The new drug, Amgen’s Repatha, is given as a shot once or twice a month and is part of a novel class of medicines that drop LDL to unprecedented levels.

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The first rigorous test of an expensive new drug that substantially lowers cholesterol levels found it significantly reduced the chance a high-risk patient would have a heart attack or stroke. These were men and women who had exhausted all other options.

Statins such as Lipitor and Crestor are cheap and lower LDL, or bad cholesterol, but some people can’t tolerate or get enough help from them. The new drug, Amgen’s Repatha, is given as a shot once or twice a month and is part of a novel class of medicines that drop LDL to unprecedented levels.

It costs more than $14,000 a year, and insurers have balked at paying without proof that it lowers heart risks, not just the cholesterol number. The new study gives that evidence, but the benefit is not as great as some doctors had hoped.

The results of the study, which cost about $1 billion and was paid for by Amgen, were published Friday in The New England Journal of Medicine and presented at the annual meeting of the American College of Cardiology in Washington, D.C.

Repatha is called a PCSK9 inhibitor and can make cholesterol tumble to levels rarely seen naturally in adults, or even in people taking cholesterol-lowering statins. The Amgen drug and a similar one, sold by Sanofi and Regeneron, were approved by the Food and Drug Administration (FDA) in 2015 with the hope — and expectation — that they would lower the risk of heart attacks and strokes, and not just reduce levels of LDL cholesterol.

That hope has now been realized for the Amgen drug.

“This is like the era of the statins coming in,” said Dr. Eugene Braunwald, a cardiologist at Harvard Medical School who was founding chairman of the research group that conducted the study, but was not an investigator on it. Like statins, which were introduced in the 1980s, the new class of drugs has the potential to improve the health and longevity of millions of Americans with heart disease, the nation’s leading killer, accounting for 1 in 4 deaths.

“It’s a new ballgame,” he said.

But Dr. Donald Lloyd-Jones, preventive medicine chief at Northwestern University and an American Heart Association spokesman, called the results modest and “not quite what we hoped or expected.”

Dr. Mark Hlatky, a Stanford University cardiologist and cost-effectiveness researcher, said, “People were hoping for a breakthrough, a lot bigger result than 20 percent.”

Cost will be an issue. Statins are available as cheap generics. The new drugs have a list price of $14,523 a year. “The next big challenge is financial: how to pay for it,” said Dr. David Maron, director of preventive cardiology at Stanford, who also was not involved in the study.

Insurance companies have been reluctant to pay for the drug without evidence it protected high-risk patients from heart attacks and strokes. Kristine Grow, a spokeswoman for the insurers’ organization America’s Health Insurance Plans, said insurers would consider the new data.

Investors greeted the trial results with initial disappointment Friday and appeared to assume that insurers would continue to restrict access to the drug, in part because it did not show a benefit in overall death rates from cardiovascular causes.

Ronny Gal, an analyst for Sanford Bernstein, estimated that insurers would have to pay nearly $1 million to prevent one event in a patient and said in a note to investors that while use of the drug would expand, it would do so gradually. “The tension between patient benefit and the very high price charged for it will remain, in our view, the dominant issue,” he wrote.

Dr. Harlan Krumholz, a Yale cardiologist, agreed that given the expense of the drug, the results raise questions about what it is worth and who should get it. But he called the study “a solid outcomes trial” and said “we should celebrate” that it showed the drug is capable of reducing risk.

The problem, he said, was that expectations were running so high. “There was a lot of hubris about how pushing LDL down to 30 would eliminate heart disease,” he said. It did not. About 10 percent of patients taking the drug had a heart attack or stroke, or died of heart disease during the trial.

The study involved 27,564 men and women. About 80 percent had already had a heart attack, and the rest had already had a stroke or had pain in their legs and feet from narrowed arteries. They were taking optimal doses of inexpensive, cholesterol-lowering statins, which gave them an average LDL of 92, well within the range — an LDL of less than 100 — that has been advised for high-risk patients.

All continued with their statins, but half were assigned to inject themselves with Repatha, also known as evolocumab, and the rest were assigned a placebo. Those taking the new drug reached an average LDL of 30. A quarter of participants got to an LDL of 19 or lower.

Amgen estimates 11 million Americans are eligible to take the drug. They include people like those in the study and people who have a genetic condition, familial hypercholesterolemia, that results in intractably high LDL levels and a grave risk of a heart attack.

Amgen maintains that its drug is worth the price and that by preventing heart attacks and strokes, it will also prevent the costs associated with treating patients with worsening conditions. But the drug would need to be taken for life, and the bill for its widespread use could potentially be huge.

For cardiologists, the study was a crucial test of a long-held hypothesis: the lower the level of cholesterol in the blood, the better.

The results support that hypothesis. There seemed to be no floor to the benefits of cholesterol lowering, at least down to the stunningly low levels achieved in the study. The lower the LDL, the lower the risk, with no leveling off of the linear relationship.

Maron said the results were “incredibly important,” adding, “The future looks brighter for patients with established coronary disease.”

But Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, tempered her enthusiasm, saying she would like to see what happens to the death rates over a longer period.

Redberg also worried about the potential for bias because Amgen paid for the study, helped design it, collected the data and helped write the paper. The data analysis was done independently by a team of academic researchers, led by Dr. Marc S. Sabatine, chairman of a cardiovascular research group called TIMI at Brigham and Women’s Hospital, a teaching hospital for Harvard Medical School.

Participants in the study who used Amgen’s drug for 2.2 years were 20 percent less likely to die from heart disease, have a heart attack or have a stroke (816 patients taking the drug had one of those outcomes, compared with 1,013 taking the placebo).

There was a 15 percent reduction in the combined risk of having a heart attack or stroke or dying from cardiovascular disease, being hospitalized for worsening chest pain, or having a stent inserted to open a blocked artery (1,344 Repatha patients versus 1,563 placebo patients).

“Reducing the risk of a heart attack or stroke by 20 percent is a pretty big reduction,” Sabatine said. He and others predicted that the risk would be reduced further as time went on, as it does in patients taking statins. He noted the effect was already emerging, with a 25 percent reduction in the second year.

The only side effect seen during the study was a small incidence of redness or itching at the injection site, with 2.1 percent of those taking the Amgen drug reporting such effects, compared with 1.6 percent of those taking the placebo injections. But patients in general did not stop using the drug for that reason.

Robert Johnson, 51, of Glen Mills, Pennsylvania, had a father who died of a heart attack at age 42. He has familial hypercholesterolemia, and his LDL in 2011 was 377. He’s taking the Amgen drug and a statin. Now his LDL is about 80.

“I feel much safer, much better,” he said. “I always felt there was a ticking time bomb in my heart.”

For patients like Susan Goodreds, 74, whose insurance copay for Repatha is $356 a month, it’s not an easy choice.

“It’s an expensive, expensive drug,” the Florida woman said. “You have to make some real decisions about whether to stay on it.”