ISSUE1575
In our Drugs for Chronic Heart Failure article,1 our description of the PARADIGM-HF trial comparing the combination of the ARB valsartan and the neprilysin inhibitor sacubitril (Entresto) with the ACE inhibitor enalapril for treatment of heart failure with reduced ejection fraction (HFrEF) characterized the dosage of enalapril as "suboptimal". Some readers have objected to that characterization.
The FDA-approved dosage of enalapril for treatment of HFrEF is 2.5-20 mg twice daily. In PARADIGM-HF, the dosage was capped at 10 mg twice daily, a widely used dosage that has been shown to reduce mortality in patients with HFrEF.2 In the trial, the rate of death from cardiovascular causes or hospitalization for heart failure was significantly lower with the combination of valsartan and sacubitril than with enalapril 10 mg twice daily (21.8% vs 26.5%). Whether allowing titration to 20 mg twice daily would have changed that result is a reasonable question, but there is no direct evidence that the higher dosage is more effective for this indication.3 We have removed the word "suboptimal" from the article as it appears online.
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