Cleveland—A new study documents muscle-related symptoms in patients with a history of statin-intolerance and determines which drug is a more effective option to lower their cholesterol.

The report, published recently by JAMA and simultaneously presented at the American College of Cardiology’s 65th Annual Scientific Session in Chicago, is the first major trial of its kind. It is significant because so many patients—5% to 20%—with clinical indications for statin treatment report inability to tolerate evidence-based doses, most commonly because of muscle-related adverse effects.

Cleveland Clinic researchers employed a blinded rechallenge with atorvastatin or placebo to confirm the presence of muscle-related symptoms in patients with a history of intolerance to multiple statins. In a second phase of the study, they determined that the PCSK9 inhibitor evolocumab was more effective than ezetimibe in lowering cholesterol for those patients.

Participants were 511 patients with very high levels of LDL cholesterol—averaging more than 210 mg/dL—as well as a history of muscle-related statin intolerance, with more than 80% of participants previously reporting intolerance to three or more statins. Results indicate that 42.6% reported muscle pain or weakness on atorvastatin, but not placebo, and 26.5% on the placebo, but not atorvastatin.

“Statin intolerance has been a very challenging clinical problem,” lead researcher Steven Nissen, MD, chairman of Cardiovascular Medicine, said in a Cleveland Clinic press release. “The study showed that PCSK9 inhibitors can significantly lower cholesterol in patients with documented statin intolerance, providing an effective treatment for these difficult to manage patients.”

Participants who demonstrated statin intolerance only on atorvastatin were randomized to two alternative treatments to lower LDL cholesterol—evolocumab or ezetimibe. Results indicate that, on average, patients showed a 52.8% reduction on evolocumab compared with 16.7% reduction with ezetimibe and there was little difference in muscle-related adverse effects.

Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, is an injectable nonstatin cholesterol-lowering drug self-administered once per month. Ezetimibe, used as the control in the trial, lowers LDL by decreasing the absorption of cholesterol in the small intestine.

“These findings demonstrate that both drugs are unlikely to provoke muscle symptoms and can be administered successfully in such patients, although with significant differences in lipid-lowering efficacy,” study authors conclude. “Since a minority of patients achieved optimal LDL-C levels despite treatment with evolocumab, it may be worth exploring the addition of ezetimibe to evolocumab for those patients requiring further LDL-C reduction. It should be noted that neither ezetimibe nor evolocumab is approved for reduction of major adverse cardiovascular events.”

« Click here to return to Weekly News Update.