Very low-dose sacubitril/valsartan feasible for HFrEF patients with drug intolerance

Initiation of treatment with low doses of sacubitril/valsartan (SV) appears to be effective for heart failure with reduced ejection fraction (HFrEF) even in patients suspected to be intolerant to the drug regimen, according to a recent study. Low-dose SV results in comparable changes in N-terminal brain natriuretic peptide (NT-proBNP) as its standard dose counterpart.

Researchers enrolled 106 HFrEF patients who were initiated on a very low dose (VLD) of SV (25 mg twice daily), with subsequent uptitration. A parallel group of 100 patients on standard SV dose was also included. All participants were deemed by their physicians to be potentially intolerant to SV.

Outcomes included tolerability, determined by the incidence of adverse events including symptomatic hypotension as well as the proportion of patients achieving the maximal target dose without adverse events. The principal clinical outcome was a composite of cardiovascular mortality or HF rehospitalization.

Discontinuation of SV was comparable between the VLD and standard dose groups (5.7 percent vs 7.0 percent; p=0.693). Hypotension was the most common adverse event, developing in 21.7 percent and 16.0 percent of the VLD and standard-dose patients, respectively, with no significant between-group difference (p=0.297). The same was true for symptomatic hypotension (p=0.204).

In terms of clinical efficacy, 27 cases of the primary composite outcomes occurred during follow-up, including four deaths and 23 rehospitalizations. No between-group difference in incidence was reported.

Following SV treatment, the VLD group saw an increase in systolic blood pressure, while the standard-dose arm saw a corresponding decrease; the between-group difference was significant (p=0.014). Nevertheless, other endpoints, such as NT-proBNP and left ventricular ejection fraction, did not differ between arms.