Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients
Key result
LCZ696 cuts cardiovascular death ~20% vs. enalapril in chronic heart failure.
- HR 0.80
- 95% CI 0.72-0.89
- P<0.001
- n=8,399
Why the study?
To more completely understand the components of the mortality benefit observed with LCZ696 compared with enalapril, the authors examined its effect on mode of death.
Does sacubitril/valsartan (LCZ696) reduce specific modes of death compared with enalapril in patients with chronic heart failure and reduced ejection fraction?
Key Points
- This research aims to evaluate how the angiotensin-receptor-neprilysin inhibitor LCZ696 affects the mode of death in heart failure compared to enalapril.
- Prospective, double-blind, randomized trial with 8399 patients having chronic heart failure.
- Median follow-up of 27 months with adjudication of mode of death by a blinded committee.
- Comparison of mortality outcomes between LCZ696 and enalapril.
- LCZ696 reduced the risk of cardiovascular death (HR 0.80, 95% CI 0.72-0.89, P < 0.001).
- Sudden cardiac death was reduced by LCZ696 (HR 0.80, 95% CI 0.68-0.94, P = 0.008).
- Deaths from worsening heart failure were also reduced (HR 0.79, 95% CI 0.64-0.98, P = 0.034).
Study Design
Type
RCT (n=8,399)
Blinding
double-blind
Randomization
randomized
Structured PICO
Does sacubitril/valsartan (LCZ696) reduce specific modes of death compared with enalapril in patients with chronic heart failure and reduced ejection fraction?
P
Population
8,399 patients with chronic heart failure, NYHA Class II-IV symptoms, and LVEF ≤40% receiving guideline-recommended medical therapy, followed for a median of 27 months.
I
Intervention
Sacubitril/valsartan (LCZ696)
C
Comparator
Enalapril
O
Outcome
Mode of death (including cardiovascular death, sudden cardiac death, and death due to worsening heart failure), adjudicated by a blinded clinical endpoints committeehard clinical
Main Result
Hazard Ratio: 0.8 (95% CI 0.72–0.89)
p-value: p=< 0.001
Ask about this paper
Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This robust finding provides strong evidence supporting use of LCZ696 as the treatment of choice for heart failure instead of an ACE inhibitor or ARB.”
“I would say 9 to 10 that angiotensin-receptor neprilysin inhibition will be the cornerstone of treatment for patients with chronic heart failure and a reduced ejection fraction, replacing the current use of ACE inhibitors and angiotensin-receptor blockers.”
“This is the first study in a long time where we saw not only a reduction in the combined endpoint of cardiovascular death and hospitalization, but also significant effect on each of these two endpoints individually as well as on all-cause mortality.”
Implication
In patients with HFrEF, sacubitril/valsartan reduces both sudden cardiac death and death from worsening heart failure compared to enalapril.
Abstract
AIMS: The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death. METHODS AND RESULTS: PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths. CONCLUSIONS: LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, NCT01035255.
Discussion
No takes yet. Share an insight, caveat, or question.
Cite This Study
Desai et al. (2015) conducted an RCT in chronic heart failure (n=8,399). LCZ696 vs. enalapril was evaluated on cardiovascular death (HR 0.80, 95% CI 0.72-0.89, p=< 0.001). LCZ696 significantly reduced the risk of cardiovascular death compared with enalapril in patients with chronic heart failure (HR 0.80; 95% CI 0.72-0.89; P<0.001).