Advances in Intracoronary Diagnostics and Therapeutics
12.04.2007: Drug Eluting Stents: Lessons in Biocompatibility
SPEAKER: Sahil A. Parikh, MD: HMS, BWH, MIT
MODERATOR: Thomas J. Brady, MD: MGH, HMS, CIMIT
The CIMIT Forum on Dec. 4 focused on “Advances in Intracoronary Diagnostics and Therapeutics,” and several heart specialists said that research must continue if the number of deaths from cardiovascular disease is going to diminish.
Speaking were Sahil Parikh, MD, Clinical and Research Fellow, Brigham and Women’s Hospital; and James Muller, MD, who is chief executive officer of InfraReDx, Inc., a company he helped create to provide better diagnostic tests to identify cardiovascular disease. Introducing the program was Ahmed Tawakol, MD, co-program leader, CIMIT Cardiovascular Disease Program; co-director, Cardiac MR-PET-CT Program; and associate director, Nuclear Cardiology, Massachusetts General Hospital.
Each year more than 1 million Americans suffer heart attacks. In many cases, the event is the first indication of heart disease, and is often fatal.
Experts say the cause of most heart attacks is rupture of a plaque in the coronary arteries followed by formation of a clot that blocks the flow of blood to the heart muscle.
Dr. Parikh said that until recently, use of drug-eluting stents (DES) has been a key strategy in treating such conditions. But a concern about toxicity has prompted cardiologists to be more cautions in recommending DES. He said that several years ago, cardiologists would call for a drug-eluting stent 90-95 percent of the time. Now doctors are recommending DES in about 75 percent of (appropriate) conditions.
Dr. Muller said that despite progress in dealing with heart disease, predicting serious heart attacks is still difficult. The company he founded, InfraReDx, Inc., is focused on providing improved diagnostic testing in predicting coronary episodes.
Dr. Muller, who once was closely involved with CIMIT, said that his company is working with the Food and Drug Administration in an attempt to receive approval for an improved tool for testing. Then the company will launch a large study to prove cost effectiveness.
The purpose of placing a stent in an artery is to prevent restenosis (re-narrowing of the artery) without causing thrombosis (the formation of a clot), for both restenosis and thrombosis can lead to heart attacks. Drug-eluting stents, which limit restenosis, were regarded as a major medical advance when they first appeared, but new evidence suggests that they also confer long-term risks. In a significant number of cases, particularly in patients who stop taking anti-clotting drugs, the stents have caused fatal thromboses years after their placement in an artery. To make drug-eluting stents as safe and effective as possible, researchers are seeking to improve the stents’ biocompatibility.
A stent is a foreign object in the body, and the body responds to the stent’s presence in a variety of ways. Amongst other responses, macrophages accumulate around the stent, and nearby smooth muscle cells proliferate. These physiological changes, which can cause restenosis, can be limited by drugs released by the stent, but these drugs also limit re-endothelialization. This lack of healing can make the stent an exposed surface on which a life-threatening clot can form.
The safety and effectiveness of a drug-eluting stent depends on its design and on its materials. The structure of a stent’s metal backbone, for example, has a significant effect on the amount of endothelial denudation that the stent causes. When comparing drug-eluting stents to bare-metal stents, one should remember that drug-eluting stents are only beginning to adopt the sophisticated structures that are commonly used in state-of-the-art bare-metal stents. The properties of the drug used in a drug-eluting stent are also extremely important. Hydrophobic drugs are more likely to be retained in the arterial wall than hydrophilic drugs, and for all drugs, the concentration varies with wall depth. Finally, the polymer coating of a drug-eluting stent influences the stent’s tendency to cause a clot.
In the future, researchers hope to create stents, or at least polymer coatings, that will degrade in the body over time. This project will require expertise in both materials science and medicine.
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