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.

Talk to us

> Give us your news tips.

> Send us a letter to the editor.

> More Herald contact information.

More in Local News

Trader Joe’s customers walk in and out of the store on Monday, Nov. 20, 2023 in Everett, Washington. (Olivia Vanni / The Herald)
New Trader Joe’s opens this week at Everett Mall

It’s a short move from a longtime location, essentially across the street, where parking was often an adventure.

Ian Bramel-Allen enters a guilty plea to second-degree murder during a plea and sentencing hearing on Wednesday, March 6, 2024, at Snohomish County Superior Court in Everett, Washington. (Ryan Berry / The Herald)
‘Deep remorse’: Man gets 17 years for friend’s fatal stabbing in Edmonds

Ian Bramel-Allen, 44, pleaded guilty Wednesday to second-degree murder for killing Bret Northcutt last year at a WinCo.

Firefighters respond to a small RV and a motorhome fire on Tuesday afternoon in Marysville. (Provided by Snohomish County Fire Distrct 22)
1 injured after RV fire, explosion near Marysville

The cause of the fire in the 11600 block of 81st Avenue NE had not been determined, fire officials said.

Ashton Dedmon appears in court during his sentencing hearing on Tuesday, March 5, 2024, at Snohomish County Superior Court in Everett, Washington. (Ryan Berry / The Herald)
Everett Navy sailor sentenced to 90 days for fatal hit and run

Ashton Dedmon crashed into Joshua Kollman and drove away. Dedmon, a petty officer on the USS Kidd, reported he had a panic attack.

A kindergarten student works on a computer at Emerson Elementary School on Wednesday, Feb. 28, 2024, in Everett, Washington. (Ryan Berry / The Herald)
‘¡Una erupción!’: Dual language programs expanding to 10 local schools

A new bill aims to support 10 new programs each year statewide. In Snohomish County, most follow a 90-10 model of Spanish and English.

Cassie Franklin, Mayor of Everett, delivers the annual state of the city address Thursday morning in the Edward D. Hansen Conference Center in Everett, Washington on March 31, 2022.  (Kevin Clark / The Herald)
At Everett mayor’s keynote speech: $35 entry, Boeing sponsorship

The city won’t make any money from the event, city spokesperson Simone Tarver said. Still, it’s part of a trend making open government advocates wary.

Logo for news use featuring the Tulalip Indian Reservation in Snohomish County, Washington. 220118
Woman drives off cliff, dies on Tulalip Reservation

The woman fell 70 to 80 feet after driving off Priest Point Drive NW on Sunday afternoon.

Everett
Boy, 4, survives fall from Everett fourth-story apartment window

The child was being treated at Seattle Children’s. The city has a limited supply of window stops for low-income residents.

People head out to the water at low tide during an unseasonably warm day on Saturday, March 16, 2024, at Lighthouse Park in Mukilteo, Washington. (Ryan Berry / The Herald)
Everett shatters record high temperature by 11 degrees

On Saturday, it hit 73 degrees, breaking the previous record of 62 set in 2007.

Snohomish County Fire District #4 and Snohomish Regional Fire & Rescue respond to a motor vehicle collision for a car and pole. The driver was pronounced dead at the scene, near Triangle Bait & Tackle in Snohomish. (Snohomish County Sheriff’s Office)
Police: Troopers tried to stop driver before deadly crash in Snohomish

The man, 31, was driving at “a high rate of speed” when he crashed into a traffic light pole and died, investigators said.

Alan Dean, who is accused of the 1993 strangulation murder of 15-year-old Bothell girl Melissa Lee, appears in court during opening statements of his trial on Monday, March 18, 2024, at Snohomish County Superior Court in Everett, Washington. (Ryan Berry / The Herald)
31 years later, trial opens in Bothell teen’s brutal killing

In April 1993, Melissa Lee’s body was found below Edgewater Creek Bridge. It would take 27 years to arrest Alan Dean in her death.

Logo for news use featuring the municipality of Snohomish in Snohomish County, Washington. 220118
Man dies after crashing into pole in Snohomish

Just before 1 a.m., the driver crashed into a traffic light pole at the intersection of 2nd Street and Maple Avenue.

Support local journalism

If you value local news, make a gift now to support the trusted journalism you get in The Daily Herald. Donations processed in this system are not tax deductible.