Sacubitril/valsartan maintains efficacy, safety in HF patients with hypotension

Both symptomatic and asymptomatic hypotension are associated with worse outcomes during treatment with either enalapril or sacubitril/valsartan, but the benefits derived from the combination therapy are maintained or even improved in heart failure (HF) patients with hypotension, a study has shown.

A post hoc analysis of PARADIGM-HF was conducted to compare the efficacy and safety of sacubitril/valsartan with enalapril using time-updated Cox proportional hazard models. Cardiovascular death or HF hospitalization was the primary outcome.

Of the 8,399 patients in PARADIGM-HF, 1,343 (16.0 percent) had only asymptomatic hypotension and 936 (11.1 percent) had symptomatic hypotension at least once after randomization.

The symptomatic hypotension group were older and more frequently had cardiovascular comorbidities than the asymptomatic group, whereas patients with asymptomatic hypotension had lower left ventricular ejection fraction. Those who had either hypotension type were at increased risk for all outcomes examined.

However, the effect of sacubitril/valsartan on the primary outcome did not diminish in patients with hypotension relative to those who had no hypotension. Compared with enalapril, sacubitril/valsartan had HR of 0.80 (95 percent confidence interval [CI], 0.72–0.89) for no hypotension, 0.87 (95 percent CI, 0.70–1.08) for asymptomatic hypotension, and 0.51 (95 percent CI, 0.38–0.69) for symptomatic hypotension (p=0.01 for interaction).

The same trend was observed for cardiovascular and all-cause deaths.

Use of sacubitril/valsartan versus enalapril remained safe regardless of the occurrence of hypotension. In addition, treatment discontinuation occurred more frequently in enalapril- than sacubitril/valsartan-treated patients experiencing symptomatic and asymptomatic hypotension.