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Cardiovasc Drugs Ther. 2019 Oct;33(5):567-579. doi: 10.1007/s10557-019-06894-w.

The Associations of Diuretics and Laxatives Use with Cardiovascular Mortality. An Individual Patient-Data Meta-analysis of Two Large Cohort Studies.

Author information

1
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
2
Network Aging Research, University of Heidelberg, Bergheimer Straße 20, 69115, Heidelberg, Germany.
3
Deutsches Herzzentrum München, Technische Universität München, Lazarettstraße 36, 80636, Munich, Germany.
4
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Pettenkoferstraße 8a & 9, 80336, Munich, Germany.
5
Institute of Epidemiology and Medical Biometry, University of Ulm, Helmholtzstraße 22, 89081, Ulm, Germany.
6
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. b.schoettker@dkfz-heidelberg.de.
7
Network Aging Research, University of Heidelberg, Bergheimer Straße 20, 69115, Heidelberg, Germany. b.schoettker@dkfz-heidelberg.de.

Abstract

PURPOSE:

To investigate the associations of diuretics overall, non-potassium-sparing diuretics in specific, and laxative use with cardiovascular mortality (CVM) in subjects with antihypertensive treatment.

METHODS:

Analyses included 4253 participants, aged 50 to 75 years, from the German ESTHER cohort and 105,359 participants, aged 50 to 69 years, from the UK Biobank. Cox proportional hazard regression models were applied in both studies, and then results were pooled using random-effects model meta-analyses.

RESULTS:

During 14 and 7 years of follow-up, 476 and 1616 CVM cases were observed in the ESTHER study and the UK Biobank, respectively. Compared to non-users, a 1.6-fold (hazard ratio [95% confidence interval] 1.57 [1.29; 1.90]), a 1.4-fold (1.39 [1.26; 1.53]), and no statistically significantly increased (1.13 [0.94; 1.36]) CVM were observed in users of diuretics overall, non-potassium-sparing diuretics in specific, and laxatives, respectively. Concurrent use of non-potassium-sparing diuretics and laxatives was associated with a 2-fold increased CVM (2.05 [1.55; 2.71]) when compared to users of neither diuretics nor laxatives. However, a test for interaction slightly missed statistical significance (p = 0.075).

CONCLUSIONS:

These consistent results from two large cohort studies imply that more research is needed on the safety of diuretics in routine care. Although not statistically significant in this study, a drug-drug interaction of non-potassium-sparing diuretics and laxatives appears plausible. Physicians and pharmacists are advised to clarify additional laxative use in users of non-potassium-sparing diuretics and inform about the risk of concurrent use. Moreover, closer potassium monitoring intervals (e.g., every 3 months) might be indicated in concurrent users to prevent fatal cardiovascular events.

KEYWORDS:

Cardiovascular mortality; Cohort study; Diuretics; Epidemiology; Laxatives

PMID:
31375970
DOI:
10.1007/s10557-019-06894-w

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