Comparative Efficacy and Safety of Novel Therapeutic Drugs for Chronic Heart Failure: A Systematic Review and Network Meta-Analysis

Recently, several novel therapeutic drugs (NTDs) were found to have therapeutic potential in treating chronic heart failure (CHF). This network meta-analysis aimed to compare and rank different NTDs in patients with CHF. We searched Medline/PubMed, Embase and Cochrane Library of Clinical Trials database through February 9, 2021, for RCTs comparing the NTDs with standard of care (SOC) in adult patients with CHF. Trials of angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose transporter 2 (SGLT2) inhibitors, ivabradine, non-steroidal mineralcorticoid receptor antagonists (MRA), soluble guanylate cyclase (SGC) stimulators and cardiac myosin activators (CMA) were included. We performed a Bayesian network meta-analysis to indirectly compare the mortality, HF hospitalization and adverse events of the NTDs. Thirty-three studies enrolling 63614 patients were included in this analysis. The results showed none of the NTDs was associated with a significant superiority in reducing all-cause mortality, composite outcome of cardiovascular mortality or HF hospitalization and HF hospitalization alone. For cardiovascular mortality alone, ARNI was superior to ivabradine and CMA, while SGLT2 inhibitors were superior to CMA. For adverse events, SGLT2 inhibitors were associated with a lower risk of serious adverse events than ivabradine and CMA. ARNI and SGLT2 inhibitors were recommended as better choices in reducing CV mortality, while SGLT2 inhibitors performed better regarding serious adverse event.