Novartis announced today results of the landmark PIONEER-HF trial showing that in-hospital initiation of Entresto tablets provided superior benefit compared to enalapril-a heart failure medication commonly used-in patients with HFrEF who had been stabilized following admission for an acute decompensation heart failure (ADHF) event. Results were presented as a late-breaker at the American Heart Association’s Scientific Sessions 2018 and published in The New England Journal of Medicine.
Patients on Entresto in PIONEER-HF had a 29% greater reduction in time-averaged N-terminal pro-B-type natriuretic peptide (NT-proBNP) at weeks 4 and 8 (the primary endpoint) compared to enalapril patients (95% CI: 0.63, 0.81; P<0.0001). Significant reductions in NT-proBNP were observed in Entresto patients as early as 1 week after treatment initiation. NT-proBNP is an established biomarker used to assess the severity and determine the prognosis of heart failure. Notably, the superior NT-proBNP reduction with Entresto was consistent across diverse HFrEF patient populations stabilized following admission for ADHF, including those newly diagnosed with HFrEF, those not receiving an ACEi/ARB treatment and African Americans.
In a pre-specified exploratory analysis of PIONEER-HF, Entresto also showed a significant 46% reduction in the risk of a composite of death, heart failure re-hospitalization (hospital stay >24 hours), requirement for left ventricular assist device (LVAD) insertion or listing for cardiac transplantation compared to enalapril over 8 weeks. This result was driven primarily by reductions in death and HF re-hospitalization among patients treated with Entresto. There were no new safety signals identified. Entresto is indicated to reduce the risk of CV death or HF hospitalization in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
“The results of this landmark study should help inform our basic approach to treating hospitalized patients with acute heart failure,” said Eric Velazquez, MD, Berliner Professor of Cardiology at Yale School of Medicine and PIONEER-HF principal study investigator. “With the PIONEER-HF trial results-once acute heart failure is diagnosed, patients are hemodynamically stabilized, and a low ejection fraction is confirmed-sacubitril/valsartan should be started promptly to reduce neurohormonal activation and reduce the risk of post-discharge heart failure hospitalization.”
“PIONEER-HF further confirmed the safety and benefit, as reflected in the reduction of an important biomarker, of in-hospital initiation of Entresto treatment in HFrEF patients stabilized following ADHF,” said Shreeram Aradhye, MD, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals. “Together with data from the PARADIGM-HF study, which demonstrated the superior benefit of Entresto compared to an ACEi on cardiovascular mortality and HF hospitalizations in ambulatory patients, there is now consistent evidence in the in and outpatient settings supporting the use of Entresto. Through the Entresto scientific program, we are reimagining the standard of care for HFrEF patients and the use of Entresto as foundation therapy.”
Patients with heart failure who need to be admitted to the hospital due to decompensation of their disease are at high short-term risk of death or being re-admitted to the hospital,. PIONEER-HF showed that Entresto can be initiated in the hospital in these patients safely, once they have been stabilized, with a tolerability profile comparable to enalapril. Rates of hypotension (low blood pressure), hyperkalemia (elevated levels of potassium) or renal (kidney) complications were similar and there was no greater risk of angioedema in patients treated with Entresto. There were no new safety signals identified, and the safety profile was comparable to that seen in PARADIGM-HF,. These results add to learnings from the TRANSITION study (an open label parallel group design), which explored the initiation of Entresto shortly after patients were stabilized following an acute heart failure episode, both in the hospital and out-patient settings,. Initial TRANSITION results were presented at the European Society of Cardiology Congress in August 2018. Additional bio-marker data from TRANSITION will be presented at AHA.