The Long-term Risk for Myocardial Infarction or Stroke After Proton Pump Inhibitor Therapy (2008–2018)

Michael Nolde; Nayeon Ahn; Tobias Dreischulte; Ina-Maria Rückert-Eheberg; Florian Güntner; Alexander Günter; Roman Gerlach; Martin Tauscher; Ute Amann; Jakob Linseisen; Christa Meisinger; Sebastian-Edgar Baumeister


Aliment Pharmacol Ther. 2021;54(8):1033-1040. 

In This Article


We identified 1 143 948 initiators of PPI therapy and 36 229 initiators of H2RA therapy meeting the eligibility criteria in our data set of 6 097 740 individuals. 22 020 PPI initiators and 16 201 H2RA initiators received both medications during follow-up. Rates per 1000 person-years of MI and IS by exposure group are presented in Table 1. Covariate summaries of PPI and H2RA initiators, before and after weighting, are provided in Table 2 and Table S1. In the unweighted data, patients who started PPI therapy were older, more likely to suffer from GERD or Helicobacter pylori infection, and more likely to take non-steroidal anti-inflammatory drugs or anticoagulants. After weighting, both groups were well balanced on the confounders.

We found no evidence for an association of PPI vs H2RA initiation with MI or IS. The HR comparing PPI and H2RA initiation over 10 years was 0.96 (95% CI: 0.80–1.16) for MI and 0.98 (95% CI: 0.89–1.08) for IS. HRs for several follow-up periods are given in Table 3. Survival curves comparing the outcome-free survival among initiators of PPI therapy vs H2RA therapy were consistent with these findings (Figures 2 and 3). The HRs for comparing PPI initiators and non-initiators were 1.02 (95% CI: 0.94–1.10) for MI and 0.98 (95% CI: 0.94–1.02) for IS (Table 3). The lag time approach did not substantially change point estimates or precision (Table 3). The negative control analysis pointed to a small potential of unmeasured confounding influencing our observed HRs (Figure S1).

Figure 2.

As-started: PPI vs H2RA—baseline adjusted survival (Kaplan-Meier) curve for myocardial infarction

Figure 3.

As-started: PPI vs H2RA—baseline adjusted survival (Kaplan-Meier) curve for ischaemic stroke