AHA 2010: Options for Lowering LDL-C in the Statin-intolerant Patient

How should cardiologists define “statin-intolerance” and what is the best approach to managing lipids in patients who truly are statin-intolerant? At what point should a clinician give up on statins? “We know how great statins are, so trying to aim for the best way to get a statin on board is the first area to explore,” during lipid-lowering therapy said Christopher Cannon, MD, during a presentation at the American Heart Association Scientific Sessions 2010.

Cannon, a cardiologist with Brigham and Women’s Hospital in Boston, reminded the audience that confirming whether a patient is statin-intolerant and then finding the optimal statin and dose “may take multiple conversations with the patient, and trial and error to determine why the patient has been deemed intolerant. Ten times more people say they’re intolerant than actually are. There may be some bias by the patients on side effects.”

He suggested several preliminary steps that cardiologists and other physicians should consider before moving away from statins:

• Determine if side effects such as muscle aches and weakness are really a side effect of the statin or can be attributed to other causes. Cannon said that “You don’t want to dismiss the patient’s symptoms, so more questions will help determine the cause.”
• Try a drug holiday and then rechallenge later at the same standard dose to see if the pain recurs. “This would be more for knee pain or atypical pain rather than myalgias,” Cannon said.
• Switch to a different statin.
• Adjust the dosing of the statin. For example, Cannon noted that rosuvastatin is quite potent, so a reduced dose of 5 mg three times a week may also produce benefits.

If after trying all of this a clinician determines that the best decision is to switch from a statin to another medication, they should be aware that researchers are divided on the merits of some alternatives. Allen Taylor, MD, Washington Hospital Center in Washington, DC, said that although there is no perfect option, he thinks that niacin is the best non-statin alternative. Taylor said that niacin has been in clinical use for about 50 years and “has Food and Drug Administration clearance to do the things doctors want to do with it.”

According to Taylor, the problem with drugs that focus only on LDL reduction is that although half of the US population has a lipid problem, only half of that subset has an LDL problem; if a physician focuses only on LDL, he or she missing the other half of patients who have HDL or triglyceride problems. Taylor said that niacin lowers LDL about 10-15%, lowers triglycerides, and raises HDL about 20-25%. “It’s not just about LDL in your patients. They are dyslipidemic in large part and that’s why treating HDL and triglycerides should be part of treatment,” he said.

There are some limitations that cardiologists and other physicians should keep in mind when using niacin to treat this patient population. Taylor said that niacin is “not a quick fix, and it can be a long road to treating dyslipidemia. Niacin guidelines don’t tell you what your targets are for HDL and LDL. The guidelines also don’t tell you what the dosing is for niacin. What niacin does offer is a long, successful track record for outcomes.”

Robert Guigliano, MD, Associate Physician in Cardiovascular Medicine at the Brigham and Women’s Hospital and Assistant Professor of Medicine at Harvard Medical School, made the case for ezetimibe as a second agent for patients who don’t achieve their LDL goals or for patients who cannot tolerate statins. “It’s very clear that ezetimibe blocks cholesterol absorption and more cholesterol is brought out of the bloodstream,” Guigliano said. The drug has been proven safe while lowering LDL consistently by about 18%, regardless of which statin it is used with or at what dose, he said.

“The fact that you can block both major ways in which the body generates cholesterol -- absorption and synthesis -- when you combine ezetimibe with a statin makes it the most powerful combination of drugs available. No matter what statin you use, you can always beat it when adding ezetimibe,” Guigliano said.