The first rigorous test of an expensive new drug that radically lowers cholesterol levels found that it significantly reduced the chance that a high-risk patient would have a heart attack or stroke. These were men and women who had exhausted all other options.
The results of the study, which cost about $1 billion and was paid for by Amgen, maker of the drug, were published on Friday in The New England Journal of Medicine and presented at the annual meeting of the American College of Cardiology.
The drug, Repatha, is called a PCSK9 inhibitor and can make cholesterol tumble to levels almost never 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 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, the dangerous kind.
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 not involved in the study. 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 one in four deaths.
“It’s a new ballgame,” he said.
But 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.
The study involved 27,564 men and women. About 80 percent had already had a heart attack, and the rest had 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 under 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 that about 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.
Dr. 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 over a longer period of time.
Dr. 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.
