1. Pich, Jacqueline PhD, BSc, BNurs


Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. For more information, see


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Are renin inhibitors effective and safe in reducing primary hypertension?



This is a systematic review of 12 studies comparing renin inhibitors with placebo.



Hypertension, defined as a systolic blood pressure (SBP)/diastolic blood pressure (DBP) greater than 140/90 mmHg in people not taking antihypertensive medication, is a major risk factor for stroke, coronary heart disease, heart failure, kidney disease, and peripheral vascular disease. The risk factors for hypertension include older age and lifestyle factors such as poor diet (particularly high salt intake), obesity, excessive alcohol consumption, and insufficient physical activity. Therefore, hypertension management includes lifestyle changes, although these are often supplemented by medications, specifically antihypertensive drugs. The renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and fluid balance. It has been speculated that, by inhibiting production of renin and preventing the production of angiotensin I and II, renin inhibitors might provide a more effective means of blocking the action of the RAAS than existing classes of antihypertensive drugs.



The purpose of this review was to determine the blood pressure-lowering efficacy of renin inhibitors compared with placebo. It involved the drug aliskiren-the only renin inhibitor approved for the treatment of hypertension-and included both published and unpublished studies of double-blind, randomized controlled trials (RCTs) that compared different doses of aliskiren with placebo.


The primary outcome was a change from baseline SBP and DBP over a minimum of three to 12 weeks. Secondary outcomes included serious adverse events, such as mortality; nonfatal serious adverse events; and adverse events such as a dry cough, diarrhea, and angioedema.


Twelve studies were included in the review, involving a total of 7,439 adults with mild-to-moderate hypertension who were given aliskiren at doses ranging from 75 mg to 600 mg, or placebo. Aliskiren at all doses lowered SBP and DBP more effectively than placebo. There were dose-dependent decreases in blood pressure with the 75-mg, 150-mg, and 300-mg aliskiren doses. Although the effect on blood pressure of the 600-mg dose was no different from that of the 300-mg dose, there was a statistically significant relationship between the 600-mg aliskiren dose and the adverse effect of diarrhea.



Aliskiren was superior to placebo in lowering mean SBP and DBP. Adverse events included dry cough, headache, dizziness, fatigue, and diarrhea and were associated with increased aliskiren doses. The authors note, however, that the results of this study should be viewed with caution. They discovered discrepant reporting or nonreporting of important safety outcomes that "limit our ability to evaluate the safety and efficacy of aliskiren as compared to placebo."



Because the goal of antihypertensive therapy is to reduce morbidity and mortality, more RCTs of longer duration are needed to study the long-term effects of renin inhibitors compared with other antihypertensive drug classes. Moreover, the reporting inconsistencies and possible bias in this review should serve as a reminder that RCTs must provide data on all studied outcomes and all negative studies must be published so that future reviews can provide an accurate summary of the best available evidence.




Musini VM, et al. Blood pressure lowering efficacy of renin inhibitors for primary hypertension. Cochrane Database Syst Rev 2017;4:CD007066.