Does sacubitril-valsartan lead to reduced rates of hospitalizations and death for CHF compared to valsartan alone in patients with HFpEF?
Study design: Multinational, double-blind, randomized, parallel group, active-controlled trial
Population
- Number of patients studied: 4,822
- Inclusion criteria: Age ≥50 years, LVEF ≥45%, NYHA class II-IV symptoms, structural heart disease, elevated natriuretic peptide levels
- Exclusion criteria: Prior LVEF <40%, acute coronary syndrome or cardiac intervention within 3 months, acute decompensated HF, uncontrolled hypertension or hypotension, severe pulmonary disease, hemoglobin <10 g/dl, BMI >40 kg/m2, etc.
Primary outcome: Composite of HF hospitalization and CVD mortality - RR 0.87 (95% CI 0.75-1.01)
Secondary Outcomes
- Change in NYHA class at 8 months - OR 1.45 (95% CI 1.13-1.86)
- Change in KCCQ clinical summary score at 8 months - Difference 1.0 (95% CI 0.0-2.1)Renal composite outcome - HR 0.50 (95% CI 0.33-0.77)
- All-cause mortality - HR 0.97 (95% CI 0.84-1.13)
Safety Outcomes
| Adverse Event | Sacubitril-Valsartan | Valsartan |
|---|---|---|
| Hypotension | 14.0% | 9.2% |
| Angioedema | 0.2% | 0.1% |
| Increased serum creatinine | 16.1% | 15.2% |
| Increased serum potassium | 6.3% | 5.6% |
| Cough | 11.3% | 12.1% |
Conclusions
The combination of sacubitril-valsartan did not lead to a significantly lower composite outcome of total hospitalizations for heart failure and death from cardiovascular causes when compared to valsartan alone in patients with symptomatic HFpEF. However, there was a modest improvement in NYHA class and less decline in renal function.