Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials

Abstract Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified popu...

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Autores principales:	Man Yang, Qiangsheng He, Fang Gao, Krish Nirantharakumar, Tonny Veenith, Xiwen Qin, Amy T. Page, Martin C. S. Wong, Junjie Huang, Zi Chong Kuo, Bin Xia, Changhua Zhang, Yulong He, Wenbo Meng, Jinqiu Yuan, Yihang Pan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Proton pump inhibitor, Stroke, Cohort, Meta-analysis, Randomized control trial Medicine R
Acceso en línea:	https://doaj.org/article/44a52398f61e4a96a59955dad6a895f9
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spelling	oai:doaj.org-article:44a52398f61e4a96a59955dad6a895f92021-12-05T12:11:14ZRegular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials10.1186/s12916-021-02180-51741-7015https://doaj.org/article/44a52398f61e4a96a59955dad6a895f92021-12-01T00:00:00Zhttps://doi.org/10.1186/s12916-021-02180-5https://doaj.org/toc/1741-7015Abstract Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.Man YangQiangsheng HeFang GaoKrish NirantharakumarTonny VeenithXiwen QinAmy T. PageMartin C. S. WongJunjie HuangZi Chong KuoBin XiaChanghua ZhangYulong HeWenbo MengJinqiu YuanYihang PanBMCarticleProton pump inhibitor, Stroke, Cohort, Meta-analysis, Randomized control trialMedicineRENBMC Medicine, Vol 19, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Proton pump inhibitor, Stroke, Cohort, Meta-analysis, Randomized control trial Medicine R
spellingShingle	Proton pump inhibitor, Stroke, Cohort, Meta-analysis, Randomized control trial Medicine R Man Yang Qiangsheng He Fang Gao Krish Nirantharakumar Tonny Veenith Xiwen Qin Amy T. Page Martin C. S. Wong Junjie Huang Zi Chong Kuo Bin Xia Changhua Zhang Yulong He Wenbo Meng Jinqiu Yuan Yihang Pan Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
description	Abstract Background Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.
format	article
author	Man Yang Qiangsheng He Fang Gao Krish Nirantharakumar Tonny Veenith Xiwen Qin Amy T. Page Martin C. S. Wong Junjie Huang Zi Chong Kuo Bin Xia Changhua Zhang Yulong He Wenbo Meng Jinqiu Yuan Yihang Pan
author_facet	Man Yang Qiangsheng He Fang Gao Krish Nirantharakumar Tonny Veenith Xiwen Qin Amy T. Page Martin C. S. Wong Junjie Huang Zi Chong Kuo Bin Xia Changhua Zhang Yulong He Wenbo Meng Jinqiu Yuan Yihang Pan
author_sort	Man Yang
title	Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
title_short	Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
title_full	Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
title_fullStr	Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
title_full_unstemmed	Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
title_sort	regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
publisher	BMC
publishDate	2021
url	https://doaj.org/article/44a52398f61e4a96a59955dad6a895f9
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Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials

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