Blood pressure lowering efficacy of renin inhibitors for primary hypertension
Editorial Group: Cochrane Hypertension Group
Published Online: 8 OCT 2008
Assessed as up-to-date: 9 AUG 2011
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Musini VM, Fortin PM, Bassett K, Wright JM. Blood pressure lowering efficacy of renin inhibitors for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD007066. DOI: 10.1002/14651858.CD007066.pub2.
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 8 OCT 2008
Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. The renin-angiotensin-aldosterone system is an important target site for five antihypertensive drug classes: beta blockers, renin inhibitors, ACE inhibitors, angiotensin receptor blockers (ARBs) and aldosterone inhibitors. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors prevent the formation of both angiotensin I and angiotensin II . Renin inhibitors do not affect kinin metabolism and may produce fewer adverse effects than ACE inhibitors such as dry cough or angioedema.
To quantify the dose-related blood pressure lowering efficacy of renin inhibitors versus placebo in the treatment of primary hypertension.
We searched the following databases for randomised, double blind, placebo-controlled trials of renin inhibitors: Medline (1966-June 2011), EMBASE (1988-June 2011), Cochrane CENTRAL, the Hypertension Group Specialised Register and bibliographic citations from retrieved references. No language restrictions were applied.
Study design had to meet the following criteria: double-blinded, placebo-controlled; random allocation to a specific dose of renin inhibitor group and parallel placebo group; duration of follow-up of at least three weeks.
Data collection and analysis
Two reviewers independently extracted data and assessed trial quality using risk of bias tables. Disagreements were resolved by discussion or a third reviewer. Data synthesis and analyses were done using the Cochrane Review Manager software, RevMan 5.1. Data for continuous variables were combined using a weighted mean difference method and dichotomous variables were analysed using relative risk with 95% CI.
Eight trials met the inclusion criteria. Six trials (N=3694) in the original review and two additional trials comparing the renin inhibitor, aliskiren (N=3393), to placebo (N=1623 ) met the inclusion criteria for this updated review. Aliskiren was the only renin inhibitor studied in these studies. The meta-analysis shows that aliskiren has a dose-related systolic/diastolic blood pressure lowering effect as compared to placebo: aliskiren 75 mg -2.6/-2.1 mm Hg, aliskiren 150 mg -5.6/-2.9 mm Hg, aliskiren 300 mg -7.9/-4.8, aliskiren 600 mg -11.4/-6.6 mm Hg. Aliskiren 300 mg significantly lowered both SBP and DBP as compared to aliskiren150 mg (SBP:-2.97 (95% CI -3.50, -1.90) and DBP: -1.86 (95% CI -2.39, -1.33). Aliskiren has no effect on blood pressure variability. No data was available to assess the effect of aliskiren on heart rate and pulse pressure. This review found weak evidence that with short-term use, aliskiren does not increase withdrawals due to adverse effects as compared to placebo.
Aliskiren has a dose-related blood pressure lowering effect better than placebo. This effect is similar to that determined for ACE inhibitors and ARBs.
Plain language summary
Blood pressure lowering efficacy of aliskiren
Elevated blood pressure or hypertension can lead to heart attacks and stroke. A new class of drugs called renin inhibitors is indicated for the treatment of hypertension. Aliskiren is a member of this new class and is the only one studied (or approved) for this indication at this time. We asked whether aliskiren was better than placebo for reducing blood pressure in patients with hypertension, and whether this drug had increased side effects leading to withdrawals. We searched the scientific literature and found 8 randomised controlled trials comparing aliskiren to placebo. 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 the maximum recommended dose is used. The trials were too short to assess side effects.