TRANSITION: Sacubitril/valsartan feasible as in-hospital HF treatment

MUNICH — Sacubitril/valsartan was safe and effective in patients stabilized after hospitalization for acute HF regardless of whether they received it in-hospital or after discharge, according to results of the TRANSITION study presented at the European Society of Cardiology Congress.

“Sacubitril/valsartan (Entresto, Novartis) has been primarily studied in chronic heart failure, so we wanted to study it in patients hospitalized for acute decompensated heart failure, where they have fluid overload, edema in their legs and dizziness from exercise,” Rolf Wachter, MD, professor of medicine and senior cardiology consultant at University Hospital Leipzig, Germany, told Cardiology Today. “If we have stabilized them, this is a great opportunity to improve their therapy so that they do not come back. However, the initiation of heart failure drugs after an acute heart failure event is not well studied, but it is something my institution and others do in daily practice.”

Wachter and colleagues randomly assigned 1,002 patients (mean age, 67 years; 75% men; mean left ventricular ejection fraction, 29%) hospitalized for acute decompensated HF with reduced EF to sacubitril/valsartan after being hemodynamically stabilized while still in the hospital or after discharge. Patients were also stratified by whether they were taking an ACE inhibitor, an angiotensin receptor blocker or neither before hospitalization. Of the cohort, 29% were newly diagnosed with HFrEF and 24% had not previously taken ACE inhibitors or angiotensin receptor blockers.

The primary endpoint was proportion of patients achieving the target dose of sacubitril/valsartan 200 mg twice daily at 10 weeks after randomization. Secondary endpoints included discontinuation due to drug-related adverse events and tolerability of different sacubitril/valsartan doses.

According to the researchers, the primary endpoint was achieved in 45% of the predischarge group and 50.4% of the postdischarge group (relative risk ratio [RRR] = 0.893; 95% CI, 0.783-1.019).

In addition, 62.5% of the predischarge group and 68% of the postdischarge group maintained a dose of 100 mg or 200 mg for at least 2 weeks leading to week 10 after randomization (RRR = 0.919; 95% CI, 0.839-1.008), whereas 86.4% of the predischarge group and 88.8% of the postdischarge group maintained any dose for at least 2 weeks leading to week 10 after randomization (RRR = 0.973; 95% CI, 0.929-1.02).

Study drug discontinuation occurred in 4.5% of the predischarge group and 3.5% of the postdischarge group (RRR = 1.287; 95% CI, 0.692-2.395), Wachter and colleagues found.

Rates of adverse events, serious adverse events and death did not significantly differ between the groups. Death rates were low and none were related to the study drug, according to the researchers.

“The most important finding is that it is as safe and efficacious to start sacubitril/valsartan in the hospital as in the outpatient setting, whether the patient is on a high dose or a medium dose of the drug,” Wachter told Cardiology Today. “You do not have to wait until discharge to start a patient on this therapy.” – by Erik Swain

Reference:

Wachter R, et al. Abstract P6531. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.

Disclosures: The study was funded by Novartis. Wachter reports he receives lecture fees from and serves on an advisory board for Novartis, his institution receives research grants from Novartis, and he has financial ties with Bayer, Boehringer Ingelheim, CVRx, Medtronic, Pfizer, Sanofi and Servier.