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

Ben Schöttker,Liesa Katharina Hoppe,Hermann Brenner,Dana Clarissa Muhlack,Wolfgang Koenig

doi:10.1007/s10557-019-06894-w

Ben Schöttker, Liesa Katharina Hoppe + Show 3 more

Open Access

https://doi.org/10.1007/s10557-019-06894-w

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Abstract

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

Highlights

Over-the-counter (OTC) drugs are medications that can be bought without a prescription, which often happens without a physician’s advice or knowledge
The prevalence of diseases and cardiac events was higher in the ESTHER study, while elevated urinary albumin levels (≥ 20 mg/L) were more prevalent in the UK Biobank indicating a higher proportion of participants with potential kidney damage in this cohort
An explanation may be that we mainly focused on non-potassium-sparing diuretics users, who are rather prone to hypokalemia than to hyperkalemia

Summary

Introduction

Over-the-counter (OTC) drugs are medications that can be bought without a prescription, which often happens without a physician’s advice or knowledge. Older individuals use OTC drugs frequently [1, 2]. In the USA, concurrent use of prescription and OTC drugs is present in 46% of community-residing individuals aged 57 to 85 years [3]. Laxatives could interact with nonpotassium-sparing diuretics, which are prescribed to one in five of the elderly [6], because both drug classes can decrease serum potassium levels [7, 8]. Due to the narrow range of Cardiovasc Drugs Ther (2019) 33:567–579 physiological serum potassium levels (3.5 to 5.0 mmol/L), potassium depletion may result in hypokalemia [9, 10]. Since adequate levels are of high importance for heart rhythm and function, hypokalemia can cause arrhythmias and even cardiac death [11,12,13]

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