A patient Iâ€™ll call Sandy came to me with severe muscle pain and cramping after taking a statin medication to lower her cholesterol.Â After running some tests, I found her muscle enzyme levels were above normal and clearly she was having problems due to a well known side effect of this class of drugs. Sandy needed more helpâ€”we couldnâ€™t ignore either her muscle pain or her high cholesterol.Â
Which brings me to the main point of this blog: What do you do if your cholesterol is high, but you canâ€™t tolerate the medications your doctor is using to correct the problem?Â If you are one of the 3%â€“4% of people who donâ€™t do well with a statin drugâ€”maybe they donâ€™t work to lower your cholesterol or they cause side effects like liver inflammation or muscle damageâ€”you have other choices for medications.Â Keep in mind that all medications have a risk and benefit profile.Â This means that you need to weigh the risks along with the benefits and see whether itâ€™s worth it to take that drug. Of course, you want to make this decision together with your doctor.
Like the statins, fibrates reduce the bodyâ€™s cholesterol production, but they are less effective in lowering LDL (â€œbadâ€) cholesterol levels. In other areas, though, fibrates actually have the edge. They are substantially better at boosting HDL (â€œgoodâ€) levels, and only two statins, atorvastatin (Lipitor) and rosuvastatin (Crestor), can match their ability to reduce triglyceride levels.
Gemfibrozil (Lopid) and fenofibrate (TriCor) appear equally safe and effective. Fenofibrate is more convenient, since it is taken once rather than twice a day, but generic gemfibrozil is substantially less expensive. The fibrates are particularly effective in patients with high triglycerides, low HDL, or diabetes. However, some patients with high triglyceride levels may experience a paradoxical rise in LDL levels. Side effects are uncommon but can include liver inflammation, muscle damage, abdominal pain, gallstones, dizziness, and interactions with the anticoagulant (â€œblood thinnerâ€) warfarin (Coumadin).
Fibrates should not be taken by patients with advanced liver or kidney disease, and they should not be combined with a statin except under very strict medical supervision, including careful monitoring for muscle damage. While the risk of muscle damage from either statins or fibrates alone is small, a Harvard study found that the combination of a statin and a fibrate increases that risk more than sixfold.
Unlike other cholesterol-lowering medications, which are absorbed into the body, resins remain in the intestinal tract, where they latch onto bile acids, preventing them from being absorbed into the bloodstream. Because the liver uses bile acids to produce cholesterol, the net effect is to lower LDL levels, but in a few patients, triglyceride levels may rise.
Although resins are effective and have few serious side effects, they have not been widely used. Thatâ€™s because many patients find them unpalatable due to bloating, constipation, and nausea. But the resin colesevelam (WelChol) appears to have fewer of these side effects, and it is proving particularly useful as add-on therapy for patients who do not respond fully to other drugs, including statins. Resins can interfere with the absorption of other medications, including digoxin, thyroid hormones, and some beta blockers, calcium-channel blockers, and diuretics.
Ezetimibe (Zetia) blocks the intestinal absorption of cholesterol in a different way than the resins do. On its own, a 10-mg dose can reduce LDL cholesterol levels by 17%â€“19%, a major benefit. When added to a statin drug, ezetimibe can produce additional LDL reductions of about 25% without boosting the risk of statin side effects. Ezetimibe can enable some patients who experience side effects from high-dose statins to reduce the dose to one that is tolerated. As a result, the FDA has approved a preparation combining simvastatin and ezetimibe in a single tablet (Vytorin). Ezetimibe has remarkably few side effects; a few patients may develop mild diarrhea.
Niacin (nicotinic acid) is a natural vitamin, vitamin B3, and itâ€™s available both over-the-counter and with a prescription. It also has the best effect on HDL cholesterol as well as an excellent ability to lower triglycerides and a good ability to reduce LDL levels. But that doesnâ€™t mean niacin is right for you. To improve your cholesterol levels, youâ€™ll need 20â€“200 times more niacin than the Dietary Reference Intake of 15 mg a day. At those doses, niacin has potentially serious side effects. Whether you get it with a doctorâ€™s prescription or on your own, treat niacin as a serious drug. Use it only if you must, always under medical supervision.
The many niacin preparations fall into two categories, crystalline and controlled release. Crystalline niacin is quickly absorbed and rapidly metabolized, so itâ€™s usually taken two or three times a day, ideally at the end of a meal (but not with hot foods or beverages). Many patients experience unpleasant itching, flushing, and headaches, particularly as the dose is slowly increased. This side effect can be minimized by taking an 81-mg aspirin tablet 30â€“60 minutes before taking niacin.
Controlled-release preparations are much less likely to produce flushing and itching; however, they are more likely to produce liver inflammation, to raise blood sugar levels in diabetics, and to trigger gout by raising uric acid levels. Other side effects can include fatigue, blurred vision, nausea, peptic ulcers, and impotence. Because over-the-counter preparations are sold as dietary supplements, not drugs, they are not regulated by the FDA and so vary widely in efficacy.
Statins are the undisputed stars of the cholesterol-lowering medications. Itâ€™s a lofty position that is well deserved, and itâ€™s likely to endure even as scientists develop new and better medications, including a new generation of â€œsuper-statins.â€ But behind every star is a supporting cast, and in the case of cholesterol, the second- and third-choice drugs can have first-rate benefits, either alone or together.
Have you had side effects while taking statins or another drug? What did you do about them?
Lowering Your Cholesterol
The Harvard Medical School Guide to Lowering Your Cholesterol (McGraw-Hill; April, 2005) provides the most expert, up-to-date advice on reaching and maintaining healthy cholesterol levels. It covers medications for cholesterol, nutrition, exercise, and alternative approaches, as well as how to work best with your doctor to develop the best cholesterol control treatment plan for you.