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Member Research & Reports

Member Research & Reports

Iowa Study Evaluates Safety of Drugs Used to Dramatically Lower Levels of Bad Cholesterol

Heart disease patients taking an investigational class of drugs to achieve very low levels of cholesterol do not experience an increase in adverse events, including memory impairment or nervous system disorders, but may have an increased risk of cataracts, according to a study led by a UI College of Public Health researcher.

[Photo: Dr. Jennifer Robinson]

The new class of drugs – called PCSK9 inhibitors – were studied in combination with statins to lower LDL cholesterol, or bad cholesterol, in high-risk patients who were unable to achieve desired cholesterol levels using only statins or other lipid-lowering therapies.

The study sought to address concerns about how very low levels of LDL cholesterol effect body functions that rely on cholesterol, including hormone production, digestion, and healthy cell structure.

“The safety of these new drugs is critical to patients who have no other means by which to control their life-threatening high cholesterol,” said the study’s lead author Dr. Jennifer Robinson, Iowa professor of epidemiology and medicine and director of the Iowa Preventive Intervention Center. “The long-term effects of very low levels of LDL cholesterol are under evaluation in ongoing large clinical trials.”

The study appears in the February 7, 2017, issue of the Journal of the American College of Cardiology, which was published online Jan. 30, 2017.

Researchers pooled data from 14 randomized, controlled studies that included 5,234 patients treated with the PCSK9 alirocumab for up to two years. They looked for the occurrence of adverse events in patients who achieved two or more consecutive LDL cholesterol values of less than 25 mg/dL or less than 15 mg/dL. An LDL level of 25 md/dL was used because it has been suggested to be the level needed for normal cell function.

The overall incidence of adverse events was similar in patients taking alirocumab versus those taking placebo. Adverse symptoms monitored included musculoskeletal disorders, neurologic and neurocognitive conditions (including memory), and renal or liver problems. There was not an increased incidence of diabetes, despite previous studies showing an excess of diabetes in patients with LDL cholesterol lower than 30mg/dL on statin therapy.

Analyses did show an increased incidence of cataracts in patients with LDL less than 25 versus greater than 25. It was not clear what caused this increase, although researchers said it could be because reducing cholesterol accelerates underlying aging-related changes, contributing to cataracts.

While the investigation suggests the very low levels of LDL cholesterol were well-tolerated in limited trials, the long-term effects of PCSK9 inhibitors remain unknown, according to Robinson. As a result, she said statins remain the mainstay of cardiovascular risk reduction therapy.

“Statins have an excellent record of safety in properly selected patients,” said Robinson. “Therefore, every effort should be made to maximize statin therapy before considering adding a nonstatin such as alirocumab to further reduce LDL-C levels.”