New Novartis study supports heart failure drug Entresto as foundational HFrEF therapy and in-hospital initiation in appropriate stabilised heart failure patients.
Novartis has announced the 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 stabilised 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.
Heart failure (HF) is a serious progressive disease with debilitating symptoms. HF patients are at risk of a sudden worsening of the disease that requires urgent care in hospital and it is the number one reason for hospitalisation in people over 65 years.
Heart failure drug Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS).
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. 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 heart failure drug Entresto was consistent across diverse HFrEF patient populations stabilised 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, heart failure drug Entresto also showed a significant 46% reduction in the risk of a composite of death, heart failure re-hospitalisation, 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-hospitalisation among patients treated with Entresto. There were no new safety signals identified. Entresto is indicated to reduce the risk of CV death or HF hospitalisation in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
Eric Velazquez, MD, Berliner Professor of Cardiology at Yale School of Medicine and PIONEER-HF principal study investigator said, “The results of this landmark study should help inform our basic approach to treating hospitalised patients with acute heart failure. With the PIONEER-HF trial results-once acute heart failure is diagnosed, patients are hemodynamically stabilised, 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 hospitalisation.”
Shreeram Aradhye, MD, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals said, “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 stabilised following ADHF. 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 re-imagining 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 stabilised, 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.