Some Docs in Denial About Statin Side Effects

For many patients who need to lower lipids to protect their heart health, statins are a blessing. But for some, these medications also cause troublesome side effects that their doctors ignore or don't recognize.

According to a recent survey of 650 patients, doctors dismissed or ignored patients' concerns about statin side effects more often than they acknowledged them.¹ Among the symptoms encountered by patients were muscle pain, cognitive deficits, and finger and toe numbness—all side effects reported in the literature, says Beatrice Golomb, MD, PhD, the study's lead researcher and an associate professor of medicine at University of California, San Diego (UCSD).² (It should be noted, however, that some research suggests statins may offer neuropathy protection [DOC News, August 2007, page 1]).

“What's troubling is that even for the best recognized side effects, which are the muscle effects, about 50% of these patients' physicians reportedly dismissed the possibility of a relationship to their statin medications,” Golomb says. “That suggests holes in physician awareness that are gaping.”

What might account for physicians' lack of side-effects awareness? John LaRosa, MD, president and professor of medicine at State University of New York Downstate Medical Center in Brooklyn, whose recent research has focused on intensive lipid lowering with statins, offers one possibility.

He says that physicians often think in terms of statistics and take their cues from the randomized trials on statin drugs. “The bias... is from all those trials that showed patients taking statins had the same level of adverse symptoms as patients given placebo,” LaRosa says.^3–8 “But of course there are no absolutes, and some patients clearly do experience adverse effects that we need to explore.”

MISCONCEPTIONS ABOUT STATINS

Respondents for the ongoing UCSD Statin Effects Study were recruited through Internet, newspaper, and television reports about the survey. Most were college-educated U.S. citizens. The mean age was 63 years, and men and women were about equally represented.

Golomb says this survey and other data her team has reviewed point to several commonly held erroneous beliefs about statins:

1. Myth: Muscle-related side effects are limited to muscle pain. According to the recent National Lipid Association Statin Safety Task Force report, statin-related muscle symptoms (generally referred to as myopathy) can include muscle pain as well as more general soreness, weakness, and cramps.⁹

   “The statin association is often made with bilateral and proximal muscle pain, but there can definitely be exceptions to pay attention to,” LaRosa says.

2. Myth: Only an elevated creatine phosphokinase (CPK) test indicates a statin-related muscle effect. “Some physicians may assume that if a patient's CPK is not elevated, then there cannot be a statin association,” Golomb says. “But this is repeatedly refuted in the literature. Patients with minimal or no CPK elevation can still have reversible myopathies that are impacting their quality of life.”

3. Myth: Statins only help—they do not hurt—cognitive abilities. While several high-profile studies have linked statin use to lower incidence of dementia, to date they have been uncontrolled, observational studies.^10–12 “That sort of study design has repeatedly led people astray,” Golomb says. “It's the same design that showed estrogen use dramatically lowers rates of Alzheimer's disease. Of course, in the high-quality matched studies, hormone replacement therapy actually increased risk of dementia.”^13,14

   Two randomized, double-blind, placebo-controlled trials found that statins may cause cognitive decrements—such as loss of memory and concentration—in some patients taking statins.^15,16 However, two other randomized trials found no such effect.^4,17

   “What makes us believe these negative effects can be statin-related is that, for many people, they reverse then recur with statin rechallenge,” Golomb says.

4. Myth: Side effects only surface during early stages of treatment. “We've seen that side effects can develop long after a patient has started on statins,” Golomb says. Increasing age raises the risk for adverse effects, as do several medications commonly prescribed for aging adults. These medicines can adversely interact with statins.⁹

ADDRESSING PATIENT COMPLAINTS ABOUT STATINS

The survey results indicate a need for increased physician sensitivity to potentially negative effects of statins, even though statins are well studied and, for the most part, safe, LaRosa says.

Take time to interview patients with an ear toward other possible sources of their symptoms, he suggests. If symptoms are vague and clearly not signs of a dangerous adverse event (e.g., rhabdomyolysis), it may help to urge patients to take a wait-and-see approach and to reassure them about benefits versus risks of their medication.

Indeed, though statin therapy is well proven to reduce cardiovascular disease (CVD) risk in patients with diabetes, in those with presumed statin intolerance, a very low dose of a more potent or less lipophyllic statin and/or the use of nonstatin agents such as fibrates, niacin, cholesterol absorption inhibitors, or bile-acid sequestrants can be tried, says John Buse, MD, PhD, CDE, American Diabetes Association president for medicine and science and chief of the endocrinology division at University of North Carolina School of Medicine in Chapel Hill. The primary issue is that these latter therapies have not been tested as rigorously as statins; it is not yet known if they reduce the risk of CVD as substantially as statins do, says Buse. A secondary issue is the reported risk of rhabdomyolysis in combinations of statins with fibrates or niacin.

When unexplained troublesome symptoms persist in patients on statins, they may benefit from a “statin holiday” with their physician's guidance, suggests cardiologist Gerald Gau, MD, professor of medicine at Mayo Clinic in Rochester, Minn.

Gau suggests having patients stop taking their statin medications for several days to see if symptoms resolve. If they do, the statin can be reintroduced to see if symptoms return, he says. Golomb suggests up to 2 months may be required for patients' statin-associated symptoms to resolve after discontinuing their medication.

The American Heart Association (AHA) offers the following recommendations for prescribing and monitoring statins:¹⁸

1. Because the risk of side effects tends to increase with statin potency, prescribe a dosage no greater than what is needed to achieve each patient's therapy goals. (The National Cholesterol Education Program suggests starting at a moderate dosage and gradually increasing it.)¹⁹

2. Select statins based on the degree of LDL-lowering needed and the potential for side-effects in each patient. AHA lists the following statins, in order of increasing LDL-lowering potency per milligram: fluvastatin, lovastatin or pravastatin, simvastatin, atorvastatin, and rouvastatin.²⁰

3. Consider using combinations of cholesterol-lowering drugs at lower doses for patients at increased risk for myopathy. These patients may include the elderly (ages _–>80 years), patients with small body frames, patients with multisystem disease (for example, chronic renal failure, especially caused by diabetes), and those on multiple medications.²⁰

4. Report any adverse events to the Food and Drug Administration to optimize the post-marketing surveillance system. ▪