Efficacy and safety of aliskiren and amlodipine combination therapy in patients with hypertension: a randomized, double-blind, multifactorial study

Abstract

Most patients with hypertension need more than one drug to achieve blood pressure (BP) control. This randomized, double-blind, multifactorial study evaluated whether combinations of aliskiren and amlodipine provided superior BP reductions to component monotherapies in patients with hypertension (mean sitting diastolic BP (msDBP) 95-<110 mm Hg). Overall, 1688 patients were randomized to once-daily monotherapy with aliskiren 150 or 300 mg or amlodipine 5 or 10 mg, combination therapy with one of four corresponding aliskiren/amlodipine doses, or placebo for 8 weeks. At week 8 end point, aliskiren/amlodipine combinations provided significant msDBP reductions from baseline of 14.0-16.5 mm Hg, compared with reductions of 8.0 and 10.2 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 11.0 and 13.8 mm Hg for amlodipine 5 and 10 mg, respectively (P<0.05). Aliskiren/amlodipine combinations provided reductions in mean sitting systolic BP 20.6-23.9 mm Hg, compared with decreases of 10.7 and 15.4 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 15.8 and 21.0 mm Hg for amlodipine 5 (P< or =0.001) and 10 mg (P=NS), respectively. Aliskiren/amlodipine combination therapy provides greater BP lowering than either agent alone, hence offering an effective treatment option for patients with hypertension.

Differing Effects of Aliskiren/Amlodipine Combination and High‐Dose Amlodipine Monotherapy on Ambulatory Blood Pressure and Target Organ Protection

“…Similar to a previous report, 17 the aliskiren add-on to amlodipine therapy provided mean 24-hour, daytime, and nighttime BP reduction on ABPM, as did h-dAML. However, to the best of our knowledge, there is no report on the effect of aliskiren on early-morning BP and morning BP surge on ABPM.…”

“…There is substantial evidence that the prognostic power of ambulatory BP monitoring (ABPM) for cardiovascular and renal diseases is higher than that of clinic BP monitoring . In a relatively large patient population, the combination of aliskiren and amlodipine, which is commonly used as a first choice of hypertensive treatment, was reported to produce BP reduction on ABPM that was similar to that of high‐dose amlodipine monotherapy . However, to our knowledge, there is no published information about the relationship between the change in BP level on ABPM and asymptomatic organ damage.…”

Additivity of nebivolol/valsartan single‐pill combinations versus other single‐pill combinations for hypertension

“…BP data for four nebivolol/valsartan SPCs (nebivolol 5 mg/valsartan 80 mg, 5/160 mg, 10/160 mg, and 10/320 mg) were obtained from a previously reported phase 3, randomized, double‐blind, placebo‐controlled trial (NAC‐MD‐01; NCT01508026) . Five Food and Drug Administration–approved, non–β‐blocker/RAAS inhibitor SPCs were identified as comparators: aliskiren/hydrochlorothiazide (150/12.5 mg, 150/25 mg, 300/12.5 mg, 300/25 mg); aliskiren/amlodipine (150/5 mg, 150/10 mg, 300/5 mg, 300/10 mg); aliskiren/valsartan (150/160 mg, 300/320 mg); valsartan/amlodipine (160/5 mg, 160/10 mg, 320/5 mg, 320/10 mg); and telmisartan/amlodipine (40/5 mg, 40/10 mg, 80/5 mg, 80/10 mg) . BP data for the comparators were collected from pivotal, randomized, double‐blind, placebo‐controlled efficacy and safety trials available on the Drugs@FDA website…”

“…All trials occurred over 8 weeks and included a single‐blind run‐in period ranging from 2 to 6 weeks. At least one active treatment was uptitrated in all trials: amlodipine doses were doubled after 1 to 2 weeks hydrochlorothiazide doses were doubled after 1 week, and doses of all active treatments were doubled in the aliskiren/valsartan and nebivolol/valsartan trials after 4 weeks …”

“…The majority of trials also excluded participants with hypertensive encephalopathy/stroke, valvular heart disease, myocardial infarction, and history of transient ischemic attack . Details of the inclusion and exclusion criteria for all trials have been previously published …”