Combinations of ARNI+BB+MRA and ACEI+BB+MRA+IVA were the most effective therapies for HFrEF, reducing all-cause mortality versus placebo by 62% (HR 0.38; CrI 0.20-0.65) and 59%, respectively.
Meta-Analysis
Do combinations of recommended drug therapies improve mortality and hospitalization outcomes in patients with HFrEF compared to single agents or placebo?
Combinations of disease-modifying therapies, particularly ARNI+BB+MRA, provide incremental and substantial benefits in reducing mortality and hospitalizations in HFrEF, supporting current guideline recommendations.
Hazard Ratio: 0.38 (95% CI 0.2–0.65)
AIMS: A network meta-analysis (NMA) of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including their combinations, was performed to assess the relative efficacy and incremental benefit. METHODS AND RESULTS: A search was made in biomedical databases for randomized controlled trials published between 1987 and 2017 on angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor-neprilysin inhibitors (ARNI). A total of 58 relevant trials were identified. The relative efficacy of each treatment group (or combination) in terms of all-cause mortality, cardiovascular mortality, all-cause hospitalizations and hospitalizations for heart failure, per patient-year of follow-up, were combined in a random-effects Bayesian NMA. The pairwise comparison between each regimen and for each outcome was estimated. The NMA was dominated by 15 large-scale trials with between 1984 and 18 898 patient-years of follow-up. Combinations of drug groups showed incremental benefits on outcomes over single groups. The most effective combinations were ARNI+BB + MRA and ACEI+BB + MRA + IVA, showing reductions in all-cause mortality (vs. placebo) of 62% and 59%, respectively; hazard ratios were 0.38 credible interval (CrI) 0.20-0.65 and 0.41 (CrI 0.21-0.70); and in all-cause hospitalizations with reductions of 42% for both. These two combinations were also the most effective for the other outcomes studied. CONCLUSION: Our analysis shows that the incremental use of combinations of disease-modifying therapies has resulted in the progressive improvement in mortality and hospitalization outcomes in HFrEF. Our findings support the current guideline recommendations.
Komajda et al. (Mon,) conducted a meta-analysis in heart failure with reduced ejection fraction (HFrEF). ARNI+BB+MRA and ACEI+BB+MRA+IVA vs. Placebo was evaluated on all-cause mortality (HR 0.38, 95% CI 0.20-0.65). Combinations of ARNI+BB+MRA and ACEI+BB+MRA+IVA were the most effective therapies for HFrEF, reducing all-cause mortality versus placebo by 62% (HR 0.38; CrI 0.20-0.65) and 59%, respectively.