Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial

• Published in: The Lancet (British edition) 2007-07, Vol.370 (9583), p.221-229
• Main Authors: Oparil, Suzanne, Prof, Yarows, Steven A, MD, Patel, Samir, MS, Fang, Hui, PhD, Zhang, Jack, MD, Satlin, Andrew, MD
• Format: Article
• Language: English
• Subjects: Abnormalities; Amides - adverse effects; Amides - pharmacology; Amides - therapeutic use; Antihypertensive Agents - adverse effects; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Blood Pressure - drug effects; Cardiology. Vascular system; Clinical trials; Double-Blind Method; Double-blind studies; Drug dosages; Drug therapy; Drug Therapy, Combination; Endpoint Determination; Evidence-based medicine; Female; Fumarates - adverse effects; Fumarates - pharmacology; Fumarates - therapeutic use; General aspects; Humans; Hypertension; Hypertension - drug therapy; Inhibitors; Internal Medicine; Laboratories; Male; Medical sciences; Metabolism; Middle Aged; Motivation; Patients; Pharmaceuticals; Plasma; Renin; Renin - antagonists & inhibitors; Renin - blood; Studies; Tetrazoles - adverse effects; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Titration; Valine - adverse effects; Valine - analogs & derivatives; Valine - pharmacology; Valine - therapeutic use; Valsartan
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(07)61124-6

Summary Background The aim of this study was to assess dual renin system intervention with the maximum recommended doses of aliskiren and valsartan, compared with each drug alone in patients with hypertension. Methods In this double-blind study, 1797 patients with hypertension (mean sitting diastolic blood pressure 95–109 mm Hg and 8-h daytime ambulatory diastolic blood pressure ≥90 mm Hg) were randomly assigned to receive once-daily aliskiren 150 mg (n=437), valsartan 160 mg (455), a combination of aliskiren 150 mg and valsartan 160 mg (446), or placebo (459) for 4 weeks, followed by forced titration to double the dose to the maximum recommended dose for another 4 weeks. The primary endpoint was change in mean sitting diastolic blood pressure from baseline to week 8 endpoint. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov with the number NCT00219180. Findings 196 (11%) patients discontinued study treatment before the end of the trial (63 in the placebo group, 53 in the aliskiren group, 43 in the valsartan group, and 37 in the aliskiren/valsartan group), mainly due to lack of therapeutic effect. At week 8 endpoint, the combination of aliskiren 300 mg and valsartan 320 mg lowered mean sitting diastolic blood pressure from baseline by 12·2 mm Hg, significantly more than either monotherapy (aliskiren 300 mg 9·0 mm Hg decrease, p