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Novel Heart Failure Drug Combo Cuts CV Mortality More Than Enalapril — Physician’s First Watch

Medical News |
August 30, 2014

Novel Heart Failure Drug Combo Cuts CV Mortality More Than Enalapril

By Joe Elia

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM

LCZ696, an experimental compound that inhibits both angiotensin and neprilysin, "may well represent a new threshold" in treating heart failure, according to an editorialist in the New England Journal of Medicine. Neprilysin is an endopeptidase that degrades certain endogenous vasoactive peptides; its inhibition increases levels of these peptides, offsetting the neurohormonal overactivation seen in heart failure.

In the phase III PARADIGM-HF trial, also published in NEJM, some 8400 patients with class II to IV disease and ejection fractions of 40% or lower were randomized to LCZ696 or the ACE inhibitor enalapril. LCZ696 comprises the angiotensin-receptor blocker valsartan and the neprilysin inhibitor sacubitril.

After a median follow-up of roughly 2 years, the composite primary outcome of cardiovascular mortality or first hospitalization for heart failure was reduced by 20% with LCZ696 relative to enalapril. In particular, cardiovascular death occurred in 13.3% of the LCZ696 group versus 16.5% of the enalapril group (hazard ratio, 0.80).

The number of patients needed to be treated with LCZ696 to prevent one cardiovascular death was 32.

In NEJM Journal Watch Cardiology, Harlan Krumholz writes: "This trial provides welcome news for patients with chronic heart failure and reduced systolic function. On first look, these are stunning results, although whether they are generalizable to more-typical older patients with HF (compared with an average age of 64 in this cohort) remains to be seen. It would be nice to see validation in another trial before this drug becomes a standard of care — but many people will consider this evidence to be more than adequate to support its use."

PARADIGM-HF was conducted with the participation of LCZ696's manufacturer.

Reader Comments (6)

Héctor Tacchi Physician, Cardiology, particular office

Me parece una droga interesante y este informe es muy importante para comenzar con una terapia distinta en la IC crónica después de varios años sin verdaderos cambios. Tal vez sería oportuno definir si los péptidos natriuréticos están verdaderamente aumentados en la IC, porque la literatura no afirma categóricamente ese concepto. Para ello me gustaría conocer si en este estudio se utilizo el método tradicional para evaluar los niveles de PN plasmáticos (Bi0site) o se utilizó el método espectrometría de masa cuantitativo, porque como se ha escrito en algunos trabajos recientes, este método evalúa los PN activos(maduros) y no algunos productos de degradación e incluso inactivos como parece evaluarse con el método tradicional. Además, me gustaría conocer si han encontrado diferencias en este tema específico entre la IC isquémica (60%) y la No isquémica, el nivel de PN, la respuesta al tratamiento , etc. Esto ayudaría a aclarar algo que está escrito en los últimos años referente a que en realidad los péptidos nariuréticos se elevan por la hipoxia miocárdica y no tanto por el stress aumentado de la pared ventricular

Riaan Joubert Physician, Surgery, General, Randfontein South Africa

Why not an enalapril+sacubitril arm as well? It seems like an effort to put valsartan in a better light.

Suboohi Jafar Resident, Other, Safdarjung Hospital, New Delhi

Lets hope for d best results with d drug..if it will be beneficial..then it's a great achievement in d medical field.

Dr. Adekunle Adeniji Randle General Hospital, Surulere, Lagos, Nigeria.

This drug holds the potential to radically change the standard of care in heart failure patients s

H ROBERT SILVESTEIN Physician, Cardiology, Preventive Medicine Center

I find the choice of enalapril as the ACE Inhibitor comparator odd in order to determine the effectiveness of the new angiotensin-neprilysin blocker LCZ696. If benazepril or ramipril or lisinopril had been the ACE I tested, I suspect the improvement might have been less than the "20%" reported in the study. HRS, MD, FACC

Profesor Izzi Blitz Physician, Internal Medicine, Universidad del Zulia School of Medicine..

Enalapr4il Was The First Generation Fron The ECAS...now you Kmow that we are in the Trird Generation So Enalapril is OUT....Thamks

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