Aliskiren is a direct renin inhibitor and by inhibiting the enzyme renin it inhibits the renin-angiotensin system at its point of activation, blocking the conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin II.
The efficacy of aliskiren has been assessed in several randomised placebo-controlled studies in patients with essential hypertension (mean sitting diastolic blood pressure [msDBP] =95 and <110mmHg).
A study1 conducted in 672 patients assessed the efficacy of aliskiren versus placebo. Patients were randomised to receive once-daily, double-blind treatment with aliskiren, 150mg, 300mg or 600mg, or placebo for eight weeks. The primary objective of the study was to evaluate reductions in msDBP with aliskiren compared with placebo.
Aliskiren was significantly superior to placebo in lowering msDBP and msSBP. Comparisons revealed that all doses (150mg to 600mg) yielded significantly greater reductions in both msDBP and msSBP than placebo. After eight weeks’ treatment, aliskiren 150mg, 300mg and 600mg reduced msDBP by 10.3 ± 0.63, 11.1 ± 0.64, and 12.5 ± 0.64 mmHg, respectively, versus 4.9 ± 0.64 mmHg with placebo.
Another study2 conducted in 2,776 patients assessed the efficacy of aliskiren monotherapy and in combination with hydrochlorothiazide (HCTZ). Patients were randomised to receive double-blind treatment with placebo, aliskiren monotherapy (75mg, 150mg or 300mg), HCTZ monotherapy (6.25mg, 12.5mg or 25mg), or a combination of aliskiren and HCTZ (every dose combination except aliskiren/HCTZ 300/6.25mg) in a factorial design.
Aliskiren monotherapy was significantly superior to placebo in reducing msDBP. Aliskiren reduced msDBP in a dose-related manner. Least squares mean (LSM) reductions from baseline were 8.7 ± 0.59, 8.9 ± 0.59 and 10.3 ± 0.60mmHg at doses of 75mg, 150mg and 300mg respectively. HCTZ monotherapy reduced msDBP from baseline, although no linear dose relationship was observed (LSM reductions of 9.1±0.58, 10.1 ± 0.59 and 9.4 ± 0.61mmHg at doses of 6.25, 12.5 and 25mg respectively; all nominal P values were <0.01 versus placebo). The combination of aliskiren 300mg and HCTZ showed additional benefit versus the monotherapies.
A third study3 conducted in 1,797 patients assessed the efficacy of aliskiren monotherapy and aliskiren in combination with valsartan. Patients were randomly assigned in an equal ratio to once-daily oral administration of aliskiren 150mg, valsartan 160mg, the combination of aliskiren 150mg and valsartan 160mg or placebo for four weeks. This was followed by forced titration to double the dose to the maximum recommended dose for another four weeks.
At week eight (endpoint), treatment with the combination of aliskiren and valsartan reduced msDBP from baseline significantly more than aliskiren or valsartan monotherapy, or placebo. Monotherapy with aliskiren or valsartan provided significantly greater reductions in msDBP and msSBP compared to placebo at endpoint.
1. Oh B, Mitchell J, Herron J et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24 hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007: 49; 1,157–1,163.
2. Villamil A, Chrysant S, Calhoun D et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007: 25(1); 217–26.
3. Oparil S, Yarows S, Patel S et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007: 370; 221–9.
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