Restenosis after coronary angioplasty

Abstract Coronary angioplasty is used to treat coronary disease in many patients. Indications for angioplasty have expanded since it was first performed, mainly as a result of improvement in equipment and techniques. one problem with coronary angioplasty is the phenomenon of renarrowing of the treated coronary lesion, a process called restenosis . The events that constitute restenosis appear to be a universal response to the arterial wall injury of angioplasty. They are currently characterized as follows: platelet adhesion and aggregation on the damaged endothelium and within deep splits into the tunica media; release of platelet-derived growth factors; inflammation of the mechanically injured medial zone; transformation of smooth muscle cells of the tunica media after their activation by several of the growth-promoting substances; migration and proliferation of transformed smooth muscle cells, with secretion of copious amounts of extracellular matrix material; and, finally, termination of the growth process with regrowth of endothelium over the injured area. A decade of research work has helped identify clinical correlates of restenosis after coronary angioplasty procedures. This work is hindered by lack of a uniform angiographic definition of restenosis. in addition, much of the information has come from small studies, with incomplete follow-up and retrospective orientation. Nevertheless, some data are available. Patient-related correlates include male gender, unstable angina, diabetes, and continued smoking after angioplasty. Lesion-related correlates include multilesional and multivessel procedures, higher postangioplasty residual stenosis, proximal vessel location, location in the left anterior descending artery, location in a vein graft, long lesions, and total occlusions. The only consistent procedure-related correlate has been incorrect sizing of the angioplasty balloon to the treated artery. For the purposes of individual patient care, clinical correlates are not helpful. No group of variables has been found to be associated with complete freedom from restenosis, and no group is completely predictive of restenosis. All patients undergoing angioplasty procedures require some follow-up through subsequent months and years. Symptom status and the results of noninvasive studies have been investigated for purposes of followup. Symptoms are virtually useless by themselves for predicting restenosis or its absence. When symptom status is combined with exercise thallium 201 scintigraphy performed 4 to 6 months after an angioplasty procedure, the two factors are less than ideal but have a negative predictive value of more than 90%. This means that more than 90% of patients who have neither symptoms nor evidence of ischemia by thallium 201 scintigraphy will not have angiographic restenosis. Application of this finding to clinical practice must be tempered by individual patient circumstances, such as whether the patient had symptoms before the angioplasty procedure and whether the potential area of ischemia is even discernible by thallium imaging. Numerous clinical studies have been performed to reduce or prevent restenosis. Almost all have been disappointing, but several have been encouraging. Studies of antiplatelet agents, such as aspirin, dipyridamole, and ticlopidine, have not shown efficacy. On the other hand, studies of an inhibitor of platelet-derived growth factor have been provocatively encouraging. No reduction in restenosis was found with the use of the anticoagulants heparin and coumadin. Fish oils have been found in several trials to provide modest but encouraging reductions in restenosis, but these results await further confirmation. Inhibitors of thromboxane, along with analogs of prostacyclin, have not been found to be effective. A panoply of other agents, including angiotensin-converting enzyme inhibitors, calcium-channel antagonists, β-adrenergic receptor antagonists, lipid lowering agents, and the antimitotic drug colchicine, have all been found to be ineffective. A number of other mechanical revascularization strategies, including atherectomy procedures and coronary stent devices, can achieve potentially better initial results than standard balloon angioplasty in some situations. Restenosis rates appear to be slightly lower in some groups with these procedures. Further research with these procedures is therefore necessary. Restenosis remains a clinical challenge, but better understanding of coronary artery disease and of its development and treatment will ultimately be derived from studies of the phenomenon of restenosis.