Document Detail


The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio.
MedLine Citation:
PMID:  17606839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's. Our primary hypothesis was that in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. METHODS AND RESULTS: Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K+, elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of > or = 20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg (P<0.005). Amiloride 40 mg was as effective as the other diuretics. Biochemical indices of natriuresis showed bendroflumethiazide to be less effective than either spironolactone or amiloride; plasma renin rose 4-fold on spironolactone but only 2-fold on bendroflumethiazide (P=0.003). CONCLUSIONS: In hypertensive patients with a low plasma renin but normal K+, bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone. Because this result differs from that expected in primary hyperaldosteronism, our finding argues against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism. However, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na+ retention of low-renin hypertension.
Authors:
Susan J Hood; Kevin P Taylor; Michael J Ashby; Morris J Brown
Related Documents :
1337459 - Reversal of cardiovascular structural changes when treating essential hypertension. the...
17490489 - Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflum...
6999899 - Normotensive primary aldosteronism.
6116609 - Antihypertensive effect of e-643, a new alpha-adrenergic blocking agent.
16156509 - Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration ...
2743599 - Increased sympathetic nerve activity at home in young subjects with hypertension.
10919419 - Cricoid pressure: which hand?
11554219 - Hemodynamic evaluation of the female sexual arousal response in an animal model.
2210809 - Sequential spectral analysis of 24-hour blood pressure and pulse interval in humans.
Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2007-07-02
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-08-07     Revised Date:  2008-03-05    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  268-75     Citation Subset:  AIM; IM    
Affiliation:
Clinical Pharmacology Unit, Department of Medicine, University of Cambridge, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Aldosterone / blood*
Amiloride / therapeutic use*
Bendroflumethiazide / therapeutic use
Cross-Over Studies
Double-Blind Method
Female
Humans
Hypertension / blood,  drug therapy*
Losartan / therapeutic use*
Male
Middle Aged
Renin / blood*
Single-Blind Method
Sodium Chloride Symporter Inhibitors / therapeutic use*
Spironolactone / therapeutic use*
Chemical
Reg. No./Substance:
0/Sodium Chloride Symporter Inhibitors; 114798-26-4/Losartan; 2609-46-3/Amiloride; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 73-48-3/Bendroflumethiazide; EC 3.4.23.15/Renin
Comments/Corrections
Comment In:
Circulation. 2008 Feb 5;117(5):e151; author reply e152   [PMID:  18250276 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Symptoms of tobacco dependence after brief intermittent use: the Development and Assessment of Nicot...
Next Document:  Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditio...