Estimating lifetime benefits of comprehensive disease -modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Vaduganathan, M (Author) Other; Claggett, BL (Author) Other; Jhund, PS (Author) Other; Cunningham, JW (Author) Other; Ferreira, JP (Author) FMUP; Zannad, F (Author) Other; Packer, M (Author) Other; Fonarow, GC (Author) Other; McMurray, JJV (Author) Other; Solomon, SD (Author) Other

Journal

Title: The Lancet

Vol. 396

Pages: 121-128

ISSN: 0140-6736

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 123 Citations

Scopus - 131 Citations

Other information

Authenticus ID: P-00S-8WF

DOI: 10.1016/s0140-6736(20)30748-0

Abstract (EN): Background Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and beta blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF. Methods In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, beta blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and beta blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and beta blocker). Findings The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0.38 (95% CI 0.30-0.47). HRs were also favourable for cardiovascular death alone (HR 0.50 [95% CI 0.37-0.67]), hospital admission for heart failure alone (0.32 [0.24-0.43]), and all-cause mortality (0.53 [0.40-0.70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2.7 additional years ( for an 80-year-old) to 8.3 additional years ( for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1.4 additional years (for an 80-year-old) to 6.3 additional years (for a 55-year-old) of survival compared with conventional therapy. Interpretation Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, beta blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard.

Language: English

Type (Professor's evaluation): Dissemination

No. of pages: 8