Both old and new drugs may offer fresh ways to fight heart disease
Novel drugs — some old, some new — may offer patients fresh ways to reduce their heart risks beyond the usual medicines that lower cholesterol and blood pressure.
One new study found that heart attack survivors benefited from a medicine long used to treat gout. Several experimental drugs also showed early promise for interfering with heart-harmful genes while leaving the genes themselves intact.
The research was featured at an American Heart Assn. conference that wrapped up Monday in Philadelphia.
“There’s a lot of excitement” about the new gene-targeting medicines, especially because they seem to last so long, said Karol Watson, a cardiologist and researcher at UCLA.
Scientists have been exploring gene therapy to attack the root cause of many diseases by altering a patient’s DNA. The new drugs essentially accomplish the same thing without tampering with genes, said Daniel Rader, a doctor who studies the genetics of cardiovascular disease at the University of Pennsylvania’s Perelman School of Medicine. (Rader has consulted for some makers of these drugs.)
The medicines work by silencing or blocking messages that genes give to cells to make proteins that can do harm. For example, they can hinder cells’ ability to allow cholesterol to accumulate. The first few of these “RNA-interference” drugs recently were approved for other conditions, and research is also targeting heart disease.
Furthest along is inclisiran. It was tested in 1,561 people with heart disease from clogged arteries who still had high LDL, the bad form of cholesterol, despite taking standard drugs. Patients were given a shot of inclisiran or a placebo when they joined the study, again three months later and then every six months.
The drug lowered LDL by 56% without serious side effects. More testing will show whether that leads to fewer heart attacks and other problems. Inclisiran’s maker, the Medicines Co., plans to seek federal approval for the drug later this year.
Two other RNA-interference drugs aim at a different target — triglycerides, another fat in the blood that’s elevated in one quarter of Americans. Treatments include very low-fat diets, weight loss, fish oil and drugs, but doctors say more and better therapies are needed.
Both RNA-interference drugs were tested at various doses in 40 people. A single shot lowered triglycerides by 30%, to 67%, and the benefit lasted for at least four months.
The studies were only intended to see if they were safe; trials of their effectiveness will come next. Arrowhead Pharmaceuticals is developing both drugs.
Other research found new benefits from older drugs.
AstraZeneca’s Farxiga, originally developed to treat diabetes, also lowered the risk of heart problems in heart failure patients who did not have diabetes. Among 2,605 such patients treated for 18 months, about 9% of those on Farxiga had worsening heart failure or heart-related death versus nearly 13% of those not given the drug. That worked out to a 27% lower risk, without producing additional serious side effects.
Surprising benefits also were seen in a Canadian study of a decades-old gout drug. The anti-inflammatory drug colchicine — sold as Colcrys, Mitigare and in generic form — was tested in 4,745 people who recently had a heart attack.
After about two years, colchicine users had a 23% lower risk of suffering a new heart attack, heart-related death, stroke, cardiac arrest or urgent need for an artery-opening procedure compared with a group given dummy pills, according to results published in the New England Journal of Medicine.
The benefit came mostly from preventing strokes and artery-opening procedures. Some heart doctors said they would rather have seen more difference in heart attacks and deaths.
Colchicine is being tested in several other studies, and more evidence is needed before using it routinely to lower heart risks, L. Kristin Newby, a Duke University cardiologist, wrote in a commentary published with the study in the New England Journal of Medicine.
Donald Lloyd-Jones, a Northwestern University cardiologist and program chief for the heart conference, was more supportive.
“When you have a safe drug that’s easily available,” he said, “it’s going to be hard to hold this one back.”