Atherosclerosis Drug Therapies, Present and Future

By Jeni Baker

A leading cause of heart attack, stroke, and other medical issues, atherosclerosis -- also called “hardening of the arteries” -- is a condition in which fatty deposits build up inside artery walls, obstructing blood flow and sometimes shedding dangerous debris into the bloodstream.

Duke cardiologists Richard Becker, MD, and Robert Harrington, MD, discuss current atherosclerosis drug therapies of today and those being developed for future use.

Richard Becker, MD and Robert Harrington, MD

What Drugs Are Used to Prevent and Treat Atherosclerosis?

Commonly prescribed atherosclerosis drugs include:

• Lipid-lowering compounds, such as statins and niacin, which reduce blood levels of fats such as cholesterol and triglycerides
• Antithrombotic drugs -- including warfarin, low-dose aspirin, and clopidogrel -- which, by thinning the blood, prevent further plaque accumulation, mitigate injuries from blood clots caused by atherosclerosis, and treat heart disease

While countless people benefit from these therapies, there’s always room for improvement, as in the case of antithrombotic compounds. Some patients, for example, are unknowingly resistant to these drugs. Others appear to experience a “rebound effect” when they stop taking them, possibly putting them at risk for blood clots.

Becker -- along with other researchers at Duke Heart Center and the Duke Clinical Research Institute -- is among those tackling these issues.

“Using the world’s only model of its kind, our research focuses on developing new drugs that inhibit excessive blood clotting -- and antidotes to quickly reverse their effects -- with the aim of creating highly personalized medicines that can be used safely in a variety of patients,” Becker says. “Duke is coordinating national and international megatrials aimed at developing these drugs in common clinical settings.”

Why Are Megatrials Important When Developing New Drugs?

Megatrials -- those involving at least 1,000 people -- are considered the gold standard in clinical drug studies, and are critical to developing safe, effective new therapies for atherosclerosis and other diseases.

“To best understand the potential benefits and risks of a new therapy, it’s important to test it in the kinds of patients and settings in which it will ultimately be used,” says Harrington. “This typically requires very large clinical studies -- or megatrials -- as well as international collaboration among researchers. Megatrials enable clinicians to be confident about a drug’s effects when it’s used in clinical practice.”

The landmark Heart and Estrogen/Progestin Replacement Study (HERS), led at Duke by Kristin Newby, MD, illustrates this point.

HERS, which studied 2,763 women with heart disease, debunked the belief that hormone replacement therapy (HRT) helped prevent and treat atherosclerosis and other types of heart disease in women. HERS revealed that while HRT can reduce blood lipid levels, it provides no significant protection against future heart attacks or death from heart disease -- and is actually harmful to some women.

What’s Next for Atherosclerosis Drugs?

The future of atherosclerosis drugs is likely to lie in genome-guided therapies. Tailored to each patient’s genetic composition, these therapies would eliminate issues such as resistance to antithrombotic drugs.

“Ongoing genetic and genomic research will identify people at risk for heart attacks by examining the properties of their platelets, the genes that govern platelet behavior, and molecular profiles that characterize an individual’s propensity to form blood clots,” Becker says. “These studies may eventually enable doctors to select heart and vascular disease drugs based on each patient’s unique genomic signature.”

Investigators at Duke’s Clinical Research Institute and Institute for Genome Sciences & Policy currently are working with an international team to study new antiplatelet therapies and anticoagulants, as well as novel approaches to lowering cholesterol and controlling blood sugar in atherosclerosis patients.

“By studying blood samples from participants in many of these clinical trials, we can learn more about the genetic predictors that determine which patients respond well and which are more resistant to the therapies,” says Harrington. “The hope is that this will ultimately enable us to treat people with atherosclerosis in a highly personalized way.”

-- Harrington is director of the Duke Clinical Research Institute and a professor of medicine at Duke.

-- Becker is the director of the Duke Cardiovascular Thrombosis Center, co-director of Duke’s Hemostasis and Thrombosis Center, and a professor of medicine at Duke.