CV, General Safety of Long-Term PPI Use Examined – The Cardiology Advisor

In the United States, proton pump inhibitors (PPIs) are one of the most widely used classes of drugs and are the most effective drugs for treating Gastroesophageal reflux disease (GERD). Given their high usage, it is crucial to ensure their safety.

Researchers discovered that long-term adverse events (AE)were similar in patients receiving pantoprazole compared with those receivingplacebo, according to a study published inGastroenterology.

In this 3 X 2 partial factorial, multicenter, double-blind, randomized, placebo-controlled trial, researchers analyzed the outcomes of participants with stable cardiovascular (CV) disease and peripheral artery disease (N=17,598) who were not already taking a PPI at baseline. Study participants were randomly assigned to groups receiving pantoprazole 40 mg daily (n=8791) or matching placebo daily (n=8807), between March 2013 and May 2016. They had also been randomly assigned to receive rivaroxaban 2.5 mg daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg once daily alone to compare the primary outcomes of CV death, stroke, or myocardial infarction (MI).

There was no significant difference in the primary efficacyoutcome when comparing combinations of rivaroxaban and aspirin for thecomposite outcome of MI, stroke, or CV death (hazard ratio [HR] 1.04; 95%confidence interval [CI], 0.93-1.15) with pantoprazole compared with placebo.No significant difference in the secondary CV efficacy outcomes of therivaroxaban/aspirin trial and no difference between pantoprazole and placebowas found separately for MI (HR 0.94; 95% CI, 0.79-1.12), stroke (HR 1.16; 95%CI, 0.94-1.44), or acute limb ischemia (HR 1.13; 95% CI, 0.73-1.75).

The rates of hospitalization (HR 1.04; 95% CI, 0.99-1.09)and all-cause mortality (HR 1.03; 95% CI, 0.92-1.15) were similar between thepantoprazole and placebo groups, as well as the non-CV events of interest,including pneumonia, fracture, new diagnosis of diabetes mellitus, chronickidney disease, dementia, chronic obstructive lung disease, and gastricatrophy. However, enteric infections were more frequent in the pantoprazolegroup compared with the placebo group (odds ratio [OR] 1.33; 95% CI,1.01-1.75).

This trial was potentially limited by underestimation of theincidence of gastric atrophy because the researchers relied on participantsbeing referred for endoscopy and having a gastric biopsy. While the proportionof gastric atrophy cases was similar between the 2 groups, the number ofparticipants was small and may have biased the results toward the null. Theassociations of proton pump inhibitor therapy with B-12 deficiency and gastriccancer are not supported by these randomized data, although a small effectcannot be excluded. The low numbers of apparent excess ofC difficile-associated diarrhea need tobe interpreted cautiously. There is possible misclassification regarding thisand other enteric infections because these AEs were obtained mainly by patientinterview every 6 months.

In conclusion, the researchers suggested that proton pumpinhibitors are not associated with any long-term harm other than possibleenteric infections for up to a median of 3 years. Moreover, the benefits arelikely to outweigh the risks forthese medications when clinicallyindicated.

Reference

Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin.Gastroenterology.2019;157(3):682-691.e2.

This article originally appeared on Gastroenterology Advisor

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CV, General Safety of Long-Term PPI Use Examined - The Cardiology Advisor