McMurray, J.J.V., Pitt, B., Latini, R., Maggioni, A.P., Solomon, S.D., Keefe, D.L., Ford, J., Verma, A. and Lewsey, J. (2008) Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circulation: Heart Failure, 1(1), pp. 17-24. (doi: 10.1161/CIRCHEARTFAILURE.107.740704)
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Abstract
<b>Background</b>: Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure. <b>Methods and Results</b>: Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration >100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and β-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients’ mean age was 68 years, mean ejection fraction was 31%, and mean±SD systolic blood pressure was 129±17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo. <b>Conclusions</b>: Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Lewsey, Professor Jim and McMurray, Professor John |
Authors: | McMurray, J.J.V., Pitt, B., Latini, R., Maggioni, A.P., Solomon, S.D., Keefe, D.L., Ford, J., Verma, A., and Lewsey, J. |
Subjects: | R Medicine > R Medicine (General) |
College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Centre for Population and Health Sciences |
Journal Name: | Circulation: Heart Failure |
Publisher: | Lippincott Williams and Wilkins |
ISSN: | 1941-3289 |
ISSN (Online): | 1941-3297 |
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