Nineteen trials (17 published and two unpublished) were included in the meta-analyses (44,639 patients). Mean follow-up ranged from 2.5 to 6.1 years (where reported). Data from 11 of the included studies were from subgroup analyses (four planned and seven post hoc). All published trials were rated as fair quality; no information on study quality was provided for unpublished trials. Drop-out was not reported in six trials, was greater than 20% in nine trials and less than 20% in two. Funnel plot and Egger’s test showed no evidence of publication bias.
Renin-angiotensin system blockade was associated with a statistically significant reduction in risk of myocardial infarction compared with controls (RR 0.82, 0.72 to 0.94; Ι²=49%; 19 data points from 17 trials) and reduced risk of a major cardiovascular event approaching statistical significance (RR 0.92, 95% CI 0.86 to 1.00; Ι²=53%; 21 data points from 19 trials). No statistically significant reductions were found for stroke, cardiovascular death and all-cause mortality.
There was no evidence for an association between blood pressure and cardiovascular outcomes (15 trials).
Subgroup analyses that found studies published before 2003 (but not after 2003) had a statistically significant reduced risk of myocardial infarction for renin-angiotensin system blockade (RR 0.72, 95% CI 0.57 to 0.89). ACE-inhibitors were associated with a statistically significant reduction in risk for myocardial infarction (RR 0.77, 95% CI 0.64 to 0.92) but this was not found for ARBs. No other variables examined in subgroup analyses appeared to impact on heterogeneity.