Two years ago Sally Bell, now 67, started noticing weakness and achiness in her legs. “Maybe I’m not working out enough,” she thought. But then again, perhaps something else was wrong. “Yes, I’m older and I’m more sedentary than I used to be, but I’m not that out of shape,” says Bell. Finally she talked to her doctor. That’s when she realized she was experiencing side effects from the statin drug she’d starting taking. She stopped the drug and saw an almost immediate improvement. But even today, some of the damage remains.
Bell was one of millions of Americans prescribed a daily statin. Roughly one-quarter of all U.S. adults 45 and over — and 50 percent of men over 65 — now take one of these medications, which lower “bad” LDL cholesterol and also tamp down body-wide inflammation, a major factor in heart disease and other chronic conditions such as cancer and Alzheimer’s disease.
When statins first gained popularity for lowering cholesterol, doctors joked about putting them in the water supply. Now, despite the fact that statins are among the most-prescribed drugs in America (Lipitor currently tops the sales charts), many doctors believe that even more people should be taking them. That’s thanks in part to their ability to lower inflammation, and to new treatment guidelines recently released by the American Heart Association and the American College of Cardiology, which encourage doctors to consider a host of risk factors, such as age, gender, diabetes, high blood pressure, and smoking history (in addition to cholesterol), when deciding whether or not to put a patient on one of these drugs.
But like all medications, statins are not without risks. Many people who take them stop, often because of side effects. And as one prominent physician argues, if we led healthier lives, we might not need them.
Who Should Take Statins
Statins were originally designed to prevent second heart attacks in people with heart disease, and they do that job well. “Men and women with established heart disease benefit equally from statin therapy,” says Nieca Goldberg, MD, Medical Director of the Joan H. Tisch Center for Women’s Health at New York University’s Langone Medical Center.
Doctors also use statins to prevent first heart attacks and strokes in people deemed at increased risk. The drugs can benefit men and women with high LDL cholesterol — and also those with normal cholesterol but high levels of an inflammation marker known as C-reactive protein, or CRP, measured by the high-sensitivity CRP test. “The Jupiter full study showed that healthy men over 50 and healthy women over 60 who have normal cholesterol and a high-sensitivity C-reactive protein [score] of greater than or equal to 2 mg/L reduced the risk for a first heart attack more than 30 percent” when taking a statin, says Dr. Goldberg.
The new treatment guidelines state that anyone with a very high LDL (“bad” cholesterol) level — 190 mg/dL or higher — and anyone with a greater than 7.5 percent chance of having a heart attack or stroke or developing other forms of cardiovascular disease in the next 10 years, as indicated by an online risk calculator, should be prescribed a statin. Read the MedShadow blog about the new statin guidelines.
A Changing Safety Profile
As far as prescription medications go, statins are considered relatively safe — and yet, up to half of all people who start taking a statin stop, says David Katz, MD, Director of Yale University’s Prevention Research Center. Side effects such as muscle pain and cognitive changes including forgetfulness and fuzzy thinking are the major catalysts for stopping the medicine. The cognitive changes usually disappear once the drug is stopped.
MedShadow Note: With statins, the risk of myopathy is dose-related. The FDA-approved packaging insert notes the following about simvastatin, which is similar for all statins: In a clinical trial database in which 41,050 patients were treated with simvastatin with 24,747 (approximately 60%) treated for at least 4 years, the incidence of myopathy was approximately 0.02%, 0.08% and 0.53% at 20, 40 and 80 mg/day, respectively. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.
CoQ-10, a supplement, was shown in a study to effectively decrease mild to moderate muscle pain in about 1/3 of statin users and symptom improvement in 75% of statin users. Placebo users in the trial experienced no benefits (indicating actual effectiveness vs. a placebo effect).
Ironically, one recent study showed that the risk of these side effects is statistically insignificant when compared to the risk from a placebo (inert pill). The catch is that in clinical trials of statins, the nocebo, or negative placebo, effect is quite high, says Dr. Katz. So in reality, many people who take statins have very real side effects, even though many of those side effects are due to the nocebo effect. (Read the MedShadow blog about the Nocebo Effect.)
The newest safety concern around statins is perhaps also the biggest: Recent research has suggested that the drugs increase the risk of type 2 diabetes by 9 percent on average. Among women, the increase in risk is higher, says Dr. Katz. Despite this fact, many doctors believe the benefits outweigh the risks.
Liver damage is another potentially serious side effect. The FDA calls serious liver injury from statin use “rare,” to the tune of two or fewer cases per one million patients annually. Symptoms of liver disease include unusual fatigue, loss of appetite, pain in the right upper abdomen, dark urine, and yellowing of the skin or the whites of the eyes.
MedShadow Note: The FDA-approved package insert on Lipitor (atorvastatin) notes: HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (>3 times the upper limit of normal [ULN] occurring on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively.
Certain people may be more prone to side effects from statins than others, says Dr. Goldberg. These include older people and those who take multiple medications, have a small body frame, use a calcium channel blocker (brand names include Norvasc and Cardizem), take antibiotics such as erythromycin or clarithromycin, or drink grapefruit juice, which increases the effects of atorvastatin, simvastatin, and lovastatin, but not pravastatin or rosuvastatin, says Dr. Goldberg.
To minimize the risk of side effects, talk with your doctor about avoiding drugs and beverages that interact with your statin. Dr. Katz also recommends taking coenzyme Q10, aka coQ10, to treat or prevent muscle aches. “Most of my patients have done well with this,” says Dr. Katz.
If you experience side effects while taking a statin, talk to your doctor right away. He or she may switch you to a different statin, which often helps, or lower your dose. Or you may need to go off your statin altogether.
“Sometimes we need to use non-statin cholesterol medications in people who have side effects,” says Dr. Goldberg. Several types are currently on the market including drugs that bind to bile acids in the intestine, those that block the formation of LDL, and those that block the absorption of cholesterol from food. Other promising non-statin cholesterol drugs are currently being studied.
Under-Prescribed or Over-Prescribed?
“Statins clearly save lives, and could save many more,” says Dr. Katz. “People with dyslipidemia [bad cholesterol levels] and excess inflammation stand to benefit. Nearly 500,000 die of cardiac events each year in the U.S.; statins could reduce this toll substantially.” So in this sense, says Dr. Katz, statins are under-prescribed.
And yet, if more people followed a heart-healthy lifestyle, many of them would not need the drugs. Dr. Katz, author of Disease-Proof, believes that “if lifestyle were used as medicine, 80 percent of all heart disease could be eliminated, no prescription required.” He adds, “Using medication is not nearly as good, and yet we tend to neglect the power of lifestyle as medicine and rely on meds.”
Dr. Katz recommends losing extra weight, getting more exercise and following a healthy, mostly plant-based diet. One good choice is the Mediterranean diet, which includes plenty of fruits and vegetables as well as good-for-you fats from nuts, seeds, olives, avocados, and fish.
Trends in High LDL Cholesterol,Cholesterol-lowering Medication Use, and Dietary Saturated-fat Intake: United States, 1976-2010. (Centers for Disease Control and Prevention, March 2013)
FDA Drug Safety Communication: Important Safety Label Changes to Cholesterol-Lowering Statin Drugs (U.S. Food and Drug Administration)