A 2016 network meta-analysis evaluated the comparative efficacy and safety of five angiotensin-converting enzyme inhibitors (ACEIs)—captopril, enalapril, lisinopril, ramipril, and trandolapril—in patients with chronic heart failure classified as New York Heart Association (NYHA) class II or III. Randomized controlled trials (RCTs) published until November 2014 were identified. A total of 29 RCTs encompassing 2,099 participants met eligibility criteria and were included in the analysis. Surface under the cumulative ranking (SUCRA) probabilities were calculated to rank interventions, and sensitivity analyses excluded studies at high risk of bias. The Cochrane risk of bias tool was used to evaluate study quality. Across the network, ramipril was associated with the lowest all-cause mortality, while lisinopril demonstrated significantly higher odds of all-cause mortality compared to both placebo (odds ratio [OR] 65.9, 95% credible interval [CrI] 1.91 to 239.6) and ramipril (OR 14.65, CrI 1.23 to 49.5). Enalapril was most effective at improving left ventricular ejection fraction, stroke volume, and reducing mean arterial pressure, but carried the highest incidence of cough (OR 274.4, CrI 2.4 to 512.9), gastrointestinal discomfort, and renal function deterioration. Sensitivity analyses confirmed the robustness of the findings, and meta-regression for age did not show significant effect modification. These findings underscore the nuanced risk-benefit profiles among ACEIs, with enalapril offering hemodynamic advantages at the expense of tolerability and lisinopril demonstrating comparatively unfavorable outcomes in this heart failure population. [1]
A 2023 network meta-analysis systematically evaluated the relative risk of cough associated with ACEIs compared to placebo, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). This comprehensive review synthesized data from 135 RCTs encompassing 45,420 patients across a diverse clinical population, including individuals with hypertension, heart failure, proteinuria, and coronary artery disease. Eleven ACEIs were analyzed individually and as a class. The analysis incorporated direct and indirect comparisons using a network meta-analytic framework, with SUCRA values employed to quantify the likelihood of each agent inducing cough. The pooled relative risk of ACEI-induced cough compared to placebo was 2.21 (95% confidence interval [CI] 2.05 to 2.39. Lisinopril demonstrated a 64.7% probability of inducing cough along with enalapril, which came in at 49.7%. Additionally, ACEI-induced cough was identified as a frequent cause of treatment discontinuation, particularly with perindopril, ramipril, and enalapril. [2]
According to a Cochrane review published in 2008, which evaluated the blood pressure lowering efficacy of ACEIs for primary hypertension, enalapril results in a near maximal trough systolic blood pressure (SBP) lowering and near maximal trough diastolic blood pressure (DBP) lowering of -8.66 (95% CI -10.48 to -6.84), and -4.80 (95% CI -5.81 to -3.79), respectively. Comparatively, lisinopril results in a near maximal trough SBP lowering and near maximal trough DBP lowering of -8.00 (95% CI -10.14 to -5.85) and -4.76 (95% CI -5.92 to -3.60), respectively. The effects of lisinopril and enalapril were not directly compared within a meta-analysis. [3]