Abstract: 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

Plain-language summary: We found 12 studies, eight weeks in duration, that randomly assigned 7439 adult people with uncomplicated mild-to-moderate hypertension to aliskiren at doses ranging from 75 mg to 600 mg or placebo. All studies were funded by the manufacturer Novartis. Detailed information regarding adverse events, obtained from nine clinical study reports submitted to regulators, are included in this update. We concluded that aliskiren is better than placebo at lowering blood pressure and that the magnitude of this effect could be similar to other classes of drugs when 300 mg, which is the maximum recommended dose, is used. Aliskiren 300 mg reduced blood pressure by eight points in the upper number (called systolic blood pressure) and five points in the lower number (called diastolic blood pressure). Aliskiren had no effect on blood pressure changeability. Due to very limited information regarding change in heart rate and pulse pressure (difference between upper and lower number) it was not possible to analyze these outcomes. The studies were too short in duration to assess side effects. Aliskiren did not increase death, non-fatal serious adverse events or withdrawal due to side effects. The most common adverse events observed were headache, diarrhoea, dizziness and fatigue. Diarrhoea was considerably increased with aliskiren 600 mg as compared to placebo. The decrease in blood pressure at the recommended dose was rated as moderate-quality evidence and adverse event data was graded as low-quality evidence as included studies were assessed to have high likelihood of reporting and funding bias.