Disease-modifying drugs significantly improve HF survival

Vaduganathan M, Claggett BL, Jhund PS et al (2020) 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. Lancet 21 May [epub ahead of print]

• Heart failure with reduced ejection fraction (HFrEF) is often treated with conventional neurohormonal therapy consisting of ACE inhibitors, angiotensin receptor blockers and beta-blockers. Disease-modifying drugs target multiple mechanistic pathways involved in HFrEF and therefore offer greater reductions in mortality but are infrequently prescribed.
• This paper used data from the PARADIGM-HF, DAPA-HF and EMPHASIS-HF trials to estimate lifetime gains in event-free survival and overall survival with comprehensive disease-modifying treatment (mineralocorticoid receptor agonists, angiotensin receptor–meprilysin inhibitors and sodium/glucose cotransporter 2 inhibitors) versus conventional therapy in individuals with chronic HFrEF.
• In order to calculate incremental long-term gains resulting from the different treatments, researchers assumed the relative effects of treatment were consistent over time.
• Comprehensive disease-modifying therapy resulted in a greater reduction in the primary endpoint of the composite of cardiovascular death or first hospitalisation for heart failure when compared to conventional therapy (hazard ratio 0.38). Compared to conventional therapy, comprehensive treatment also led to improvements in the secondary endpoints of cardiovascular death (hazard ratio 0.5), admission for heart failure (hazard ratio 0.32) and all-cause mortality (hazard ratio 0.53).
• The authors estimated that comprehensive treatment conferred an additional 8.3 years free from first hospitalisation for heart failure or cardiovascular death and 6.3 years’ additional survival in 55-year-olds. For 80-year-olds, these benefits were 2.7 years and 1.4 years, respectively.
• Previous research estimated that, compared to placebo, conventional treatment reduces the hazard of death by 43–53%; this research estimates that optimising comprehensive disease-modifying therapy lowers admission for heart failure or cardiovascular death by over 60%. This translates into an absolute risk reduction of 18–25% and number needed to treat of four to six over a 3-year period.
• The authors conclude that the data support the use of disease-modifying therapy to halt or delay the progression of HFrEF and extend survival. They advocate urgent implementation strategies to facilitate multidrug prescribing – particularly the addition of sodium/glucose cotransporter 2 inhibitors – in selected HFrEF patients.

 
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