This review concluded that, in adults with hypertension, aliskiren was not better than angiotensin receptor blockers for controlling blood pressure. Data came from short-term trials which were not designed to show any effect on clinical outcomes. Overall, the authors' conclusions appear reasonable.

To determine whether aliskiren has any advantages over angiotensin receptor blockers in the treatment of hypertension.

PubMed (1966 to June 2010), EMBASE (1980 to June 2010) and Cochrane Central Registry of Controlled Trials (CENTRAL, 2010 Issue 2) were searched. Search terms were reported. No language restrictions were applied. Clinicaltrials.gov, Novartis Clinical Results Database and the reference lists of identified reviews and RCTs were checked.

Randomised controlled trials (RTCs) that compared aliskiren with angiotensin receptor blockers in patients with hypertension were eligible for inclusion. Participants could have other diseases (such as metabolic syndrome or diabetes).

The primary outcome of interest was the reduction from baseline to the end of treatment in mean clinic or 24-hour ambulatory systolic blood pressure or diastolic blood pressure. Other outcomes of interest were therapeutic blood pressure response (percentage of participants with mean diastolic blood pressure over 90mmHg and/or at least 10mmHg reduction from baseline), blood pressure control rate (the percentage of participants with mean diastolic blood pressure over 90mmHg and mean systolic blood pressure over 140mmHg), and adverse events (adverse events, severe adverse events or withdrawal due to adverse events).

In the included trials, men and women with mild to moderate hypertension were included. The mean age of participants ranged from 52 to 60 years. In most trials participants did not have co-morbidities, but some trials were on people with diabetes, obesity or metabolic syndrome. Dosages of aliskiren ranged from 75 to 300mg. The angiotensin receptor blockers used were irbesartan, losartan and valsartan (dosages ranged from 50 to 320mg).

Two reviewers independently assessed trials for inclusion. A third reviewer checked results.

The quality of trials was assessed using the Jadad scale (items on study design, intention-to-treat analysis, generation of randomisation sequence, completeness of follow-up, description or withdrawals). The maximum score was 5 points.

It appears that two reviewers assessed quality with disagreements resolved by discussion.

Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous data. Mean differences and 95% confidence intervals were calculated for continuous data. In one trial that compared different groups with different doses of aliskiren versus one group with angiotensin receptor blockers, only data for the highest dosage group were extracted. In a trial that compared different doses of aliskiren versus different doses of angiotensin receptor blockers, the authors extracted data as if each comparison was a separate trial with lower doses versus lower doses and higher doses versus higher doses. Where necessary authors were contacted for missing information.

Two reviewers independently extracted data. Disagreements were resolved by discussion.

Pooled relative risks and 95% confidence intervals and weighted mean differences (WMDs) and 95% confidence intervals were calculated using a random-effects and a fixed-effect method. Heterogeneity was assessed using Χ² and Ι².

Subgroup analyses were used to investigate the effect of different angiotensin receptor blockers.

Sensitivity analyses were used to investigate the effects of excluding trials of participants with coexisting metabolic syndrome, obesity or diabetes, trials that used combination therapies, and trials according to different dosages.

Publication bias was assessed using a funnel plot.

Ten trials (3,255 participants) were included in the review. Nine were of parallel design (3,229 participants) and one crossover (26 participants). Two trials compared aliskiren with losartan, three compared aliskiren with valsartan, and five compared aliskiren with irbesartan.

Eight trials scored 5 points for quality, one scored 4 points and one scored 3 points. All scored positive for randomisation, intention-to-treat analysis, completeness of follow-up, and description of withdrawals. Generation of random sequence was appropriate in eight trials, but unable to be assessed in two. Follow-up ranged from four to 12 weeks.

There was no difference between aliskiren and angiotensin receptor blockers in the reduction of mean clinic systolic or diastolic blood pressure (none trials), ambulatory systolic or diastolic blood pressure (four trials), therapeutic response rate (four trials) or blood pressure control rate (seven trials). Subgroup analyses showed no difference in mean clinic systolic or diastolic blood pressure compared with each angiotensin receptor blockers individually. Sensitivity analyses showed no difference in effect on clinic blood pressure for all analyses.

Compared with angiotensin receptor blockers (valsartan, irbesartan and losartan, combined or individually) aliskiren showed no difference in the incidence of adverse effects.

Funnel plot indicated an absence of publication bias.

In patients with hypertension, aliskiren was not superior to angiotensin receptor blockers in controlling blood pressure and did not differ in risks of adverse events..

The aims of this review and the inclusion criteria were clearly stated. The search included published and unpublished studies and was not limited by language. This was likely to have reduced the possibility of language or publication bias. The review methods were aimed at reducing the effect of reviewer error or bias.

Quality of the included trials was assessed and full details were listed. However, a scoring system was used which may not have accurately reflected the differences between trials. The methods of synthesis appeared generally appropriate, although it was not clear if appropriate methods were used to include data from a crossover trial. Heterogeneity was assessed. It was unclear whether the methods of dealing with trials with treatment groups of differing doses was the most appropriate. Information about the participants and concomitant therapies was limited; this could affect the generalisability or results.

The authors acknowledged that the trials were of short duration and not designed to show any effect on clinical outcomes. Overall, the authors' conclusions appear reasonable.

Practice: The authors did not state any implications for practice.

Research: The authors stated that longer term RCTs (at least 12 months and preferably five years or longer) were needed to assess the effects of aliskiren versus angiotensin receptor blockers on clinical outcomes in adults with hypertension. In particular, the trials should investigate how well aliskiren works in patients with an inadequate response to angiotensin receptor blockers.

National Natural Science Foundation of China; Doctoral Program of Higher Education of China research fund; Major Basic Research Development Program of China from the Ministry of Science and Technology.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.