Literature
Clinical Pearls & Morning Reports
Published October 23, 2019
How does sacubitril–valsartan compare to valsartan regarding the composite outcome of total hospitalizations and cardiovascular death in patients with heart failure and preserved ejection fraction?
Solomon et al. conducted the PARAGON-HF trial, which assessed the rate of a composite outcome of total hospitalizations for heart failure and death from cardiovascular causes with sacubitril–valsartan versus valsartan alone, in patients with heart failure and preserved ejection fraction. Eligibility requirements at screening included an age of 50 years or older, signs and symptoms of heart failure, New York Heart Association (NYHA) class II to IV, and an ejection fraction of 45% or higher within the previous 6 months. Read the Original Article here.
Clinical Pearls
Q: Is sacubitril–valsartan effective in patients with heart failure and reduced ejection fraction?
A: The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan resulted in a lower rate of hospitalization for heart failure or death from cardiovascular causes than enalapril among patients with heart failure and reduced ejection fraction (≤40%). In patients with heart failure and preserved left ventricular ejection fraction, sacubitril–valsartan resulted in a lower level of N-terminal pro–B-type natriuretic peptide, a larger reduction in left atrial size, and greater improvement in the NYHA functional class than valsartan.
Q: How does sacubitril–valsartan compare to valsartan regarding the composite outcome of total hospitalizations and cardiovascular death in patients with heart failure and preserved ejection fraction?
A: In the PARAGON-HF trial, the primary composite outcome of total hospitalizations for heart failure and death from cardiovascular causes did not differ significantly between the two groups. There were 894 primary events (690 hospitalizations for heart failure and 204 deaths from cardiovascular causes) in 526 patients in the sacubitril–valsartan group and 1009 primary events (797 hospitalizations for heart failure and 212 deaths from cardiovascular causes) in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06).
Morning Report Questions
Q: Was there a suggestion of heterogeneity of treatment effect regarding the primary outcome in the PARAGON-HF trial?
A: Patients with heart failure and preserved ejection fraction are phenotypically heterogeneous, and the data from the PARAGON-HF trial raise the possibility of a differential treatment effect in the broad population studied. Of the 12 prespecified subgroups, 2 showed possible heterogeneity of treatment effect, with a suggestion of benefit in patients with an ejection fraction in the lower part (45 to 57%) of the range studied and in women, who represent a high proportion of patients with heart failure with preserved ejection fraction and who were well represented in this trial.
Q: What were some of the safety outcomes in the PARAGON-HF trial?
A: After randomization, 610 patients (25.3%) in the sacubitril–valsartan group and 638 (26.7%) in the valsartan group discontinued the trial drug for reasons other than death, and 370 patients (15.4%) in the sacubitril–valsartan group and 387 (16.2%) in the valsartan group discontinued the trial drug because of an adverse event. Patients in the sacubitril–valsartan group were more likely to have hypotension but less likely to have increases in the creatinine and potassium levels than those in the valsartan group. Confirmed angioedema after randomization occurred in 14 patients in the sacubitril–valsartan group and in 4 patients in the valsartan group; no patients had airway compromise.