Statin Discontinuation Common, but Patients Can Be Rechallenged to Try Again

April 01, 2013

BOSTON, MA — Nearly one in five patients treated with a statin in a routine-care setting had a statin-related adverse event documented, the most common of which was myalgia or myopathy, and more than half of these patients stopped taking the medication at least temporarily, according to the results of a new analysis[1].

Despite these results, investigators also showed that more than half of patients who stopped taking the statin because of a statin-related event were successfully restarted with a statin, including some who took the same drug, over the following 12 months. "It is worth trying again," senior researcherDr Alexander Turchin (Brigham and Women's Hospital, Boston, MA) told heartwire , "given how important and lifesaving the statin drugs are. We don't have a lot of drugs that have been shown to reduce all-cause mortality, but statins are one of the few classes of drugs that do."

The results of the study are published April 1, 2013 in the Annals of Internal Medicine.

More Than 130 000 Treated With Statins

Between 2000 and 2008, 134 263 adults at the Brigham and Women's Hospital or Massachusetts General Hospital were prescribed a statin, the most common being atorvastatin and simvastatin. Of these, 57 292 (53.1%) stopped taking the statin at least once during the course of treatment. Just over two-thirds of patients had a reason documented in their records for the discontinuation, and the most common reason listed was "no longer necessary," although other reasons included cost, a change of statin was requested by the insurance company, switching to another drug, or the patient simply did not want to take it. In total, 2233 patients stopped because of an adverse reaction.

To heartwire , Turchin explained there is a gap between side effects reported by patients and statin-related events observed in the clinical trials. "Everyone who sees patients, myself, my colleagues, they'll tell you that many patients have side effects from what they think are the statins," said Turchin. "Many patients stop statins for this reason. On the other hand, if you look at the literature that comes from clinical trials comparing statins and placebo, the incidence of side effects in the statin arm is similar, if maybe a little bit higher, but not by much, to the adverse events of those treated with placebo. There is a discrepancy here."

In the analysis of all patients prescribed a statin, 18 778 (17.4%) of patients had a statin-related event documented during the study, including 27.0% of patients with myalgia or myopathy (rate of myalgia and myopathy was 4.7% in the overall population). Other events included musculoskeletal and connective-tissues disorders (2.5%), general disorders (2.3%), hepatobiliary disorders (2.1%), and gastrointestinal disorders (1.6%). In total, 0.006% of patients developed rhabdomyolysis, 0.06% reported memory problems, and 1.7% were drug intolerant.

Of the 18 778 patients who had a statin-related event, 11 124 stopped the statin temporarily. More than half of those who stopped the LDL-lowering drug were "rechallenged" with a statin over the following 12 months, and 90% of these rechallenged patients were taking a statin 12 months after the original statin-related event. Approximately 40% of these patients received the same statin. Following discontinuation, patients were rechallenged with 1.2 unique statins over the 12-month period following the adverse event. For the 3858 patients who stopped taking a statin and were rechallenged with a different drug, 13.2% had a second statin-related event.

"Sometimes patients might react only to a particular statin, but not another one," said Turchin. "Some statins are known to have more drug-drug interactions than others. Not all statins are created equal. On the other hand, sometimes a lower dose of the same statin will work, or sometimes the symptom might not have been caused by a statin at all."

Of the 46 168 patients who stopped taking a statin not because of a statin-related event but for other reasons, including undocumented ones, 66% had another statin prescription over the following 12 months, most of which were for a different statin. Of those who restarted, 98% were still taking the statin 12 months later.

Imagined and Bona Fide Statin Intolerance

Dr Scott Grundy (University of Texas Southwestern, Dallas), who wrote an editorial to accompany the study[2], said that the current clinical guidelines "virtually mandate" lifetime use of statins once they are started, although this can be a challenge for many patients. These new data do confirm that discontinuation rates are relatively high but are reassuring in that most patients can tolerate the drugs in the long term if they are rechallenged. He notes that many patients blame the medications for various side effects, a natural tendency.

"At least one-half of patients referred to the lipid clinic at my institution for statin intolerance have symptoms that are clearly unrelated to the drug," writes Grundy. "Even so, many patients cannot be convinced that statins are not the problem."

Still, "bona fide intolerance" is a real phenomenon, he adds, saying that 5% to 10% are intolerant to the drugs while approximately 10% to 20% have statin-associated muscle problems. The highest priority for statin adherence remains in patients with established cardiovascular disease, the secondary-prevention patient, as well as those with diabetes and chronic kidney disease. "Primary prevention in lower-risk persons is another matter," states Grundy. "Treatment guidelines for primary prevention are becoming increasingly 'aggressive' in use of statins. It is here that adherence will probably emerge as a major issue."