Dose of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcomes in Heart Failure: A Meta-Analysis

Background The association between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) doses on outcomes in patients with heart failure (HF) with reduced ejection fraction is uncertain. The objective of this study was to investigate the effect of dose of ACEI and ARBs on outcomes and drug discontinuation in patients with HF with reduced ejection fraction. Methods and Results MEDLINE, Ovid SP, and Embase were searched from the inception of these databases till August 2016. Randomized controlled trials that compared high doses of ACEI or ARB against low doses among patients with HF with reduced ejection fraction were included. Pooled analysis was done using a random-effects model, and quality of the studies was assessed by JADAD scale. The main outcomes were all-cause mortality and drug discontinuation. A total of 6 studies (4841 patients in low-dose and 4330 patients in high-dose groups) were included. Compared with low dose, high-dose ACEI or ARBs decreased all-cause mortality modestly (relative risk, 0.94; 95% confidence interval (CI), 0.89–1.00; P=0.05; I2=0%) and composite of HF hospitalizations and all-cause mortality (relative risk, 0.93; 95% CI, 0.87–1.00; P=0.04; I2=39.8%). No significant difference was found between the 2 groups in HF hospitalizations (relative risk, 0.94; 95% CI, 0.70–1.26; P=0.68; I2=52.8%) and all-cause hospitalizations (relative risk, 0.97; 95% CI, 0.85–1.11; P=0.67; I2=31.7%) risk. Discontinuation rates were also not significantly different in both groups (odds ratio, 1.13; 95% CI, 0.92–1.39; P=0.25; I2=32.6%). Conclusions In patients with HF with reduced ejection fraction, compared with lower doses, higher doses of ACEI and ARB significantly though modestly improved the composite end point of all-cause mortality or HF hospitalization without significantly increasing the chances of discontinuation.