A large systematic review has found no evidence that angiotensin receptor blockers (ARBs) increase the risk of MI. Compared with patients on other active treatment or placebo, those on ARBs also had a lower risk of stroke, heart failure and diabetes.

The researchers analysed a total of 37 randomised controlled trials (39 comparator arms) with 147,020 patients. The comparator arms included 17 arms that compared ARBs with placebo and 22 arms that compared ARBs with active treatment. In all, 73,298 (49.8%) were taking ARBs and 73,722 (50.2%) were controls (placebo/active treatment). The average follow-up was 3.3 years (range 1-6.5 years), with a total follow-up across all trials of 485,166 patient-years.

Twelve of the 37 trials were considered at high risk of bias but the remainder as low risk. The results showed that ARBs were not associated with an increase in the risk of MI, RR 0.99 (95% CI: 0.92-1.07, p=0.85). The results were similar when ARBs were compared with either active treatment or placebo. Nor were they associated with an increased risk of death, cardiovascular death, or angina pectoris when compared with controls.

ARBs, not unexpectedly, were also associated with a significant reduction in the risk of stroke, RR 0.90 (95% CI: 0.84-0.98); heart failure, RR 0.87 (95% CI: 0.81-0.93) and new onset diabetes, RR 0.85 (95% CI: 0.78-0.93). However, despite lower blood pressure with ARBs when compared with placebo, there was no detectable beneficial effect on cardiovascular mortality.

This is a large and comprehensive analysis and has produced firm evidence to refute the hypothesis that ARBs increase the risk of MI. The authors comment that they were able to rule out as low as a 0.3% absolute increase. Furthermore, compared with controls, ARBs reduced the risk of stroke, heart failure, and new onset diabetes.

The concern that ARBs may increase the risk of MI has mainly arisen from under-powered observations and secondary endpoint analysis of several ARB trials but such observations can cause clinicians some concern. I am not certain to what degree this has influenced the prescribing of this class of drugs but this recent meta-analysis should now lay this concern to rest.

From a practical perspective, I would still stick with ACEIs as the first-line renin angiotensin system drug for the indications discussed above but when ACEIs are genuinely not tolerated, and cardioprotection is not the sole aim of treatment, then ARBs would appear to be a safe and effective alternative.

Dr Peter Savill

• Bangalore S, Kumar S, Wetterslev J, Messerli FH. Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147,020 patients from randomised trials. BMJ 2011;342:d2234