Abstract | BACKGROUND: METHODS: In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, β blocker, MRA, and SGLT2 inhibitor) versus conventional therapy ( ACE inhibitor or ARB and β 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 β 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, β blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard. FUNDING: None.
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Authors | Muthiah Vaduganathan, Brian L Claggett, Pardeep S Jhund, Jonathan W Cunningham, João Pedro Ferreira, Faiez Zannad, Milton Packer, Gregg C Fonarow, John J V McMurray, Scott D Solomon |
Journal | Lancet (London, England)
(Lancet)
Vol. 396
Issue 10244
Pg. 121-128
(07 11 2020)
ISSN: 1474-547X [Electronic] England |
PMID | 32446323
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
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Copyright | Copyright © 2020 Elsevier Ltd. All rights reserved. |
Chemical References |
- Adrenergic beta-Antagonists
- Angiotensin Receptor Antagonists
- Angiotensin-Converting Enzyme Inhibitors
- Mineralocorticoid Receptor Antagonists
- Sodium-Glucose Transporter 2 Inhibitors
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Topics |
- Adrenergic beta-Antagonists
(therapeutic use)
- Aged
- Aged, 80 and over
- Angiotensin Receptor Antagonists
(therapeutic use)
- Angiotensin-Converting Enzyme Inhibitors
(therapeutic use)
- Death
- Drug Therapy, Combination
(methods, statistics & numerical data)
- Female
- Heart Failure
(drug therapy, mortality, physiopathology)
- Hospitalization
(statistics & numerical data)
- Humans
- Male
- Middle Aged
- Mineralocorticoid Receptor Antagonists
(therapeutic use)
- Progression-Free Survival
- Sodium-Glucose Transporter 2 Inhibitors
(therapeutic use)
- Stroke Volume
(drug effects, physiology)
- Treatment Outcome
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