New Haven, CT—For more than 4 decades, the standard of care for acute decompensated heart failure, which accounts for more than a million hospitalizations in the United States annually, has remained essentially unchanged.
A study in the New England Journal of Medicine discusses how, despite multiple trials of promising therapies, the standard of care still consists of decongestion with IV diuretics and hemodynamic support with vasodilators and inotropes.
The PIONEER-HF trial, led by Yale University School of Medicine researchers, set out to determine whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for the critical condition.
To determine that, the study team enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive either sacubitril-valsartan—target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily in 440 patients, or enalapril—target dose, 10 mg twice daily in 441 patients.
The time-averaged proportional change in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration from baseline through Weeks 4 and 8 was defined as the primary efficacy outcome, while researchers also monitored safety outcomes such as rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.
Results indicate that the time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group. Specifically, the study notes, the ratio of the geometric mean of values obtained at Weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group versus 0.75 in the enalapril group—percent change, -46.7% versus -25.3%; ratio of change with sacubitril-valsartan versus enalapril, 0.71; 95% confidence interval [CI], 0.63-0.81; P <.001).
Researchers point out that the greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as Week 1 (ratio of change, 0.76; 95% CI, 0.69-0.85). They add, however, that rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.
“Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy,” study authors conclude. “Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.”
The findings are significant because of the high rates of short-term unplanned rehospitalization and death associated with acute decompensated heart failure—21% and 12%, respectively.
In the earlier PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, the use of sacubitril-valsartan, an angiotensin receptor–neprilysin inhibitor, resulted in a lower risk of death from cardiovascular causes or hospitalization for heart failure than the use of enalapril in this population.
Eligible for the PARADIGM-HF trial were ambulatory outpatients who had received an angiotensin-converting–enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB), at stable doses equivalent to a dose of enalapril of 10 mg daily, for a minimum of 4 weeks. The trial also had sequential run-in periods during which all patients received high-dose enalapril and sacubitril–valsartan before they underwent randomization.
Patients with acute decompensated heart failure, which was defined by the presence of signs and symptoms that may lead to the use of intravenous therapy, were excluded from that trial.
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A study in the New England Journal of Medicine discusses how, despite multiple trials of promising therapies, the standard of care still consists of decongestion with IV diuretics and hemodynamic support with vasodilators and inotropes.
The PIONEER-HF trial, led by Yale University School of Medicine researchers, set out to determine whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for the critical condition.
To determine that, the study team enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive either sacubitril-valsartan—target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily in 440 patients, or enalapril—target dose, 10 mg twice daily in 441 patients.
The time-averaged proportional change in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration from baseline through Weeks 4 and 8 was defined as the primary efficacy outcome, while researchers also monitored safety outcomes such as rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.
Results indicate that the time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group. Specifically, the study notes, the ratio of the geometric mean of values obtained at Weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group versus 0.75 in the enalapril group—percent change, -46.7% versus -25.3%; ratio of change with sacubitril-valsartan versus enalapril, 0.71; 95% confidence interval [CI], 0.63-0.81; P <.001).
Researchers point out that the greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as Week 1 (ratio of change, 0.76; 95% CI, 0.69-0.85). They add, however, that rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.
“Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy,” study authors conclude. “Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.”
The findings are significant because of the high rates of short-term unplanned rehospitalization and death associated with acute decompensated heart failure—21% and 12%, respectively.
In the earlier PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, the use of sacubitril-valsartan, an angiotensin receptor–neprilysin inhibitor, resulted in a lower risk of death from cardiovascular causes or hospitalization for heart failure than the use of enalapril in this population.
Eligible for the PARADIGM-HF trial were ambulatory outpatients who had received an angiotensin-converting–enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB), at stable doses equivalent to a dose of enalapril of 10 mg daily, for a minimum of 4 weeks. The trial also had sequential run-in periods during which all patients received high-dose enalapril and sacubitril–valsartan before they underwent randomization.
Patients with acute decompensated heart failure, which was defined by the presence of signs and symptoms that may lead to the use of intravenous therapy, were excluded from that trial.
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