SNOWMASS, COLO. — When starting patients on statin therapy, it's important to acquaint them with the characteristic ways in which statin-associated myopathy differs from everyday aches and pains, Dr. Robert A. Vogel said at conference sponsored by the Society for Cardiac Angiography and Interventions.
Statins, he stressed, comprise a “tremendously safe class of drugs.” The most feared complication—rhabdomyolysis—is rare. A great many patients inappropriately stop taking their medication because they overinterpret the significance of their aches and pains, said Dr. Vogel, professor of medicine and director of clinical vascular biology at the University of Maryland, Baltimore.
Statin-associated myopathy involves symmetric large-muscle pain, usually associated with tenderness upon squeezing. It is often accompanied by weakness. In fact, in older patients muscle weakness very often predominates over pain.
“I tell patients it feels like the flu. You're sore all over. You're weak. And I think it's very helpful to provide a [creatine kinase] lab slip at the time you write a prescription for a statin. I tell the patient that if you get symmetric big-muscle pain and weakness, go to the lab and get this test drawn and call me. Four hours later I can get your CK, and we'll know what we're dealing with,” he explained.
The distinction between statin-associated myalgia and myositis is crucial. In myalgia, which is a benign condition, the serum CK level is within the normal range. Management involves reassurance, a change of statin, a lower dose, or 30 mg/day of over-the-counter coenzyme Q10, which Dr. Vogel has found works well in many of his patients, even though randomized trial results have been mixed.
In contrast, statin-associated myositis as defined by a CK level greater than 10 times the upper limit of normal dictates that statins be discontinued altogether.
However, statin-associated myositis with histologic muscle damage despite a normal CK result has been described (Ann. Intern. Med. 2002;137:581–5). This condition is thought to be rare and usually is linked with objective signs of muscle weakness.
Until Dr. Vogel began issuing CK lab slips when prescribing a statin, he found many of his patients who developed muscle soreness simply quit taking their medication and didn't inform him until they came in several months later for their scheduled liver function tests. By then it was be impossible to determine whether they'd had myalgia or myositis because a statin-related elevated CK would have returned to normal.
Benign statin-associated myalgias are common. In the landmark 10,001-patient Treating to New Targets (TNT) trial, for example, myalgia occurred in 4.8% of patients randomized to atorvastatin (Lipitor) at 80 mg/day and 4.7% on 10 mg/day. And therein lies an important lesson.
“By dosing up, which is often required to get patients to goal, we're not costing our patients more muscle pain. That's a key concept for consideration because you are not making your patients safer by keeping the dose of statins low,” Dr. Vogel stressed.
In the Collaborative Atorvastatin Diabetes Study (CARDS), the incidence of myositis was 0.1% with atorvastatin at 10 mg/day and 0.7% with placebo.
The complication of statin therapy every physician justifiably fears is rhabdomyolysis. It is marked by muscle symptoms accompanied by a greatly elevated CK—“I've seen levels of 300,000 IU/L,” Dr. Vogel said—along with elevated creatine and myoglobinemia. Rhabdomyolysis carries a 4% mortality rate.
But rhabdomyolysis is exceedingly rare. A Food and Drug Administration study of more than 250,000 statin users concluded that a physician with 2,000 patients on either of the two most widely prescribed statins—atorvastatin and simvastatin (Zocor)—for 20 years will encounter, on average, one case of rhabdomyolysis (JAMA 2004;292:2585–90).
'You are not making your patients safer by keeping the dose of statins low.' DR. VOGEL