Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial.

Abstract

BACKGROUND:

Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction.

METHODS:

PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms.

RESULTS:

Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30).

CONCLUSIONS:

Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

• Authors: Akshay S Desai, Muthiah Vaduganathan, John G Cleland, Brian L Claggett, Ebrahim Barkoudah, Peter Finn, Finnian R McCausland, Mehmet B Yilmaz, Martin Lefkowitz, Victor Shi, Marc A Pfeffer, John J V McMurray, Scott D Solomon
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 14 Issue 12 Pg. e008597 (12 2021) ISSN: 1941-3297 [Electronic] United States
• PMID: 34807713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Biphenyl Compounds
• Tetrazoles
• sacubitril

Topics

• Aged
• Aminobutyrates (therapeutic use)
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Cause of Death
• Female
• Heart Failure (drug therapy, mortality, physiopathology)
• Humans
• Male
• Middle Aged
• Stroke Volume (drug effects)
• Tetrazoles (therapeutic use)
• Ventricular Function, Left (drug effects)