Does the ratio of serum aldosterone to plasma renin activity predict the efficacy of diuretics in hypertension? Results of RENALDO

Parthasarathy, H. K., Alhashmi, K., McMahon, A. D. , Struthers, A. D., McInnes, G. T., Ford, I. , Connell, J. M. and MacDonald, T. M. (2010) Does the ratio of serum aldosterone to plasma renin activity predict the efficacy of diuretics in hypertension? Results of RENALDO. Journal of Hypertension, 28(1), pp. 170-177. (doi:10.1097/HJH.0b013e328332b79b)

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Publisher's URL: http://dx.doi.org/10.1097/HJH.0b013e328332b79b

Abstract

<b>Objectives:</b> We hypothesized that the aldosterone: renin ratio (ARR) predicts the antihypertensive response to mineralocorticoid receptor antagonist, spironolactone (SPIRO), when compared with bendroflumethiazide (BFZ).<p></p> <b>Methods:</b> We conducted a randomized, crossover, trial on hypertensive patients with either high ARR (HARR defined as >750 and plasma aldosterone >250 pmol/l) or low ARR (LARR defined as <300 and plasma renin activity <10 ng/ml per h). Each group took SPIRO 50 mg once daily for 12 weeks and BFZ 2.5 mg once daily for 12 weeks in random order separated by 2-week washout. Patients with mean 24-h systolic ambulatory blood pressure (SABP) at least 140 mmHg were included. Primary endpoint was difference in SABP between SPIRO and BFZ in patients with HARR compared with those with LARR.<p></p> <b>Results:</b> One hundred and eleven patients (60 HARR and 51 LARR) completed the study. SABP at 12 weeks in the HARR group was 129.4 mmHg on SPIRO and 134.4 mmHg on BFZ [difference −5.01; 95% confidence interval (CI) −7.51, −2.52; P < 0.0002]. In the LARR group, SABP was 129.7 mmHg on SPIRO and 133.1 mmHg on BFZ [difference −3.43 (95% CI −6.18, −0.68) P < 0.01]. Difference between groups (HARR vs. LARR) was −1.58 mmHg (95% CI 5.25, −2.08; not significant, P = 0.394). In a secondary analysis of the overall study population of 111 patients, SABP reduction with SPIRO 50 mg was superior to BFZ 2.5 mg [SPIRO −14.8 mmHg, BFZ −10.5 mmHg, difference −4.29 mmHg (95% CI −6.12, −2.46)].<p></p> Results were similar for secondary endpoints. Plasma renin activity or aldosterone did not predict blood pressure response to SPIRO. Results were independent of concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use.<p></p> <b>Conclusion:</b> The ARR did not predict the blood pressure response to SPIRO. SPIRO 50 mg was significantly more effective than BFZ 2.5 mg in lowering SABP irrespective of baseline ARR, plasma renin activity or aldosterone.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ford, Professor Ian and McInnes, Professor Gordon and McMahon, Dr Alex and Connell, Professor John
Authors: Parthasarathy, H. K., Alhashmi, K., McMahon, A. D., Struthers, A. D., McInnes, G. T., Ford, I., Connell, J. M., and MacDonald, T. M.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins, Ltd.
ISSN:0263-6352
ISSN (Online):1473-5598

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences