Sacubitril/Valsartan Reduces All-Cause Hospitalizations in Heart Failure Patients with Low LVEF: JAMA

A new study from the PARADIGM-HF and PARAGON-HF clinical trials found that sacubitril/valsartan significantly reduced the risk of hospitalization for any cause, particularly in patients with below-normal left ventricular ejection fraction (LVEF). The trial which is a post-hoc analysis was published in the journal JAMA Cardiology and was conducted from February to April 2024. The trial results shed light on the broader benefits of this drug beyond its known effects on heart failure-related outcomes.

In chronic heart failure (HF) conditions, Sacubitril/valsartan can be used to reduce the risk of cardiovascular death or hospitalization. This is of particular advantage in patients with patients having left ventricular ejection fraction (LVEF) below normal. As most of the patents are older with comorbid diseases, the risk of hospitalization unrelated to HF is high. As there is ambiguity on the use of sacubitril/valsartan on all-cause hospitalizations (ACH), researchers conducted a post-hoc analysis of the PARADIGM-HF and PARAGON-HF randomized clinical trials to assess the effects of sacubitril/valsartan on ACH and the main causes of hospitalization. 

The analysis combined data from two major randomized clinical trials including 13,194 participants with an average of 67 years and having chronic HF. These patients had varying degrees of left ventricular function, with LVEF ≤40% in the PARADIGM-HF trial and LVEF ≥45% in the PARAGON-HF trial. The participants were New York Heart Association class II to IV HF symptoms and elevated natriuretic peptides, markers of heart stress were randomized to receive either sacubitril/valsartan or a renin-angiotensin system inhibitor (RASi) such as enalapril or valsartan.The primary outcome examined was all-cause hospitalization (ACH) and cause-specific hospitalizations, analyzed using Cox proportional hazards models.

Findings:

• Sacubitril/valsartan demonstrated a statistically significant reduction in ACH compared to RASi over a median follow-up of 2.5 years.
• Patients on sacubitril/valsartan had an incidence rate of 25 hospitalizations per 100 patient-years, while those on RASi had an incidence rate of 27 per 100 patient-years.
• This translated into an absolute risk reduction (ARR) of 2.1 hospitalizations per 100 patient-years and a number needed to treat (NNT) of 48 patient-years to prevent one ACH.
• Importantly, this reduction in hospitalizations was mainly driven by fewer cardiac and pulmonary admissions in the sacubitril/valsartan group, while non-cardiac hospitalizations remained similar between the two treatment groups.
• The effect of sacubitril/valsartan appeared to vary based on LVEF. Patients with LVEF below 60% saw the most pronounced benefits (hazard ratio [HR], 0.91), while those with LVEF above 60% experienced no significant advantage (HR, 0.97).

The study suggests that sacubitril/valsartan could have a broader protective effect on patients with chronic HF, especially those with lower LVEF, by reducing the risk of hospitalization from cardiac and pulmonary causes. The findings are particularly relevant for older patients with multiple comorbidities, who are at higher risk for hospitalization for reasons other than HF.

Further reading: Lu H, Claggett BL, Packer M, et al. Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure: Post Hoc Analysis of the PARADIGM-HF and PARAGON-HF Randomized Clinical Trials. JAMA Cardiol. Published online August 30, 2024. doi:10.1001/jamacardio.2024.2566