The use of statins for primary cardiovascular disease prevention in adults over age 75 is clouded in uncertainty. A recent study in the Journal of the American Geriatrics Society found that statins may significantly lower mortality risk in older adults. That only underscores the need for a large-scale, prospective, randomized clinical trial, researchers say.
Since the first statin received FDA approval in 1987, the drugs have become an important component of primary and secondary cardiovascular disease prevention.
“Numerous prospective, randomized clinical trials ... have demonstrated significant reductions in heart attack [and] cardiovascular disease death, and in at least one study, reduced risk of stroke,” says Michael W. Rich, MD, Director of the Cardiac Rapid Evaluation Unit at Barnes-Jewish Hospital and Professor of Medicine at Washington University School of Medicine in St. Louis. “There’s quite compelling evidence on the beneficial effects of statins, both in people who have known cardiovascular disease and in those who are at increased risk of cardiovascular disease by virtue of having other conditions, such as high blood pressure, diabetes, smoking and so forth, who take statins for primary prevention.”
Although the benefits of statins for primary prevention seem clear-cut, not much is known about their efficacy and safety in adults older than 75. The U.S. Preventive Services Task Force concluded in 2016 that there is insufficient evidence to make a recommendation for or against statin use for primary prevention in adults age 76 and older. The American Heart Association and American College of Cardiology reached similar conclusions in 2013.
“Few studies have included people over age 75, and no studies have included people over 82,” says Dr. Rich, who was not involved in the Journal of the American Geriatrics Society study but published an editorial discussing the research in the same journal.
This makes it difficult to determine if seniors may benefit from preventive statin use and to justify prescribing decisions.
“If you simply extrapolate data from younger people, you’d say, ‘Well, older people have more heart attacks and strokes, so presumably, we’re going to prevent more heart attacks and strokes in these people,’” says Ariela Orkaby, MD, MPH, Instructor of Medicine at Harvard Medical School, geriatrician at VA Boston Healthcare System, researcher at the New England Geriatric Research, Education, and Clinical Center, and lead author of the Journal of the American Geriatrics Society paper. “On the other hand, statins do carry a certain amount of risk, and we don’t really know what that impact is in older adults. Those risks involve primarily functional changes to the musculoskeletal system. It’s a hard trade-off to make when someone is older ... especially when there’s no evidence to guide therapy one way or the other.”
“The main take-home message is, ‘Yes, this paper adds to the existing literature, but it’s not definitive with respect to the benefits of statins in people beyond age 75 and, particularly, beyond the age of 80 years.’ We simply need more studies in the future to address this particular question.”
— Michael W. Rich, MD, Director of the Cardiac Rapid Evaluation Unit at Barnes-Jewish Hospital and Professor of Medicine at Washington University School of Medicine in St. Louis
A Quest for Clarity
Dr. Orkaby believed existing data might offer preliminary answers to the question of whether or not using statins for primary prevention helps lower the risk of mortality and cardiovascular events in older adults. She identified the Physicians’ Health Study, a two-phase trial conducted at Harvard Medical School over a period of more than two decades, as a potentially useful data set. As part of that trial, male physicians ages 40 to 84 with no personal history of cancer, stroke, heart attack or transient ischemic attack answered questions about their overall health, lifestyle, and medication and supplement use.
For their analysis, Dr. Orkaby and the research team included data from all participants age 70 and older who were involved in the study during and after 1999 — when questions about statin use were added to the questionnaire. Through propensity scoring and greedy matching, the researchers narrowed a pool that included 70,213 physicians into 1,130 similarly matched pairs of 2,260 men who were followed for an average of seven years. Each pair consisted of a man who took statins and a man who did not.
An Unresolved Dilemma
Statin use was associated with an 18 percent lower risk of all-cause mortality. Statins also slightly lowered the risk of cardiovascular events, but Dr. Orkaby notes that this reduction did not approach statistical significance. In addition, subgroup analyses revealed that adults older than 76 at the beginning of the study did not benefit from statins in the same way as individuals between ages 70 and 76.
The study also had limitations including a small sample size that featured only male participants.
Drs. Orkaby and Rich agree that more research is needed before drawing any definitive conclusions. Until more data become available, Dr. Orkaby recommends basing prescribing decisions on patients’ goals, functional status and life expectancy.
“There’s nothing magical that happens when patients age out of a guideline,” she says. “If somebody has been potentially benefiting from a statin, there’s probably a good reason to continue. On the other hand, if someone has a limited life expectancy, there really, most likely isn’t a role for a statin there.”