Background Renin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension is unknown. Objectives To evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension. Search methods The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. Selection criteria We included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension. Data collection and analysis Two review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. Main results We include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors for the outcomes: all-cause mortality: risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence; total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; very low-certainty evidence; adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants; moderate-certainty evidence; serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence; and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants; low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggested that RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants; and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants, to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect. Authors' conclusions For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ for all-cause mortality and myocardial infarction. We have low to moderate certainty that they do not differ for adverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty. More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessing morbidity and mortality outcomes, but also on blood pressure-lowering effect. Plain language summary How renin inhibitors (RIs) compare with angiotensin converting enzyme (ACE) inhibitors for treating hypertension Review question We determined how renin inhibitors (RIs) compared with angiotensin converting enzyme (ACE) inhibitors for treating hypertension. Background Hypertension is a worldwide public-health challenge associated with high levels of occurrence and risks of circulatory and kidney disease. RIs were introduced into clinical use for hypertension in 2007. ACE inhibitors are widely prescribed for hypertension. However, the comparative effectiveness and safety of RIs and ACE inhibitors is not known. Search date We searched for evidence up to August 2020. Study characteristics We included randomized, active-controlled, double-blinded studies (RCTs) for this review. We include 11 RCTs involving 13,627 participants, with an average age from 51 to 74 years. Length of follow-up ranged from four weeks to 36 months. Key results and certainty of evidence Low-certainty evidence showed no difference between RIs and ACE inhibitors for deaths from any cause, for heart attacks, for serious side effects or for leaving the study because of side effects. Low-certainty evidence suggested that RIs reduce blood pressure more than ACE inhibitors do, but this could have been due to bias in the design and conduct of the studies. More independent RCTs are needed to assess illnesses and deaths, and to see if the difference in blood pressure-lowering is real.
