Starting a prescription proton pump inhibitor (PPI) conferred no short-term increase in risk for myocardial infarction in a large retrospective insurance claims study.

Over a median follow-up of 2-3 months, estimated weighted risks of first-ever MI were low and similar regardless of whether patients started PPIs or histamine 2 receptor antagonists (H2RAs), reported Suzanne N. Landi of the University of North Carolina at Chapel Hill, and her associates. “Contrary to prior literature, our analyses do not indicate increased risk of MI in PPI initiators compared to histamine 2 -receptor antagonist initiators,” they wrote in the March issue of Gastroenterology .

Epidemiologic studies have produced mixed findings on PPI use and MI risk. Animal models and ex vivo studies of human tissue indicate that PPIs might harm coronary vessels by increasing plasma levels of asymmetrical dimethylarginine, which counteracts the vasoprotective activity of endothelial nitrous oxide synthase, the investigators noted. To further assess PPIs and risk of MI while minimizing potential confounding, they studied new users of either prescription PPIs or an active comparator, prescription H2RAs. The dataset included administrative claims for more than 5 million patients with no MI history who were enrolled in commercial insurance plans or Medicare Supplemental Insurance plans. The study data spanned from 2001 to 2014, and patients were followed from their initial antacid prescription until they either developed a first-ever MI, stopped their medication, or left their insurance plan. Median follow-up times were 60 days in patients with commercial insurance and 96 days in patients with Medicare Supplemental Insurance, which employers provide for individuals who are at least 65 years old.

After controlling for numerous measurable clinical and demographic confounders, the estimated 12-month risk of MI was about 2 cases per 1,000 commercially insured patients and about 8 cases per 1,000 Medicare Supplemental Insurance enrollees. The estimated 12-month risk of MI did not significantly differ between users of PPIs and H 2 RAs, regardless of whether they were enrolled in commercial insurance plans (weighted risk difference per 1,000 users, –0.08; 95% confidence interval, –0.51 to 0.36) or Medicare Supplemental Insurance (weighted risk difference per 1,000 users, –0.45; 95% CI, –1.53 to 0.58) plans.

Each antacid class also conferred a similar estimated risk of MI at 36 months, with weighted risk differences of 0.44 (95% CI, –0.90 to 1.63) per 1,000 commercial plan enrollees and –0.33 (95% CI, –4.40 to 3.46) per 1,000 Medicare Supplemental Insurance plan enrollees, the researchers reported. Weighted estimated risk ratios also were similar between drug classes, ranging from 0.87 (95% CI, 0.76 to 0.99) at 3 months among Medicare Supplemental Insurance enrollees to 1.08 (95% CI, 0.87 to 1.35) at 36 months among commercial insurance plan members.

“Previous studies have examined the risk of MI in PPI users and compared directly to nonusers, which may have resulted in stronger confounding by indication and other risk factors, such as BMI [body mass index] and baseline cardiovascular disease , ” the investigators wrote. “Physicians and patients should not avoid starting a PPI because of concerns related to MI risk.”The researchers received no grant support for this study. Ms. Landi disclosed a student fellowship from UCB Biosciences.

SOURCE: Source: Landi SN et al. Gastroenterology. 2017 Nov 6. doi: 10.1053/j.gastro.2017.10.042 .


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