Key messages
- The available evidence from short-term studies suggests there is probably little to no difference between renin inhibitors and angiotensin receptor blockers in terms of death rates, withdrawal due to unwanted effects, serious unwanted events, unwanted events, and blood pressure control for people with mild primary hypertension.
- Due to a lack of strong evidence from long-term studies, any potential differences between these two drugs for measures of heart and blood vessel health are unknown.
- Larger studies of longer duration are needed, which include a wider range of people and focus on measures of heart and blood vessel health.
What is hypertension?
Primary hypertension, also known as essential hypertension, is the kind of high blood pressure that starts on its own and is not caused by another health problem. Hypertension increases the risk of stroke, heart attack, and kidney disease. Hypertension guidelines recommend angiotensin receptor blockers (ARBs) as the first choice of treatment for people with hypertension, but do not make specific recommendations for renin inhibitors.
What did we want to find out?
We wanted to find out if renin inhibitors are better than ARBs for people with primary hypertension.
What did we do?
We searched for studies that examined renin inhibitors compared with ARBs in people with primary hypertension. We compared and summarised their results, and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We included 11 studies involving 6780 people, with an average age range of 52 to 59 years, who had mild primary hypertension and no heart problems. The studies lasted between four weeks and nine months. All the studies compared aliskiren, a type of renin inhibitor, with an ARB. The particular ARB used was losartan in four studies, valsartan in three studies, irbesartan in three studies, and telmisartan in one study.
The available evidence from short-term studies suggests little to no difference between renin inhibitors and ARBs in people with mild primary hypertension in terms of death rates, withdrawal due to unwanted effects, serious unwanted events, unwanted events, and blood pressure control. We found no data for end-stage renal disease.
What are the limitations of the evidence?
Our confidence is limited because of concerns about how some of the studies were conducted.
There are not enough studies to be certain about the death rate results.
We are less confident about the diastolic blood pressure results because the results of one study differed from the results of the others.
How up to date is this evidence?
We searched for evidence up to January 2024.
The available RCT evidence suggests little to no difference between renin inhibitors and ARBs in terms of mortality, SAE, WDAE, adverse events, and blood pressure in people with mild primary hypertension. The evidence was derived from short-term trials with a limited occurrence of morbidity outcomes, leaving any potential differences unknown. Larger RCTs of longer duration with a wider range of participants and a focus on cardiovascular outcomes are needed.
Renin inhibitors, which inhibit the first and rate-limiting step in the renin angiotensin system (RAS), are thought to be more effective than other RAS inhibitors in blocking the RAS. Previous meta-analyses have shown that renin inhibitors have a favourable tolerability profile in people with mild-to-moderate hypertension and a blood-pressure-lowering magnitude that is similar to that of angiotensin receptor blockers (ARBs).
ARBs inhibit the RAS by interfering with the binding of angiotensin II with its receptors. ARBs are widely prescribed and recommended as first-line therapy by some hypertension guidelines.
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 benefits and harms of renin inhibitors compared to ARBs in treating hypertension are unknown.
To evaluate the benefits and harms of renin inhibitors compared to angiotensin receptor blockers in people with primary hypertension.
On 26 January 2024, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials: Cochrane Hypertension’s Specialised Register, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform and the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) were also searched for ongoing trials. We contacted authors of relevant papers regarding further published and unpublished work and checked the bibliographies of included studies and relevant systematic reviews. The searches had no language restrictions.
We included randomised, double-blind, parallel-design clinical trials comparing renin inhibitors and ARBs for people with primary hypertension. Studies recruiting people with proven secondary hypertension were excluded.
Two review authors independently selected the included trials, evaluated the risks of bias using the RoB 1 tool, and entered the data for analysis. We reported dichotomous outcomes as a risk ratio (RR) with a 95% confidence interval (CI) and continuous variables as mean difference (MD) with a 95% CI. The primary outcomes were all-cause mortality, total cardiovascular events, end-stage renal disease (ESRD), withdrawal due to adverse effects (WDAE), serious adverse events (SAE), and adverse events. The secondary outcomes were fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, fatal heart failure or hospitalisation for heart failure, systolic and diastolic blood pressure (SBP and DBP), and heart rate. We used the GRADE approach to rate our confidence in the evidence.
We included 11 double-blind RCTs involving 6780 participants with mild primary hypertension and without cardiovascular complications (mean age range 52 to 59 years), with a mean follow-up ranging from four weeks to nine months. Risk of bias was low or unclear for most domains except for other bias, which was high risk for 10 of the 11 trials due to industry funding. All the studies compared aliskiren, the only marketed molecule in the class of renin inhibitors, with an ARB. The ARB comparator was losartan in four trials, valsartan in three trials, irbesartan in three trials, and telmisartan in one trial. There were very limited or no data on cardiovascular outcomes and ESRD.
There may be little to no difference between renin inhibitors and ARBs in all-cause mortality (RR 0.35, 95% CI 0.07 to 1.64; 3 studies, 1932 participants; low-certainty evidence). There is probably little to no difference between renin inhibitors and ARBs in WDAE (RR 0.71, 95% CI 0.49 to 1.02; 9 studies, 4634 participants; moderate-certainty evidence), SAE (RR 0.75, 95% CI 0.45 to 1.27; 6 studies, 3283 participants; moderate-certainty evidence), and adverse events (RR 0.98, 95% CI 0.90 to 1.06; 10 studies, 4722 participants; moderate-certainty evidence).
There is probably little to no difference between renin inhibitors and ARBs in lowering SBP (MD −0.25 mmHg, 95% CI −1.05 to 0.56; 10 studies, 4222 participants; moderate-certainty evidence) and there may be little to no difference in lowering DBP (MD 0.25 mmHg, 95% CI −0.14 to 0.64; 10 studies, 4222 participants; low-certainty evidence).