New Cholesterol-Drug Options Cut Heart Risks

"New options are emerging for people who are at risk of heart attacks and strokes but can't take or benefit fully from widely used cholesterol drugs.

Despite decades of progress against high cholesterol, as many as 30% of people prescribed the popular cholesterol-lowering pills known as statins don't take them or have to limit their doses because they can't tolerate the muscle pain that sometimes comes as a side effect. Others remain at risk of cardiovascular disease even when they are on full doses.

The failure to fully protect these millions of people is one reason heart disease remains the nation's leading killer after decades of lifesaving medical advances, a problem that deepened during the Covid-19 pandemic. "We are backsliding," said Edward Fry, president of the American College of Cardiology and a cardiologist at Ascension Indiana St. Vincent Heart Center in Indianapolis.

Research presented at a conference held by the ACC and the World Heart Federation in New Orleans over the weekend and on Monday provided new evidence for non-statin treatments to reduce cardiovascular risk: two daily cholesterol-lowering pills and an anti-inflammatory drug.

Cardiologists said they welcome new options to help patients who can't benefit enough from statins, many of whom are older, at high risk for heart disease and have other conditions such as diabetes. "We need to do whatever we can to lower LDL cholesterol," said Eugene Yang, a cardiologist at the University of Washington and medical director of the UW Medicine Eastside Specialty Center.

Drug development for heart treatments is undergoing a renaissance after years when generic brands took over sales of once-blockbuster cholesterol medications. The list of alternatives to statins includes drugs called PCSK9 inhibitors that sharply lower cholesterol but aren't widely used because they are costly. Statins, which are generic, cost just a few dollars for each prescription.

Statins reduce low-density lipoprotein (LDL) or "bad" cholesterol by slowing production of cholesterol in the liver and helping remove it from blood. Those actions reduce the risk of heart attacks and strokes.

A study with 13,970 patients in 32 countries showed that a daily pill, bempedoic acid, significantly lowered the risk of heart attacks, strokes and other cardiovascular complications in people intolerant of statins, according to results published in the New England Journal of Medicine and presented at the conference.

The drug, marketed as Nexletol by Esperion Therapeutics Inc., was designed to lower cholesterol without muscle pains by becoming active only once it enters the liver. Steven Nissen, lead author of the study and chief academic officer of the Cleveland Clinic's Heart and Vascular Institute, said the drug isn't meant to replace statins, whose efficacy has been widely studied. Bempedoic acid reduced cardiovascular risk similarly to other non-statins in the study, but was less effective at lowering cholesterol than PCSK9 inhibitors.

Nexletol and another version called Nexlizet that combines bempedoic acid with another non-statin cholesterol-lowering drug, ezetimibe, have been on the market since 2020, approved by the Food and Drug Administration and European Medicines Agency to lower cholesterol.

Cardiologists said they hope the new data make it easier for them to prescribe bempedoic acid to patients who can't take statins and want an oral drug rather than the PCSK9 inhibitor injections."We need more options in this huge group of statin-intolerant patients," said Timothy Hegeman, a cardiologist with UCHealth in Colorado Springs, Colo. How much it gets used will depend in part on the drug's cost to patients, Dr. Hegeman and others said.

Merck & Co. said Monday that it is making progress on a potential new PCSK9 inhibitor.

Another study published Monday in the Lancet and presented at the conference made the case for giving an anti-inflammatory drug to patients who are on statins yet remain at high cardiovascular risk.

The analysis of 31,245 participants found that a marker of inflammation in the body, C-reactive protein, was better at predicting the risk of a major cardiovascular complication or death than measuring LDL cholesterol.

Two trials have shown that an anti-inflammatory drug called colchicine lowered cardiovascular risk in patients on statins with heart disease, said Paul Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston and lead author of the study." [1]

1.  U.S. News: New Cholesterol-Drug Options Cut Heart Risks
McKay, Betsy.  Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 07 Mar 2023: A.3.