In the Journals

Proton pump inhibitors may increase MI risk

Adults in the U.S. exposed to proton pump inhibitors were at increased risk for developing MI in a recent data-mining study.

The researchers evaluated data collected from more than 16 million clinical documents on 2.9 million patients to assess the possible link between proton pump inhibitor (PPI) use and CV risk.

The primary data source was the STRIDE database at Stanford University (1.8 million patients), and a Web-based electronic health record system (Practice Fusion Inc.) was the secondary source (1.1 million patients). STRIDE included data from 1994 to 2011, and the Web-based database included data from 2007 to 2012.

The data were evaluated for PPI use after an indication for gastroesophageal reflux disease (GERD), followed by incidence of MI. Evaluated PPIs included dexlansoprazole (Dexilant, Takeda Pharmaceuticals), esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole.

A link between PPI use and MI was observed in both data sets. The STRIDE database included 70,477 adult patients with GERD, 22,411 of whom had MI and 45.9% of whom used one or more PPI. Among these patients, researchers calculated an adjusted OR for MI of 1.16 (95% CI, 1.09-1.24). This association varied slightly according to the specific PPI used (range, 1.08-1.34). The observed link was consistent across age groups, and persisted after exclusion of patients receiving clopidogrel (adjusted OR = 1.14; 95% CI, 1.06-1.24). The researchers noted that patients treated with H2 blockers, an alternative GERD therapy, did not have increased risk for MI (adjusted OR = 0.93; 95% CI, 0.86-1.02).

Analysis of the second data set, which included 227,438 patients with GERD, yielded similar results to the STRIDE database (adjusted OR = 1.19; 95% CI, 1.09-1.3).

The researchers also evaluated data collected from 1,503 patients enrolled in the GenePAD prospective cohort study and calculated a significantly increased risk for CV-related mortality among PPI users after adjustment for CV comorbidities (HR = 2; 95% CI, 1.07-3.78). Similarly to the STRIDE analysis, H2 blockers were not associated with increased risk in this population (HR = 1; 95% CI, 0.14-7.26).

They added that, if pharmacovigilance algorithms such as the one employed in this analysis had been available, the increased CV risk associated with lansoprazole use could have been identified as early as 2000.

Although the researchers wrote that these results are subject to confounding — and that PPI use may simply indicate a sicker patient population —they concluded that their findings are “hypothesis-generating” and warrant additional investigation.

“Our report raises concerns that these drugs — which are available over the counter and are among the most commonly prescribed drugs in the world — may not be as safe as we previously assumed,” researcher Nicholas J. Leeper, MD, of the divisions of cardiovascular medicine and vascular surgery at Stanford University, said in a press release.

– by Adam Taliercio

Disclosure: The study was partially funded by Apixio Inc. Several researchers report being inventors and/or holding patents for methods owned by Stanford University that enable the use of clinical text for data-mining. Two researchers are founders of Altitute Pharma Inc., a biotechnology company developing PPI-based products for airway diseases. One researcher is an employee of Practice Fusion Inc.

Adults in the U.S. exposed to proton pump inhibitors were at increased risk for developing MI in a recent data-mining study.

The researchers evaluated data collected from more than 16 million clinical documents on 2.9 million patients to assess the possible link between proton pump inhibitor (PPI) use and CV risk.

The primary data source was the STRIDE database at Stanford University (1.8 million patients), and a Web-based electronic health record system (Practice Fusion Inc.) was the secondary source (1.1 million patients). STRIDE included data from 1994 to 2011, and the Web-based database included data from 2007 to 2012.

The data were evaluated for PPI use after an indication for gastroesophageal reflux disease (GERD), followed by incidence of MI. Evaluated PPIs included dexlansoprazole (Dexilant, Takeda Pharmaceuticals), esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole.

A link between PPI use and MI was observed in both data sets. The STRIDE database included 70,477 adult patients with GERD, 22,411 of whom had MI and 45.9% of whom used one or more PPI. Among these patients, researchers calculated an adjusted OR for MI of 1.16 (95% CI, 1.09-1.24). This association varied slightly according to the specific PPI used (range, 1.08-1.34). The observed link was consistent across age groups, and persisted after exclusion of patients receiving clopidogrel (adjusted OR = 1.14; 95% CI, 1.06-1.24). The researchers noted that patients treated with H2 blockers, an alternative GERD therapy, did not have increased risk for MI (adjusted OR = 0.93; 95% CI, 0.86-1.02).

Analysis of the second data set, which included 227,438 patients with GERD, yielded similar results to the STRIDE database (adjusted OR = 1.19; 95% CI, 1.09-1.3).

The researchers also evaluated data collected from 1,503 patients enrolled in the GenePAD prospective cohort study and calculated a significantly increased risk for CV-related mortality among PPI users after adjustment for CV comorbidities (HR = 2; 95% CI, 1.07-3.78). Similarly to the STRIDE analysis, H2 blockers were not associated with increased risk in this population (HR = 1; 95% CI, 0.14-7.26).

They added that, if pharmacovigilance algorithms such as the one employed in this analysis had been available, the increased CV risk associated with lansoprazole use could have been identified as early as 2000.

Although the researchers wrote that these results are subject to confounding — and that PPI use may simply indicate a sicker patient population —they concluded that their findings are “hypothesis-generating” and warrant additional investigation.

“Our report raises concerns that these drugs — which are available over the counter and are among the most commonly prescribed drugs in the world — may not be as safe as we previously assumed,” researcher Nicholas J. Leeper, MD, of the divisions of cardiovascular medicine and vascular surgery at Stanford University, said in a press release.

– by Adam Taliercio

Disclosure: The study was partially funded by Apixio Inc. Several researchers report being inventors and/or holding patents for methods owned by Stanford University that enable the use of clinical text for data-mining. Two researchers are founders of Altitute Pharma Inc., a biotechnology company developing PPI-based products for airway diseases. One researcher is an employee of Practice Fusion Inc.