Physicians' Academy for Cardiovascular Education

HFrEF patients with low SBP do tolerate target dose of ARNI

Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study

Senni M, McMurray JJV, Wachter R, et al. - Eur J Heart Fail 2017; published online ahead of print


Treatment with sacubitril/valsartan, at target doses, significantly reduces CV death, HF hospitalization, and all-cause mortality compared with enalapril, in patients with HFrEF [1]. Due to its dual mode of action, the sacubitril/valsartan combination induces greater BP reductions compared with ACEIs and ARBs, which may restrict its routine use in HFrEF patients with low SBP. Low SBP is associated with a poor prognosis and in a recent analysis from the Systolic Heart Failure Treatment trial, every 10-mmHg lower baseline SBP was associated with a 12% higher risk for all-cause mortality in patients with chronic HFrEF [2-4].

In this post hoc analysis of the TITRATION study [5], the relationship between SBP at screening and successful initiation and up-titration of sacubitril/valsartan was evaluated in HFrEF patients. Randomized patients were divided in the following 4 SBP groups at screening: 100–110 mmHg; 111–120 mmHg; 121–139 mmHg; and ≥140 mmHg. In each SBP group, treatment success was defined as the proportion of patients achieving and maintaining the sacubitril/valsartan target dose of 97 mg/103 mg twice per day without any dose interruption or down-titration for 12 weeks. Moreover, the tolerability success was defined as the proportion of patients that tolerated sacubitril/valsartan 97 mg/103 mg twice per day for at least the final 2 weeks leading to study completion, regardless of previous dose interruption or down-titration.

Main results


In a post hoc analysis of the TITRATION study, the majority of patients with low SBP levels at screening tolerated the initiation/up-titration to target dose level of sacubitril/valsartan using a gradual up-titration regimen. These findings suggest that low screening SBP levels should not prevent clinicians from considering the initiation of sacubitril/valsartan.


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Find this article online at Eur J Heart Fail