It’s an all-too-familiar—and frustrating—tableaux for cardiologists today. A patient comes into the office and announces he’s taken himself off his statin medicine. The reason: persistent muscle aches and pains. After weighing the evidence, the physician looks the high-risk patient in the eye and assures him continued use of the statin could reduce by 25 to 35 percent the risk of a future heart attack or stroke. It’s no use. The patient refuses to budge, and the physician glumly makes the entry in the patient’s record. “Part of it is just fatigue from patient after patient coming in and saying this medication is making me feel terrible,” acknowledges Michael Miedema, MD, a cardiologist at Minneapolis Heart Institute who has conducted research on statin intolerance. “Physicians feel it’s much easier to just stop the statin.”
One of the biggest mysteries around statins is how many patients are intolerant. “Statin intolerance”—generally defined as the inability to tolerate a dose of statin required to sufficiently reduce cardiovascular risk—has been linked primarily to muscle discomfort, though patients have also complained of fatigue, gastrointestinal issues, headaches, poor vision, cognitive dysfunction and much more. Studies suggest that statin intolerance afflicts between 15 to 20 percent of patients, though some cardiologists claim as many as half their patients report adverse events. Curiously, the recent GAUSS-3 (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3) randomized clinical trial to investigate an alternative treatment to statins found that 26.5 percent of patients who had failed three or more statins in phase A of the trial reported symptoms while taking a placebo, compared to 42.6 percent while taking atorvastatin (JAMA 2016;315:1580-90). “There are clearly people who have a real disorder, but there are also a lot of people who have perceived harms from their [statin] therapy,” says Steven Nissen, MD, chair of Cardiovascular Medicine at the Cleveland Clinic and lead investigator of GAUSS-3. “It’s called the ‘nocebo effect,’ and what makes it so vexing for doctors is trying to tell the difference.”
Not all patients who report a problem with their statin abandon it, of course, but the number is high enough to concern physicians. Researchers who analyzed information from a national Danish registry found that between 1995 and 2010, statin use among 675,000 individuals who were 40 years and older grew from 1 percent to 11 percent (Eur Heart J 2016;37:908-16). During that same period, the number of patients who discontinued their statins within the first six months tripled. Just as intriguing was the connection the study drew between that discontinuance and negative stories about statins in the press. Specifically, it found that patients were 9 percent more likely to stop their medicine when the news coverage was bad, and 8 percent less likely when the news coverage was positive. As for the all-important impact of their decisions on health outcomes, the Danish study found that patients halting their statins within the first six months had a 26 percent greater risk of heart attack and 18 percent greater risk of death than those who remained on the medication. In the U.S., a study of 79,240 Medicare patients who began moderate- or high-potency statins after suffering a myocardial infarction also raised red flags. It found that for statin-intolerant patients, the incidence of recurrent myocardial infarction was 41 percent vs. 32 percent for patients who adhered to their treatment (J Am Coll Cardiol 2016;67[13_S]:1838).
“Try & try again”
Given the stakes, do too many physicians prematurely throw in the towel when confronted with statin-intolerant patients? “I think so,” responds Salim Virani, MD, PhD, associate professor at Baylor College of Medicine and head of its lipid clinic. “Statins are a full class with lots of medications and options available, and physicians should be trying at least two or three medicines before labeling a patient statin intolerant. It could be life-saving for the patient.”
Indeed, there is growing clinical evidence that most patients who decide to end their statin regimens can be successfully rechallenged. One large retrospective study from Brigham and Women’s Hospital and Massachusetts General Hospital documented statin-related events in 17.4 percent of the patients it investigated. Of these, over 92 percent who