Spotlight on PPIs

Myocardial infarction risk appeared no greater with proton-pump inhibitors (PPIs) than with histamine H2 receptor antagonists in one recent study, while another study looked at the effect of a trainee-led program on inappropriate PPI infusions in hospitalized patients.


A recent study found no greater risk of myocardial infarction (MI) with proton-pump inhibitors (PPIs) compared to histamine H2 receptor antagonists (H2 blockers), while another study found that a trainee-led program successfully reduced inappropriate PPI infusions in the hospital.

As part of the first study, researchers used national administrative claims from commercial insurance plans and Medicare Supplement Insurance plans from 2001 to 2014. They followed more than 5 million new users of PPIs and H2 blockers from their first prescription until MI (defined using hospital diagnosis codes), medication discontinuation, plan disenrollment, or Dec. 31, 2014. They excluded patients with an MI diagnosis in the year prior to the first prescription.

PPI initiators outnumbered H2 blocker initiators in both insurance cohorts (commercial insurance: n=3,675,120 for PPIs and n=829,441 for H2 blockers; Medicare Supplement: n=894,821 for PPIs and n=192,607 for H2 blockers). The primary outcome was risk of MI after initiation of either medication, weighted by several covariates (e.g., demographic characteristics, concomitant medications, comorbidities). Results were published online on Nov. 6 by Gastroenterology.

Median follow-up was 60 days for patients with commercial insurance and 96 days for patients with Medicare Supplement plans. Overall, the 12-month weighted risk of MI was low (about 2 cases per 1,000 patients with commercial plans and about 8 per 1,000 patients with Medicare Supplement plans).

In both insurance populations, researchers found no significant difference in 12-month MI risk between patients who started PPIs and those who started H2 blockers. “Thus, physicians and patients should not avoid starting a PPI because of concerns related to MI risk,” the study authors concluded. They noted that limitations of the analysis include short-term follow-up, factors not captured in the claims data (e.g., smoking status), and the over-the-counter availability of the medications.

The second study looked at PPI use in a more specific population of patients with upper gastrointestinal bleeding. As part of a trainee-led intervention to reduce the inappropriate use of PPI infusions in this population and lower costs, the electronic health record (EHR) was changed to prompt physicians to select an appropriate indication for PPI infusion orders, such as before endoscopy. Pharmacists tracked monthly usage of PPI infusions, and faculty leaders educated residents, hospitalists, and emergency medicine clinicians on appropriate use. Results of the intervention were published online as a research letter on Nov. 1 by JAMA Internal Medicine.

Researchers compared data on PPI infusion usage, indication, and endoscopic findings from the postintervention period (July 2015 to April 2016) to the preceding year (July 2014 to June 2015) among historical control patients admitted for upper GI bleeding. Over this time, inappropriate use of PPI infusion significantly decreased from a mean of 50% (95% CI, 45.1% to 54.7%) to a mean of 15% (95% CI, 10.0% to 18.5%), a 35% reduction (95% CI, −44.6% to −27.1%; P<0.001).

A single PPI infusion was estimated to cost $378 per day, compared to an estimated cost of $100.87 to administer PPIs twice daily, yielding a cost savings of $277 per patient per day. The researchers estimated a resultant pharmacy cost savings of at least $121,000 over nine months.

The researchers did not observe the significant decrease in inappropriate use among surgical services that had access to the EHR changes but no other components of the intervention, which used a Culture, Oversight, Systems Change, Training framework. “Access to the systems change alone did not result in significant changes, highlighting the importance of including all aspects of the framework in the intervention,” the study authors wrote. They noted that the study was limited by a lack of randomization and blinding, as well as a lack of information on the number of patients who were discharged with inappropriate PPI therapy.