Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case
Celine S L Chui1,2,3, Ka Shing Cheung4,5, Jeremy P Brown6
1School of Nursing, University of Hong Kong, Hong Kong SAR, China.
Background:
Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator.
Methods:
We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates.
Results:
A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively.
Conclusions:
We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding.
Insights
Proton pump inhibitors (PPIs) do not increase myocardial infarction (MI) risk when compared to H2 receptor antagonists (H2RAs) in a self-controlled case series study. The apparent increased MI risk with PPIs is likely due to protopathic bias, not a true association.
Area of Science:
- Cardiovascular epidemiology
- Pharmacovigilance
- Gastroenterology
Background:
- Previous studies on cardiovascular risks of acid-suppressing drugs are limited by protopathic bias and confounding.
- Investigating the short-term risk of myocardial infarction (MI) associated with proton pump inhibitors (PPIs) requires robust methodologies.
Purpose of the Study:
- To evaluate the association between short-term myocardial infarction (MI) risk and proton pump inhibitors (PPIs).
- To address protopathic bias and confounding using a self-controlled case series (SCCS) with an active comparator.
Main Methods:
- A self-controlled case series (SCCS) design was employed using a Hong Kong population database (2003-2014).
- Adults with myocardial infarction (MI) exposed to proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) were included.
- Comparator-adjusted estimates were derived using simple ratio and effect modifier approaches within the SCCS framework.
Main Results:
- Initial analyses showed a higher risk of MI within 14 days of starting PPIs (IRR: 2.30) or H2RAs (IRR: 2.46) compared to baseline.
- Novel SCCS analyses using H2RAs as active comparators revealed no significant difference in MI risk for PPIs (simple ratio: 0.93; effect modifier: 0.83).
Conclusions:
- Proton pump inhibitors (PPIs) do not appear to increase the short-term risk of myocardial infarction (MI) when compared to H2 receptor antagonists (H2RAs).
- The observed elevated MI risk with PPIs in prior studies is likely attributable to protopathic bias.
- Active comparator SCCS designs show promise for mitigating protopathic bias and confounding in drug safety research.
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