Combination of old and new drugs reduces CHF toll by twenty percent

By ACSH Staff — Sep 02, 2014
A new drug combination appears to reduce the toll of heart failure by almost one-fifth. Some caveats warrant attention, but for such a common, lethal condition, this therapy may change the standard of care if confirmed.

Heart skips a beatCongestive heart failure (CHF) is an all-too-common cause of clinical deterioration, diminished ability to perform normal activities, and hospitalization and death. CHF is the result of numerous types of cardiac conditions, including CAD/heart attacks and, especially, inadequately treated high blood pressure. There are other causes, more rarely, as well. CHF is the leading cause of hospitalization among the over-65 population and accounts for over $17 billion in healthcare expenditures.

The current study, known as PARADIGM-HF, was presented at the European Society of Cardiology meeting in Barcelona by Dr. Milton Packer, Professor and Chair for the Department of Clinical Sciences at University of Texas- Southwestern Medical Center; it was simultaneously published in last week s New England Journal of Medicine; the lead author is Dr. John J.V. McMurray of the British Heart Foundation and the University of Glasgow. The international (mostly European) authors randomized over 8,000 patients to receive either standard therapy plus an angiotensin converting enzyme (ACE)-inhibitor, enalapril, or standard therapy plus a combination of an angiotensin-receptor blocker, valsartan, and an investigational drug that inhibits a substance known to be elevated in CHF: neprilysin. The patients average age 64 all with substantially reduced heart function, were followed for an average of 27 months, when the study was stopped due to the clear evidence of benefit of the ARB-neprilysin inhibitor (the combination known as LCZ696, made by Novartis).

The study drug combo reduced the occurrences of death from all causes, death from heart failure, and hospitalizations from CHF by rates of between 18 percent and 25 percent. Further, adverse effects were uncommon in both groups, but were somewhat lower in the LCZ696 group. And the study group reported more improvement in activities of daily living than the enalapril group.

Mariell Jessup, M.D., of the Perelman School of Medicine at the University of Pennsylvania, in her editorial in the NEJM, said that neprilysin inhibition increases the inhibition of the renin-angiotensin-aldosterone system (RAAS) and thus reduces sympathetic drive. She concluded that PARADIGM-HF "may well represent a new threshold of hope for patients with heart failure."

Dr. Claude Yancy, while concerned about some caveats that need to be addressed before changing the standard of care for CHF only 5 percent of the subjects were black and only 20 percent were women nevertheless had this overall view, as told to MedPage Today: It's time to be bold and do something disruptive about heart failure; too many patients remain at risk for hospitalization, death and a poor quality of life. Let's take a patient centric view, now. My own patients and their families are eager to have more options and hesitant to accept unwarranted delays. We shouldn't be so intoxicated by our current success in treating heart failure that we take a nihilistic or circumspect view of these data. These data are sufficient. We should begin the conversation about implementation. For the still pending questions we have the research wherewithal to secure answers. Let's disrupt the norm. I vote for early adoption of these results." And Dr. Yancy was not involved in the study himself.