data, from a large and well-characterized healthcare system, support a potentially safer NSAID alternative when NSAIDs are combined with misoprostol.”

The researchers conducted a historical cohort study using the VA database to compare new initiators of 11 different NSAIDs and/or misoprostol from 2005 through 2013, for a total of nearly 1.7 million subjects. The veterans were followed for five years, with a focus on development of cardiovascular, cerebrovascular or renal-vascular events. 

Patients taking NSAIDs and misoprostol together lowered by 44% their risk of having a heart attack, suffering cardiac arrest or having ventricular fibrillation, according to the study. At the same time, those taking both drugs also had a 25% lower risk of strokes or mini-strokes and a 34% lower risk of acute kidney failure compared to people taking NSAIDs alone.

The study involved two treatment groups, each containing 1,827 patients. Results indicate that NSAID plus misoprostol significantly reduced cardiovascular [hazard ratio (HR) of 0.56], cerebrovascular (HR of 0.75) and reno-vascular (0.66) vs. NSAID alone. All-cause mortality was not statistically different between groups, however, with an HR of 1.05.

“Taking misoprostol in conjunction with a NSAID significantly reduced the risk of NSAID-induced cardiovascular, cerebrovascular, and reno-vascular adverse events associated with taking NSAIDS alone,” study authors conclude. “This data from a large and well characterized healthcare system database supports a safer analgesic, an NSAID combined with misoprostol.”

“Hopefully we can reduce the incidence of NSAID-induced cardio-renal adverse effects, which could be especially important in an era in which pain management is in flux,” Munger added, pointing out that the growing problem of opioid abuse and addiction have made it even more critical to improve the safety profile of NSAIDs. 

  1. Munger M, Nelson SD, Teng CC, Bress A, Sauer B., Reduced Risk of NSAID Induced Adverse Events With Concomitant Use of Misoprostol, presented at ACC 17, 66TH Annual Scientific Session & Expo in Washington. March 17-19, 2017.

2 Comments

  • Shelly Berkowitz, MD says:

    In the article you state that (regarding taking NSAIDS plus misoprostol)”those taking both drugs also had a 25% lower risk of strokes or mini-strokes and a 34% lower risk of acute kidney failure compared to people taking NSAIDs alone.” Am I correct in my interpretation that the risks are still higher for these negative outcomes for individuals taking both NSAIDS and misoprostal than for those taking NEITHER of these medications/classes of medications? In addition, the traditional teaching is that NSAIDS interfere with the preventative effects of aspirin on CVR disease. I assume that adding misoprostol to NSAIDS will not prevent this interference.

  • Shelly Berkowitz, MD says:

    In the article you state that (regarding taking NSAIDS plus misoprostol)”those taking both drugs also had a 25% lower risk of strokes or mini-strokes and a 34% lower risk of acute kidney failure compared to people taking NSAIDs alone.” Am I correct in my interpretation that the risks are still higher for these negative outcomes for individuals taking both NSAIDS and misoprostal than for those taking NEITHER of these medications/classes of medications? In addition, the traditional teaching is that NSAIDS interfere with the preventative effects of aspirin on CVR disease. I assume that adding misoprostol to NSAIDS will not prevent this interference.


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