Blood pressure lowering efficacy of renin inhibitors for primary hypertension

  • Review
  • Intervention


  • Vijaya M Musini,

    Corresponding author
    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
    • Vijaya M Musini, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Science Mall, Vancouver, BC, V6T 1Z3, Canada.

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  • Patricia M Fortin,

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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  • Ken Bassett,

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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  • James M Wright

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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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.

Search methods

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.

Selection criteria

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.

Main results

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.

Authors' conclusions

Aliskiren has a dose-related blood pressure lowering effect better than placebo. This effect is similar to that determined for ACE inhibitors and ARBs.








レニン阻害薬に関するランダム化二重盲検プラセボ比較試験について、次のデータベースを検索した。Medline(1966年~2011年6月)、EMBASE(1988年~2011年6月)、Cochrane CENTRAL、Hypertension Group Specialised Registerおよび抽出した参考文献の文献目録引用。 言語に制約は設けなかった。




2名のレビューアが別々にデータを抽出し、バイアスリスクの表を用いて試験の質を評価した。不一致については、議論または第3レビューアが解決した。データの統合と解析は、Cochrane Review ManagerソフトウェアRevMan 5.1を用いて実施した。連続変数のデータは、重み付き平均差法を用いて統合し、二値変数は、相対リスクおよび95%CIを用いて解析した。


8件の試験が本レビューの選択基準に合致した。初回レビューで選択された6件の試験(3,694例)、およびレニン阻害薬、アリスキレン(3,393例)とプラセボ(1,623例)が比較され、その後追加された2件の試験が、今回の更新レビューの選択基準に合致した。アリスキレンは、これらの研究において検討された唯一のレニン阻害薬であった。メタアナリシスでは、アリスキレンはプラセボと比較して、用量依存的に収縮期/拡張期血圧を低下させる効果があることが示され、アリスキレン75mgで-2.6/-2.1mmHg、アリスキレン150mgで-5.6/-2.9mmHg、アリスキレン300mgで-7.9/-4.8、アリスキレン600mgで-11.4/-6.6mmHgであった。アリスキレン300mgは、アリスキレン150mgと比較して、収縮期および拡張期血圧を有意に低下させた[収縮期血圧:-2.97(95%CI -3.50~-1.90)および拡張期血圧:-1.86(95%CI -2.39~-1.33)]。アリスキレンは血圧変動性に影響しない。アリスキレンの心拍数および脈圧に対する効果を評価するためのデータは得られなかった。本レビューでは、短期使用の場合、アリスキレンはプラセボと比較して、有害作用による中止例が増加しないことを示す弱いエビデンスが認められた。




Translated by: MINDS

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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.