Not long after guidelines shifted to considering statin therapy as early as age 30, new research from France suggests there may be no harm in stopping the cholesterol-lowering drugs at age 75 in people with no history of cardiovascular disease. The lessons, however, may not translate elsewhere.
The “non-inferiority” study, published Tuesday in the Lancet Healthy Longevity, does not advise doctors to tear up statin prescriptions for older people. Nor does it conclude that going off statin therapy is better than staying on. It does say patients should talk to their doctors to see if they’d be no worse off for dropping the daily pills.
Invoking patient choice, the authors highlight the lack of scientific literature on older people, noting what research does exist has found the link between cholesterol and cardiovascular events weakens with age. They believe their own study needs to be repeated for a longer period of time and extended to populations at higher cardiovascular risk or otherwise not as healthy as their participants.
“For the majority of American patients over the age of 75, this trial will not change anything,” Romit Bhattacharya, a general and preventive cardiologist from the Mass General Brigham Heart and Vascular Institute, told STAT in an interview. He was not involved in the research. “It does give us a little bit of permission and greater flexibility and choice for our individuals who maybe have a short time horizon to live and who are already quite healthy and engaged in care.”
In the randomized trial, 1,160 patients were enrolled in general practitioners’ offices across France, which has universal health care and the lowest burden of cardiovascular mortality among high-income countries as well as higher longevity than the U.S. With an average age of 80, the participants had been prescribed statins at least one year before as a preventive measure to stave off atherosclerotic cardiovascular disease. Most had been on statins for at least five years. High LDL, or “bad,” cholesterol is the trigger for a conversation about avoiding the buildup of fatty plaque inside the arteries.
Split into two groups, they were followed for three years. One difference popped up early: After three months, LDL cholesterol jumped 50% higher (climbing from 115 to 171 mg/dL), while the group staying on statins saw no change.
At the study’s end, differences in outcomes were small. After three years, 7.2% (35 out of 484) people in the statin discontinuation group had died, compared with 7.9% (48 out of 604) in the continuation group. Those death rates are half the national average of 15% in France.
There was no significant difference in major cardiovascular events, including heart attacks and strokes, between those who stopped statins and those who continued. Quality of life measures, both physical (Can you climb stairs? Are you in pain?) and mental (Are you sad? Is your social life limited?), stayed the same for both groups over the three years.
“This is a specific population, I think that’s the main point, and it has to be confirmed in other populations,” study co-author Fabrice Bonnet, professor of internal medicine and head of internal medicine and infectious disease at Bordeaux University Hospital, told STAT.
Not surprised by the results of this study, the authors were a little disappointed that there was no benefit in terms of quality of life of stopping statins, Bonnet said. One explanation could be that patients who were bothered by the drugs had already stopped taking them. For the trial, randomly assigning participants to stay on or off them was intended to level that playing field.
That could explain why the new study’s results fly in the face of other, larger — but not randomized — trials from 2021 conducted in Denmark and Italy. Those cohort studies showed about a 30% higher risk for both fatal and nonfatal cardiovascular outcomes after statins were discontinued in people 65 and older in the Italy study and 75 and older in the Denmark one.
The Lancet authors say those earlier trials left out an important component: why people were no longer taking statins. The researchers compared two cohorts, as opposed to looking at similar groups randomly assigned to take or not take statins. That approach raises the risk of bias because people might have started or stopped taking statins for many reasons, including complications or risks from other conditions, Bonnet and his co-authors wrote.
Statins have acquired a bad reputation for side effects, even though years of research have failed to connect the drugs to most complaints. They do have two well-known side effects: muscle pain in 1% of people, and a small increase in blood sugar levels, which could nudge people on the cusp into type 2 diabetes. But a recent study looking at the 66 side effects described in the pills’ package insert said 62 don’t stand up to scrutiny.
Their benefits have been consistent, lowering the risk of heart attacks and stroke by 25% since they were introduced in 1987.
Interest in deprescribing has grown along with the wider phenomenon of polypharmacy, the term for taking multiple medications, in these cases to manage blood pressure, heart failure, obesity, or diabetes in addition to cholesterol. Doctors are encouraged to review medications patients have taken for a long time, which much of the time means older patients.
“The decision about statins should be an individualized decision, based on the patient’s expected longevity, comorbidities, understanding of potential risks, and personal preferences,” Donald Lloyd-Jones, former president of the American Heart Association and current professor of medicine, preventive medicine, and epidemiology at Boston University Chobanian & Avedisian School of Medicine, told STAT via email, citing recent guidelines jointly issued by AHA and other groups. Not involved in the study, he is also director of the Framingham Center for Population and Prevention Science and principal investigator of the Framingham Heart Study.
Age matters, Bonnet said, when considering risk factors like diabetes, hypertension, social determinants of health, and smoking.
“If a patient is worried about the number of medications he’s been taking for years when he reaches 70 or 80 years old and the question of statins emerges, then you can be reassuring on stopping statins,” Bonnet said. “Cholesterol is no longer a high risk for elderly people. At 50 years old, it is, but at 75, it is no longer, when you have diabetes and hypertension.”
Care should be taken in those evaluations, Shefa Arya Nezhad, Parvaneh Rastgou, and Michael Nanna of the Yale School of Medicine wrote in a commentary appearing with the Lancet Healthy Longevity article.
“Deprescribing should not be confused with therapeutic nihilism,” they said. “The goal is not simply to reduce the number of medications, but to ensure that treatment remains aligned with an individual’s expected benefit, overall health status, and personal goals.”
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