Two New Medications, the First in Years, Offer Exciting Possibilities for Mid-Stage Heart Failure Patients
Samer Najjar, MD, begins his presentations on heart failure with a graph showing the growth in heart failure in the U.S. The graph shoots upwards, the sort of skyward trajectory you want to see in the stock market but not in a disease rate chart.
The numbers are stunning: an estimated six million patients, up from 5.1 million just ten years ago. The American Heart Association projects that in 15 years, thanks to the rapid expansion of the older-than-65 population and the improved survival of patients who have heart attacks, the number with heart failure will pass 8 million. Heart failure accounts for several million doctor visits and more than a million hospitalizations annually. It is the single largest expenditure for Medicare, costing more than $38 billion a year.
So it is little wonder that Dr. Najjar and other advanced heart failure specialists are excited about the release of two new medications to treat one of the most common forms of heart failure.
“We look at this as a seismic change,” says Dr. Najjar, medical director of Advanced Heart Failure for MedStar Heart & Vascular Institute (MHVI) at MedStar Washington Hospital Center, “as this is the first time in over a decade that new medications have been approved by the FDA for treating heart failure.”
Standard therapy for these patients currently relies on a few medications that have been shown to improve survival for patients with heart failure and which have been used for the past several decades, including:
Angiotensin-converting enzyme (ACE) inhibitors, which have been the cornerstone of medical therapy for this condition for a quarter century. They work by having direct effects on the heart and blocking one of the hormones that causes blood vessels to contract, making it easier for the heart to pump.
Angiotensin II receptor blockers (ARBs), which are cousins of ACE-inhibitors that achieve similar effects by a slightly different mechanism.
Beta blockers, which slow the heart and probably help it conserve energy by blocking the action of the hormone epinephrine.
The first new drug, ivabradine, is sold as Corlanor® and, like beta blockers, it slows the heart rate but does not have any other known effect on the heart. Ivabradine was shown to lower the rate of hospital readmissions for patients with heart failure. It was approved last April and became available late in the fall of 2015.
The second drug, LCZ696 (marketed as EntrestoTM), takes an existing ARB (valsartan) and enhances it by combining it with a second medication, sacubitril. There is more excitement over Entresto, explains Dr. Najjar, because in a clinical trial with 8,400 participants published in The New England Journal of Medicine in 2014, “it was shown to reduce the risk of death and hospitalizations by 20 percent compared to an ACE-inhibitor. Its benefit was so strong that the clinical trial had to be stopped early. Entresto outperformed the ACE-inhibitor in almost all the clinical endpoints that were examined. You look at those statistics and just say ‘Wow.’”
Entresto is only effective for a specific heart failure diagnosis known as reduced ejection fraction, yet this includes about half of the heart failure population. While patients have not yet begun asking for the new drug, says heart failure specialist David Majure, MD, “I plan on transitioning most heart failure patients with reduced ejection fraction from the standard ACE-inhibitors and ARBs.”
One of the biggest barriers to these new drugs, says Dr. Najjar, is cost. “ACE inhibitors, ARBs and beta block- ers are cheap. These new drugs are not.” Medicare and private insurance companies are now actively working on sorting out their coverage plans.
As with all new drugs, there are also unanswered questions, notes Selma Mohammed, MD, PhD, MHVI heart failure specialist and researcher. “We want to better define the patient population that would benefit the most from these medications and better understand the long-term safety and side-effect profile,” she says. “There is also the possibility of looking at expanded indications for use of these medications to other patient populations.”
For example, she says, in the PARAGON-HF trial, a major multi-center trial is looking at Entresto. “This drug is being tested for treatment of heart failure with preserved ejection fraction,” she says, “for which no specific therapy now exists. If positive, this would represent the first effective therapy to treat heart failure with preserved ejection fraction.”