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Nolde, Michael; Ahn, Nayeon; Dreischulte, Tobias; Krause, Evamaria; Guentner, Florian; Guenter, Alexander; Gerlach, Roman; Tauscher, Martin; Amann, Ute; Linseisen, Jakob; Meisinger, Christa; Baumeister, Sebastian-Edgar and Rueckert-Eheberg, Ina-Maria (2022): Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: A systematic review and meta-analysis of observational studies. In: European Journal of Internal Medicine, Vol. 106: pp. 80-89

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Background and Aims: Observational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality. Methods: The databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding.Results: We included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovas-cular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96;1.15) before and 0.99 (0.93;1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11;1.44) before and 1.06 (0.96;1.16) after adjusting for publication bias and observational study design bias. Conclusion: It is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor.

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