Four RCTs (n=17,337) were included in the review.
The quality of the included studies was high (interquartile range: 3, 5).
Combination ACE inhibitor plus ARB therapy versus control treatment that included ACE inhibitors was associated with a significant increase in medication discontinuation due to adverse effects in chronic HF patients (15.0% versus 11.0%; RR 1.38, 95% CI: 1.22, 1.55; 3 trials) and also in patients with AMI and symptomatic LVD (9.0% versus 7.6%; RR 1.17, 95% CI: 1.03, 1.34; 1 trial). There was no evidence of statistical heterogeneity.
Combination ARB plus ACE inhibitor therapy versus control treatment was associated with significant increases in the risk of symptomatic hypotension in chronic HF (2.4% versus 1.5%; RR 1.50, 95% CI: 1.09, 2.07; 3 trials) and also in patients with AMI and symptomatic LVD (18.1% versus 11.9%; RR 1.48, 95% CI: 1.33, 3.18; 1 trial).
Worsening renal function occurred more often with combination ARB plus ACE inhibitor therapy versus control treatment in patients with chronic HF (3.3% versus 1.5%; RR 2.17, 95% CI: 1.59, 2.97) and in patients with AMI with symptomatic LVD (4.8% versus 3.0%; RR 1.61, 95% CI: 1.31, 1.98).
There was a significant increase in the risk of hyperkalemia in both patient groups (RR 4.87, 95% CI: 2.39, 9.94; 3 trials; RR 1.48, 95% CI: 1.33, 3.18; 1 trial).