New drug improves treatment of heart failure

In a huge international study, an experimental drug for heart failure worked significantly better than the current backbone of treatment, paving the way for the biggest therapeutic advance in decades.

Novartis’ twice-a-day pill, still known by its code name LCZ696, reduced deaths, hospitalizations, and disabling symptoms of heart failure. It also had fewer serious side effects than the standard therapy, a blood-pressure-lowering medication called enalapril.

“We designed this study to try to change the cornerstone of treatment — to replace enalapril,” said the study’s lead co-author, Milton Packer, a cardiologist and heart failure researcher at University of Texas Southwestern Medical Center. “The results are not only compelling, but exceeded our expectations.”

In an editorial accompanying the study, published online Saturday in the New England Journal of Medicine, University of Pennsylvania cardiologist Mariell Jessup, wrote that the novel therapy may “represent a new threshold of hope for patients with heart failure.”

Heart failure, the only cardiovascular disease on the rise, affects 5 million people in the U.S.

A progressive disorder, it begins when heart cells are injured by a heart attack, infection, chemotherapy, or other causes. Healthy cells try to compensate by overworking and enlarging, while the body retains water and increases blood pressure in a futile effort to improve blood flow.

Until the 1980s, the standard treatments — digoxin, which strengthens heart contractions, and diuretics, which increase urine output — did nothing to reduce mortality, and little to relieve the symptoms of breathlessness, fatigue and swelling.

Then came enalapril, approved in 1985, the first in a class of drugs called ACE inhibitors. These compounds, which lower blood pressure by widening the blood vessels, improved symptoms and survival. Further progress was made by combining ACE inhibitors with drugs that block adrenaline, as well as more sophisticated diuretics.

Even with all this and more — heart failure patients typically take four to eight drugs — about 50 percent die within five years.

The latest advance involves blocking an enzyme, neprilysin, that plays a key role in the complex process of blood vessel constriction, fluid retention, and heart enlargement that makes the heart gradually fail.

“This is a new pathway. That’s what’s really exciting,” Jessup said, adding that other pharmaceutical companies are developing their own anti-neprilysin compounds.

Novartis’ new drug combines its neprilysin inhibitor with valsartan, a blood pressure-lowering drug that works somewhat differently from enalapril.

The pivotal study, begun in 2009, enrolled 8,400 patients with mild to moderately severe heart failure at more than 1,000 centers around the world, making it the largest clinical trial in heart failure ever undertaken. The patients were randomly assigned to take LCZ696 or enalapril, plus other medications that were part of their prescribed regimen.

The trial was stopped early, after following patients for a median of 27 months, because the new drug met criteria for “overwhelming benefit.”

Of 4,187 patients on the new drug, 914 died from cardiovascular causes or were hospitalized for worsening heart failure — 21.8 percent of the group. That compared with 1,117 deaths and hospitalizations (26.5 percent) among 4,212 people taking enalapril.

The Novartis drug was also better tolerated. Slightly less than 11 percent quit it because of side effects such as dangerously low blood pressure or worsening kidney function, compared with about 12 percent for enalapril.

On a questionnaire, patients taking LCZ696 reported more improvement in heart failure symptoms and physical limitations than the comparison group.

Novartis will now ask the U.S. Food and Drug Administration to approve the drug based on the results.

More in Local News

Senate Democrats propose property tax cut with surge in revenue

The latest revenue forecast predicted $1.3 billion more in the next three years than anticipated.

Water to be shut down for up to 2 days for about 100 homes

The city of Everett plans to disable one of four pipelines next week while crews work on the system.

Northshore School District bond for new elementary now passing

As of Tuesday, the $275 million proposal was comfortably above the 60 percent supermajority.

“Compromised by deterioration,” Everett apartments condemned

The city says the conditions at Broadway Station Apartments were unsafe for tenants.

Clear, cold weather could give way midweek to chance of snow

A chance of lowland snow looms for Snohomish County by… Continue reading

Load up: Cheesecake Factory plans Lynnwood location

The chain restaurant is listed as a tenant in new development at Alderwood mall.

Everett appeals court’s ban on dress code for bikini baristas

The baristas say they seek to protect their civil rights. The case is on hold pending the appeal.

Lake Stevens girl wants to make sure her peers are well fed

Anneliese Ballou, 9, was named the first student ambassador by the Hungry Hearts Foundation.

Front Porch

EVENTS Snow goose festival coming up The Port Susan Snow Goose and… Continue reading

Most Read