I have always downplayed the side effects of statins. In my mind, the benefits of statin drugs are so important, and the endpoint of statin therapy is so sound prognostically, that the minimal side effects statins have are inconsequential to the big picture. Stating it differently, a little discomfort is worth it when you realize a statin drug reduces your chance of a heart attack or sudden death. It’s difficult to grasp that fact, though, when it’s early in life and those harmful problems are still years away from happening.
A recent article on medscape.com discusses the many side effects of statins, where each stands in the realm of seriousness and long-term adverse effects, and how much, or even if, they warrant discontinuation of the statin.
In the package inserts for Lipitor, Lescol, Pravachol, Zocor, and Crestor there are “66 adverse events/outcomes listed.” To evaluate the importance of each of these 66 occurrences, 19 scientific studies involving 124,000 patients observed for 4.5 years were thoroughly investigated. Of the 66 listed adverse events, only 4 were found to occur often enough to be harmful in the long term. The other 62 events were determined not to cause significant harm.
The four adverse effects/outcomes that were visible or measurable were:
Elevated transaminase levels—liver enzyme tests were abnormal
Other liver function tests were abnormal
Changes in urine composition
Edema—swelling of the feet, legs, and ankles
Elevated transaminases, liver enzymes occurred with statins at a rate of 0.3% a year and with placebo at 0.22% per year. Statins affect the liver because it’s in the liver where they have their LDL-lowering effect. There is a dose-effect response to the liver meaning the higher the dose of statin, the greater the effect on the liver. Elevated transaminases over a long time, mean harm is occurring to the liver cells. If this goes undetected for long enough, liver toxicity and even liver failure may occur. Checking a patient’s blood liver enzymes a couple of times a year to look for elevated levels will avert long term problems.
Other liver function test abnormalities were found at a rate of 0.25% yearly, and have the same long term concerns as transaminases.
Changes in urine composition are a rare but serious adverse effect of statins some of which are potentially fatal. Blood and protein in the urine occur but don’t have the fatal consequences that myoglobinuria has. Myoglobin is the result of rhabdomyolysis, the process of muscle cell damage caused by statins. Myoglobin leaks into the bloodstream and clogs the kidney tubules as they filter the blood. Myoglobinuria causes kidney failure and is a potentially fatal medical emergency. Edema is a consequence of kidney failure.
The aforementioned adverse effects are rare, objective, measurable problems that are the result of statins. Numerous other subjective reactions occur, however, and foremost among those is the vague and variable symptom of muscle pain. Nearly 90% of the complaints of muscle pain by patients on statins cannot be attributable to the statin. If there is swelling or tenderness of the muscles plus elevation of CPK, a muscle enzyme, the statin is probably the cause. If after stopping the statin the muscle pain resolves, there is a good chance the symptoms are due to the statin. But when 27.1% of patients on statins and 26.6% of patients on placebo complain of muscle pain, an objective reason is hard to find.
“Statins increase the risk for newly diagnosed diabetes, and the effect is dose dependent.” Most new cases (62%) of diabetes occurred in patients whose baseline blood sugar was already in the highest 25%. Statins are dosed in terms of intensity of therapy. Statin dosing is
low, medium, or high in intensity. This is determined by the LDL-C level you’re striving to achieve. In high intensity statin therapy, the LDL-C goal is 55 mg/dL or less. It is this scenario that seems to raise fasting blood sugar and A1C levels. In several studies, high intensity statin therapy raised the A1C by 0.8 percentage points.
Adverse effects such as memory, cognition, depression, and sleep disorders are in the package insert’s list of 66, but there are no studies that substantiate statin drugs as their cause. My reference states “this concern appears biologically plausible given that cholesterol is essential for neuronal membranes and myelin [the protective coating over nerve fibers].” But the brain’s cholesterol metabolism operates independently of LDL-C metabolism. A causal relationship for stains and cognition has never been established.
Depression and sleep disorders are on the list of 66, but reviewing the science of these problems, there is no data to show any relationship with depression. In fact, studies have shown that statin users are actually at lower risk for depression than non-users. The same is true for sleep disorders.
Statins are continually fighting a battle against adherence (people stop taking them!). Many patients who experience muscle aches and pains blame them on the statin and stop taking the drug. Of course, that’s counterproductive and leads toward worsening arteriosclerosis and the consequences attendant to that. An analysis of 76 studies involving almost 6 million patients found that 37.6% of patients on a statin quit taking it. A German study involving 866K patients on statins showed that by day 300, approximately 71% of them had stopped their statin. After 36 months, only 20.6% remained on the drug. Statins have earned an undeserved reputation for causing muscle aches and pains and many patients stop the medication unnecessarily.
There’s no doubt statins have side effects but attributing those symptoms to the statin, there is not always a direct correlation. In my opinion, the good statins do toward primary and secondary prevention and for the prevention of sudden death should make patients try their hardest to stay on the medication regardless of adverse effects.
Reference: van den Huevel M. Statin Side Effects: What the Evidence Shows medscape.com 2026 October 5.
