New Alternatives to Statins Add to a Quandary on Cholesterol
September 1, 2015 MVP Blog comments
Doctors have long faced a conundrum in prescribing statins to lower cholesterol and heart attack risk: The drugs are cheap and effective for most people, and large, rigorous clinical trials have found minimal side effects. But as many as 25 percent of those who try them complain of muscle pain. Others stop taking the drugs because, they say, they cause a hazy memory or sleep problems, among other side effects not documented in studies.
(NYTimes.com by Gina Kolata)
Now, with the approval on Thursday of the second in a powerful — and very expensive — new class of cholesterol-lowering drugs, the dilemma confronting doctors just got trickier. Should the people who need to lower their cholesterol, but say they cannot tolerate statins, be prescribed new drugs that cost more than $14,000 a year, potentially adding billions of dollars to the nation’s medical bill?
Doctors say their first responsibility is to patients, but it is hard for them or their patients to forget the price of drugs meant to be taken for a lifetime. The new drugs are approved for use by people with heart disease who cannot control their LDL, the dangerous cholesterol, by other means. Doctors say they try to work with patients to ensure that all who can safely take statins, many of which cost pennies a day, do so, but a substantial portion of patients insist the side effects are too severe.
At the Mayo Clinic here, Dr. Stephen L. Kopecky, who directs a program for statin-intolerant patients, says he is well aware that middle-age and older adults who typically need statins may blame the drugs for aches, pains and memory losses that have other causes. He also knows his patients peruse the Internet, which is replete with horror stories about the dangers of statins.
Yet he, like other doctors, also thinks some statin intolerance is real despite what clinical trials have shown. The problem: In the vast majority of cases, there is no objective test to tell real from imagined statin intolerance.
So what is he to do when patients insist they cannot take statins and he can find no other reason for the symptoms they attribute to the drugs?
“How can I not believe them?” he asks.
Experts say there is a pressing need for new cholesterol-lowering treatments. Coronary heart disease accounts for one in seven deaths in the United States or 375,000 a year. About one in four American adults takes statins, pills that block an enzyme needed to make LDL. The drugs are credited with helping save many lives, but even among those taking statins, only 20 percent to 26 percent of high-risk patients have LDL cholesterol levels below 70, a goal many doctors strive for. And that does not count the many high-risk patients who cannot or will not take statins. Estimates of their number range from one million to three million.
Before the advent of the new drugs, injected antibodies that block an enzyme involved in regulating levels of LDL, doctors had few options for statin-intolerant patients other than suggesting lower doses or different and less effective drugs. But now they will be able to offer the two new drugs — Praluent, made by Sanofi Regeneron and approved by the Food and Drug Administration last month, which costs $14,600 a year, and Repatha, made by Amgen and approved Thursday, at $14,100 a year.
The medicines can slash LDL to levels almost never before seen in adults. Although the drugs seem remarkably safe and free of side effects, large studies to test their safety and efficacy in preventing heart attacks, strokes and cardiovascular deaths are still underway. Results are not expected until 2017.
The looming bill for the new drugs, said Peter J. Neumann, a health economist at Tufts Medical Center in Boston, “raises questions about how much we are willing to pay for effective innovation in the face of uncertainty about long-term effects and questions of affordability.”
Insurers are also worried about higher drug costs pushing up premiums, economists say.
“We’ve reached a point where patients are increasingly facing five- and six-figure price tags for medications that they will take over the course of their lifetimes,” said Matthew Eyles, an executive vice president for America’s Health Insurance Plans, the national trade association for the insurance industry. “If this is the new normal to treat common and chronic conditions, how can any health system sustain that cost?”
Doctors with patients who maintain they are intolerant to statins say they are confronted with a clash between the art and the science of medicine.
Dr. Peter Libby, a doctor and researcher at Brigham and Women’s Hospital in Boston, said that in his role as a physician, “the patient is always right.” But, he added, “as a scientist, I find randomized, large-scale, double-blind studies more persuasive than anecdote.”
The statin trials, which involved tens of thousands of people, found no more muscle aches, the most common complaint, in patients who took statins than in those who took placebos.
The widely held belief that statins affect memory also has not been borne out in clinical trials, said Dr. Jane Armitage of the University of Oxford. She and her colleagues studied memory problems in 20,000 patients randomly assigned to take a statin or a placebo. “There was absolutely no difference,” she said.
In a separate study, they looked at mood and sleep patterns and again found statins had no effect. Another study, in Scotland, detailed cognitive testing of older people taking statins or a placebo, and also found no effect.
About one in 10,000 patients did have a dangerous complication, rhabdomyolysis, that involves the breakdown of muscles. It almost always occurred with the highest doses of statins and in patients who were also taking drugs that interact with statins, including a class called fibrates that interfere with the body’s elimination of statins. The condition can be detected with a blood test for a muscle enzyme, creatine kinase, that is released by damaged muscles and when it occurs patients must stop statins immediately.
There appears to be a small increase in diabetes in statin patients, first reported in a 17,000-patient, multiyear study known as Jupiter that studied rosuvastatin. The same problem was later verified with other statins.
In Jupiter, 3 percent of those taking rosuvastatin developed diabetes during the trial, compared with 2.4 percent of those taking a placebo. Those who got diabetes started out with elevated blood sugar levels or other major risk factors for diabetes. Statins appeared to slightly accelerate development of the disease — diabetes emerged about 5.4 weeks sooner, said Dr. Libby, a trial investigator. But, he added, those taking statins did not appear to get diabetes that would not have occurred anyway.
Nonetheless, Dr. Kopecky and others continue to question whether the reassuring clinical trial data truly reflects patients’ experience. One issue is the so-called run-in periods in which potential clinical trial participants are given experimental drugs before a trial begins to eliminate those who have problems with the drugs.
Most statin studies, though, enrolled people without this prior testing, randomly assigning them to take a statin or a placebo, Dr. Armitage said. In every case, there was no difference in side effects between those taking the statin and those taking a placebo.
Another criticism is that clinical trials excluded all but the healthiest people. Dr. Armitage disputed that idea. “Very often people were elderly,” she said. “Very often they had heart disease. Very often they had diabetes. It makes me very upset to hear that somehow the people in the trials are not real people.”
Five very real patients, all with a high risk of heart attacks, came one recent day to see Dr. Kopecky at the Mayo Clinic. They had tried statins and given up, complaining of side effects including muscle aches, digestive problems and, in one case, random thoughts. Dr. Kopecky suggested that three of them try the new drug Praluent.
Kathryn Peterson, 72, had a heart attack in March and needs to get her cholesterol level way down, but she said statins made her legs so weak she could not climb the steps in her two-story house. She tried another statin, and then another, and had the same reaction.
“Then I said, ‘That’s it. I am not going to try any more,’ ” she said.
Dr. Kopecky was troubled. Ms. Peterson has multiple sclerosis, breast cancer and osteoporosis. A heart attack five months ago raises her risk of another.
“We know your cholesterol is incredibly high,” Dr. Kopecky said. “We have to start you on something.”
He suggested Praluent, and she reluctantly agreed.
“I’m not jumping for joy,” Ms. Peterson said. “Five years from now, bad side effects might emerge or I might turn out to have an allergic reaction.”
“Being first is not something I wanted to do.”