Drug-eluting Stent Thrombosis


Journal of Pharmacology and Therapeutic Research is an open access, peer reviewed journal that focuses on the interdisciplinary research offering therapeutic solutions to various neurological, genetics, psychological, and respiratory issues affecting the human beings.

A drug-eluting stent (DES) is a peripheral or coronary stent (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots (thrombi), could otherwise block the stented artery, a process called restenosis. The stent is usually placed within the peripheral or coronary artery by an interventional cardiologist or interventional radiologist during an angioplasty procedure.

Drug-eluting stents in current clinical use were approved by the FDA after clinical trials showed they were statistically superior to bare-metal stents for the treatment of native coronary artery narrowing, having lower rates of major adverse cardiac events (usually defined as a composite clinical endpoint of death + myocardial infarction + repeat intervention because of restenosis). The first drug-eluting stents to be approved in Europe and the U.S. were coated with paclitaxel or an mTOR inhibitor, such as sirolimus.

Although drug-eluting stents continue to represent a major medical advance for angioplasty, evidence has always shown new clot thrombosis formation with stents to be a problem, thus clotting suppressant agents are routinely given during placement, and anticlotting agents should be continued; the question is for how long. Coronary arterial healing occurs after the placement of a drug-eluting stent, but complete healing of the vessel takes time. For drug-eluting stents, the time course of complete healing in humans is unknown.

A stent is a foreign object in the body, and the body responds to the stent’s presence in a variety of ways. Macrophages accumulate around the stent, and nearby smooth muscle cells proliferate. These physiological changes, which can cause restenosis, are limited by the drugs released by the stent, but these drugs also limit formation of a new endothelial layer over the new stent to inhibit clot formation. Endothelialization is a hallmark of vascular healing and is important for the prevention of thrombus formation. Lack of healing caused by anti-proliferative drugs can make the stent an exposed surface on which a clot, sometimes life-threatening, can form. For drug-eluting stents (which, by design, delay formation of a new endothelium cover over the stent), the incidence of clot formation within the stent may persist for a longer period of time, perhaps as long as five years after treatment. Drug-eluting stents have been associated with delayed arterial healing and the prevalence of latent thrombus after five years, suggesting patients may continue to be at risk for stent thrombosis for an extended period of time.

Though less frequent with drug-eluting stents, neointimal proliferation can still occur in DES and cause restenosis. Stent occlusion because of thrombosis may occur during the procedure, in the following days, or later. The presence of thrombi around the stent may, in turn, affect the drug-eluting performance of the stent. Treatment with the antiplatelet drugs aspirin and clopidogrel appears to be the most important factor reducing this risk of thrombosis, and early cessation of one or both of these drugs after drug-eluting stenting markedly increases the risk of stent thrombosis and myocardial infarction. A recent histopathology study showed very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis and correlate with the extent of stent malposition.

With Kind Regards,
Mark Orwell
Managing Editor
Journal of Pharmacology and Therapeutic Research

Email:  pharmacology@alliedresearch.org