Treatment of HFrEF with Sacubitril/Valsartan Does Not Have to Be the ‘Last Resort’
The TRANSITION study has provided evidence on the safety and efficacy of administering sacubitril/valsartan to patients after acute decompensation of chronic heart failure with reduced ejection fraction of the left ventricle (HFrEF). A recent sub-analysis of its results suggested that not only patients with a long-known diagnosis but also those with newly diagnosed HFrEF could benefit from the treatment if the possibility of its prescription in this indication arises.
Indications for Sacubitril/Valsartan
Sacubitril/valsartan is the first approved representative of a new group of drugs, inhibitors of neprilysin and the angiotensin receptor. It is indicated for the treatment of patients with HFrEF, replacing angiotensin-converting enzyme inhibitors (ACEi) and AT1 receptor blockers for angiotensin II (sartans)—according to current guidelines, only in patients who remain symptomatic after exhausting all previous pharmacological options.
The PARADIGM-HF study demonstrated a 20% reduction in deaths from cardiovascular causes and hospitalizations for heart failure when administered in outpatient care compared to enalapril. The TRANSITION and PIONEER-HF studies also demonstrated its effect on improving the prognosis of patients after acute decompensation of HFrEF. However, it was not yet clear whether the benefit from sacubitril/valsartan treatment depends on the “age” of the HFrEF diagnosis at the time therapy is initiated.
The TRANSITION Study and Subgroup Analysis
The TRANSITION study randomized patients hospitalized for an episode of acute decompensation of chronic heart failure into 2 groups: in the first group, sacubitril/valsartan administration was initiated ≥ 12 hours before discharge from the hospital, and in the second group, treatment was started between the 1st and 14th day after discharge. The proportion of patients who reached the target dose of 97/103 mg 2× daily after 10 weeks of use was evaluated, and no statistically significant difference was found between the groups. Both methods of initiating sacubitril/valsartan therapy were well tolerated.
In the study’s sub-analysis, the incidence of adverse events, serious adverse events, and treatment tolerability were compared in patients with a history of HFrEF before hospitalization (n = 705) versus the group where chronic heart failure was newly diagnosed, representing the first episode (n = 286).
Findings
In the group with de novo HFrEF diagnosis, a larger proportion of patients reached the target dose of sacubitril/valsartan after 10 weeks of use (56 vs. 45%; relative risk [RR] 1.30; 95% confidence interval [CI] 1.12–1.52; p < 0.001), indicating better treatment tolerability in this group. Conversely, serious adverse events were less frequent in the de novo diagnosis group, and a smaller proportion of these patients permanently discontinued sacubitril/valsartan treatment. Newly diagnosed patients also experienced a faster and more significant decrease in levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T. They also exhibited fewer rehospitalizations for heart failure or any cause.
Conclusion
This subgroup analysis of the TRANSITION study demonstrated that initiating sacubitril/valsartan therapy in patients with newly diagnosed heart failure with reduced ejection fraction (after its acute decompensation) offers an even better efficacy and safety profile than in patients with a long-known diagnosis. Early initiation of therapy with this combined preparation can therefore be considered a protective factor in terms of disease progression. However, even in patients with a long-diagnosed disease, early administration of sacubitril/valsartan, ideally during hospitalization following an episode of HFrEF decompensation, is a well-tolerated therapeutic intervention with significant positive effects on treatment outcomes and prognosis.
(pab)
Source: Senni M., Wachter R., Witte K. K. et al. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail 2020 Feb; 22 (2): 303–312, doi: 10.1002/ejhf.1670.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.