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Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death.

ABSTRACT: No reduction in either coronary mortality or sudden cardiac death (SCD) has been demonstrated in overviews of randomized trials of treatment of hypertension with diuretics.An overview was conducted of coronary mortality and SCD in randomized controlled antihypertensive trials in which an epithelial sodium channel (ENaC) inhibitor/ hydrochlorthiazide (HCTZ) combination was used. Secondarily, an analogous overview in which thiazide diuretic was used alone was performed. Randomized trials that used an ENaC inhibitor/ HCTZ combination (or, alternatively, thiazide diuretic alone) were identified from previous meta-analyses, searches of PubMed, search of the Cochrane Clinical Trials database, and review of publications that addressed the consequences of treating hypertension. Trials in which participants were randomized to either an ENaC inhibitor combined with a thiazide diuretic (or to a thiazide diuretic alone) or to control treatment for at least one year and in which coronary mortality was reported were included. Numbers of events in individual trials were abstracted independently by 2 authors.Significant reductions in both coronary mortality and SCD were observed in the overview of trials in which elderly patients received an ENaC inhibitor/ HCTZ combination. The odds ratio (OR) for coronary mortality was 0.59 (95% confidence interval [CI] 0.44, 0.78) and for SCD was 0.60 (95% CI 0.38, 0.94). In contrast, an overview of the trials using thiazide diuretics alone showed no significant reductions of either coronary mortality (OR 0.94; 95% CI 0.81, 1.09) or SCD (OR 1.27; 95% CI 0.93, 1.75).Use of an ENaC inhibitor combined with HCTZ for treatment of hypertension in the elderly results in favorable effects on coronary mortality and SCD.

SUBMITTER: Hebert PR

PROVIDER: S-EPMC2633478 | biostudies-literature | 2008 Sep-Oct

REPOSITORIES: biostudies-literature

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Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death.

Hebert Patricia R PR Coffey Christopher S CS Byrne Daniel W DW Scott Theresa A TA Fagard Robert H RH Rottman Jeffrey N JN Murray Katherine T KT Oates John A JA

Journal of the American Society of Hypertension : JASH 20080901 5

<h4>Background</h4>No reduction in either coronary mortality or sudden cardiac death (SCD) has been demonstrated in overviews of randomized trials of treatment of hypertension with diuretics.<h4>Methods</h4>An overview was conducted of coronary mortality and SCD in randomized controlled antihypertensive trials in which an epithelial sodium channel (ENaC) inhibitor/ hydrochlorthiazide (HCTZ) combination was used. Secondarily, an analogous overview in which thiazide diuretic was used alone was per ...[more]

PMID: 19727429

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Project description:BackgroundSudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS.MethodsWe did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system.FindingsFour (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057).InterpretationRare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths.FundingUK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.

Dataset Information

Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death.

Publications

Treatment of elderly hypertensive patients with epithelial sodium channel inhibitors combined with a thiazide diuretic reduces coronary mortality and sudden cardiac death.

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