Comparative efficacy of novel drugs as an addition to guideline-directed medical therapy for heart failure with reduced ejection fraction: a network meta-analysis of randomised controlled trials

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is the global public health burden a prevalence of 1% adults. The current guidelines suggest use angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), mineralocorticoid antagonists (MRA), receptor-neprilysin (ARNIs), and sodium-glucose cotransporter-2 (SGLT2i) to reduce mortality. Soluble guanylyl cyclase (sGC) omecamtiv mecarbil (OMM) have also been studied in HFrEF. However, there has no head-to-head comparison efficacy cumulative incidence interpretation outcome novel drugs. Purpose To compare all drugs possible combinations guideline-directed medical therapy (GDMT) including ACEI, ARB, BB, MRA, ivabradine (IVA), ARNI, SGLT2i, sGC OMM find best additional drug GDMT. Methods This network meta-analysis (MA) part study registered on PROSPERO (CRD42021262029). A systematic search MAs randomised controlled trials (RCT) was performed biomedical databases from inception June 2021. All RCTs were selected against eligibility criteria. primary composite or cardiovascular death heart hospitalisation focus. In addition, secondary outcomes, i.e., analysed. Individual patient data constructed Kaplan-Meier-extracted data; then studies combined. mixed-effect parametric survival model accelerated time used, considering individual as random effects treatments fixed-effect. Median for each regimen hazard ratios (HR) comparing between regimens 95% confidence intervals (CI) estimated KM data. Results Cumulative displayed Figure 1. Compared GDMT ACEI+BB+MRA, BB+MRA+ARNI (HR 0.80, CI 0.74–0.88), ACEI+BB+MRA+IVA 0.82, 0.75–0.90), ACEI+BB+MRA+SGLT2i 0.75, 0.68–0.82), ACEI+BB+MRA+sGC 0.91, 0.83–0.99), ACEI+BB+MRA+OMM 0.92, 0.86–0.99) showed superior benefits. ACEI+BB 0.68, 0.59–0.79) ACEI+BB+ARB 0.81, 0.67–0.98) both statistically significantly inferior treatment combination highest risk reduction 25%. More details are provided 2. analysis outcomes corresponding trend reducing by 25% 0.68–0.82) versus Conclusion MA that SGT2i currently Funding Acknowledgement Type funding sources: Public hospital(s). Main source(s): Faculty Medicine Ramathibodi Hospital, Mahidol University