Sacubitril/valsartan safe to initiate after acute HF episode
The recent TRANSITION study shows that sacubitril/valsartan can be initiated early and safely in a wide range of heart failure (HF) patients with reduced ejection fraction (HFrEF) who have been stabilized after hospitalization due to an acute HF episode. Patients involved in the study included those with no prior experience of sacubitril/valsartan or conventional HF therapies, as well as those with prior experience of conventional HF therapies.
About half of all HF patients have reduced ejection fraction and optimizing treatment for these patients according to European Society of Cardiology guidelines is critical to reduce the likelihood of another acute episode or dying. However, there is often hesitancy to initiate a new treatment after a hospitalization as these patients are considered ‘vulnerable’ and unable to tolerate changes in their medication.
The study investigator Professor Rolf Wachter (University Hospital Leipzig, Germany) said, “In the weeks following an episode of acute HF, patients are very vulnerable and face a high risk of re-hospitalization and death. The PARADIGM-HF study* showed that sacubitril/valsartan reduces HF-related hospitalizations, re-hospitalization and death. TRANSITION shows that sacubitril/valsartan can be initiated early and safely in patients shortly after an acute HF episode, providing physicians with added confidence to optimize their care with innovative medicines in HF treatment.”
In TRANSITION, the safety and tolerability of sacubitril/valsartan were assessed in HFrEF patients after they have been stabilized following an acute HF episode. Patients were randomized to initiate sacubitril/valsartan therapy either in the hospital (pre-discharge) or shortly after leaving the hospital (post-discharge). At 10 weeks, more than 86% of patients were receiving sacubitril/valsartan for 2 weeks or longer without interruption and about half of patients in the study achieved the primary endpoint which was a target dose of 200 mg of sacubitril/valsartan twice daily within 10 weeks in both groups. The number of patients who met the primary and secondary endpoints was similar across both treatment arms. The incidence of adverse events and discontinuations of sacubitril/valsartan due to adverse events was also similar in both the in-hospital and the out-patient setting.
The TRANSITION study
TRANSITION (NCT02661217) is a randomized, phase IV, multicentre, open-label, parallel-group study, which assessed the safety and tolerability of sacubitril/valsartan (Entresto®) in 1002 HFrEF patients, from 156 hospitals worldwide, after stabilization following hospitalization for acute HF, when treatment was started in hospital (pre-discharge) or shortly after leaving hospital (post-discharge). Patients were grouped based on their pre-admission treatment status: those who were receiving an ACE inhibitor (ACEI) or an angiotensin receptor blocker (ARB), or those with no prior experience with an ACEI/ARB. Following screening and randomization, the study comprised a 10-week treatment period followed by a 16-week follow-up phase. The primary and secondary endpoints were the number of patients achieving the target dose of sacubitril/valsartan of 200 mg twice daily at week 10 (regardless of previous dose interruption or down-titration), and number of patients maintaining 100 mg or 200 mg bid for at least two weeks leading to week 10 after randomization, respectively.
* The landmark PARADIGM-HF study showed that sacubitril/valsartan was superior to enalapril in reducing CV mortality, HF hospitalization and 30-day hospital readmission in heart failure patients with reduced ejection fraction. (McMurray JJV, et al. N Engl J Med 2014;371:993-1004; Desai, AS, et al. JACC 2016;68(3):241-248).
This study shows that sacubitril/valsartan can be safely initiated shortly after an acute heart failure episode, both in the hospital and in an out-patient setting and in a wide range of stabilized patients.
In Europe, sacubitril/valsartan (Entresto) is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction. In the United States, it is indicated for the treatment of heart failure (New York Heart Association class II-IV) in patients with systolic dysfunction. Approved indications may vary depending upon the individual country. Please refer to your local SPC.
Wachter R. et al., Initiation of sacubitril/valsartan in hospitalized patients with heart failure with reduced ejection fraction after hemodynamic stabilization: Primary results of the TRANSITION study. Data presented at: ESC 2018, Aug 25-29; Munich, Germany.