HFrEF: Similar Effects With Below-Target and Target Enalapril Doses

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Patients with heart failure with reduced ejection fraction who do not tolerate a high enalapril dose may still benefit from lower doses.
Patients with heart failure with reduced ejection fraction who do not tolerate a high enalapril dose may still benefit from lower doses.

Below-target and target doses of enalapril demonstrate similar clinical effects in patients with heart failure with reduced ejection fraction (HFrEF), according to a subanalysis of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial published in the European Journal of Heart Failure.

In the SOLVD Treatment trial, a total of 2569 patients with HFrEF with an EF ≤35% were randomly assigned to receive either a below-target dose of 5 to 10 mg/d enalapril (n=1285) or placebo (n=1284). At 1 month after randomization, researchers titrated up to a target enalapril dose of 20 mg/d in both groups (n=2458). Investigators of this subanalysis evaluated outcomes in these patients to identify rate differences in all-cause mortality and HF hospitalization or a combined end point for both.

At 4-year follow-up of patients who achieved up-titration dose (n=1444), a 9% lower risk for the combined end point with the target enalapril dose vs the target placebo dose was observed (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.60-0.81; P <.001).

In addition, a below-target dose of enalapril correlated with a 12% reduced risk for the combined end point vs the below-target placebo dose (mean dose for both, 8.8 mg/d) in 1014 patients (aHR, 0.68; 95% CI, 0.57-0.81; P <.001).

Target and below-target doses of enalapril, however, had no significant association with the combined end point (aHR, 1.04; 95% CI, 0.87-1.23; P =.695), demonstrating similar clinical effects in patients with HFrEF.

Although the use of higher angiotensin-converting-enzyme inhibitor doses may increase the chance for adverse effects, the investigators of this analysis suggest that higher doses of enalapril may "preclude the initiation or up-titration of beta-blockers and aldosterone antagonists."

The researchers concluded that "incremental clinical benefits associated with a higher dose [of enalapril], if present, are modest."

Reference

Lam PH, Dooley DJ, Fonarow GC, et al. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial. Eur J Heart Fail [published online October 5, 2017]. doi:10.1002/ejhf.937

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