Enhanced Long-Term Antiplatelet Therapy after Coronary Stenting
Enhanced Long-Term Antiplatelet Therapy after Coronary Stenting
Since the introduction of coronary stenting to interventional cardiology in 1989, improvements in stent implantation techniques and antiplatelet drug therapy have dramatically improved the short-term and long-term outcomes of percutaneous intervention, and stenting is now routinely performed in 90% of all percutaneous coronary interventions (PCI). Coronary stenting was initially approved for treatment of the acute complications of balloon angioplasty: by providing a mechanical scaffold for the vessel wall, sealing dissections and preventing elastic recoil, stents reduce the risk of abrupt vessel closure (Figure 1). As a result, emergency coronary artery bypass graft (CABG) surgery is now required in fewer than 1% of stent procedures compared with 5% of conventional balloon angioplasty procedures.
(Enlarge Image)
Cutaway view of a coronary artery showing a stent implanted to treat a previously flow-limiting stenosis. Reproduced from Herrmann[135] with permission from the Massachusetts Medical Society.
The demonstration in the mid-1990s that coronary stenting reduced angiographic restenosis rates in large-diameter vessels from the 3040% rate seen with balloon angioplasty to 1020% primarily by eliminating elastic recoil and negative vascular remodeling heralded the present era of elective stenting. The benefits of stenting over balloon angioplasty in reducing angiographic restenosis, target vessel revascularization and clinical event rates are now well established for small-vessel, saphenous graft, and restenotic lesions, as well as for chronic coronary artery occlusion and acute myocardial infarction. Increasing use of stents for more complex lesion types (diffuse, small-vessel and bifurcated lesions) and in high-risk settings (e.g. , diabetic patients) has, however, highlighted the problem of in-stent restenosis. Two recent breakthrough technologies brachytherapy (intracoronary radiation) for the treatment of in-stent restenosis and drug-eluting stents for (primarily) the prevention of restenosis have largely resolved this issue. By allowing controlled release of antiproliferative agents directly to the injured endothelium, drug-eluting stents offer the prospect of virtually eradicating in-stent restenosis, especially of the diffuse variety. Two drug-eluting stents the sirolimus-eluting CYPHER™ stent (Cordis/Johnson & Johnson, Miami, Florida) and the paclitaxel-eluting TAXUS™ stent (Boston Scientific Corporation, Natick, Massachusetts) are currently approved in the U.S. by the Food and Drug Administration (FDA) for prevention of restenosis in native coronary arteries.
From its inception, PCI has been intended as a focal treatment of flow-limiting coronary stenosis associated with discrete culprit lesions. However, in addition to providing lasting improvement in luminal patency, the ultimate goal of percutaneous coronary revascularization is to prevent morbidity and mortality arising from ongoing atherosclerosis in nonstenotic coronary segments. Coronary atherosclerosis is a diffuse, multifocal disease process that affects the entire coronary arterial tree, and patients with acute coronary syndromes are likely to have multiple sites of coronary plaque ulceration. Recurrent ischemic events after PCI are often due to atherosclerotic disease progression at sites removed from the culprit lesion, and serial angiographic studies indicate that most myocardial infarctions occur at sites previously associated with only mild or moderate luminal stenosis. This extensive, pan-coronary deterioration in non-culprit lesions may reflect a diffuse destabilization of atherosclerotic plaques after the initial ischemic event. Moreover, plaque vulnerability and liability for ischemic events are determined more by the biological properties of the coronary plaque than by the degree of vessel stenosis. Indeed, vulnerable plaques are frequently not severely stenotic prior to rupture, as the accumulating atheroma is accommodated by positive vascular remodeling, thereby offsetting the reduction in lumen size. The detrimental effects of progressive atherosclerosis on the long-term efficacy of PCI are seen in the frequent need for repeat revascularization in patients with multivessel disease and the high ratio of new lesion-to-target lesion restenosis in those with saphenous vein grafts.
Accumulating evidence of the diffuse nature of coronary artery disease, coupled with the inherent difficulties involved in identifying and treating multiple individual lesions, underlines the importance of adjunctive systemic pharmacotherapy and risk factor modification post-PCI in stabilizing atherosclerotic plaques throughout the coronary vasculature and reducing the likelihood of further ischemic events.
Since the introduction of coronary stenting to interventional cardiology in 1989, improvements in stent implantation techniques and antiplatelet drug therapy have dramatically improved the short-term and long-term outcomes of percutaneous intervention, and stenting is now routinely performed in 90% of all percutaneous coronary interventions (PCI). Coronary stenting was initially approved for treatment of the acute complications of balloon angioplasty: by providing a mechanical scaffold for the vessel wall, sealing dissections and preventing elastic recoil, stents reduce the risk of abrupt vessel closure (Figure 1). As a result, emergency coronary artery bypass graft (CABG) surgery is now required in fewer than 1% of stent procedures compared with 5% of conventional balloon angioplasty procedures.
(Enlarge Image)
Cutaway view of a coronary artery showing a stent implanted to treat a previously flow-limiting stenosis. Reproduced from Herrmann[135] with permission from the Massachusetts Medical Society.
The demonstration in the mid-1990s that coronary stenting reduced angiographic restenosis rates in large-diameter vessels from the 3040% rate seen with balloon angioplasty to 1020% primarily by eliminating elastic recoil and negative vascular remodeling heralded the present era of elective stenting. The benefits of stenting over balloon angioplasty in reducing angiographic restenosis, target vessel revascularization and clinical event rates are now well established for small-vessel, saphenous graft, and restenotic lesions, as well as for chronic coronary artery occlusion and acute myocardial infarction. Increasing use of stents for more complex lesion types (diffuse, small-vessel and bifurcated lesions) and in high-risk settings (e.g. , diabetic patients) has, however, highlighted the problem of in-stent restenosis. Two recent breakthrough technologies brachytherapy (intracoronary radiation) for the treatment of in-stent restenosis and drug-eluting stents for (primarily) the prevention of restenosis have largely resolved this issue. By allowing controlled release of antiproliferative agents directly to the injured endothelium, drug-eluting stents offer the prospect of virtually eradicating in-stent restenosis, especially of the diffuse variety. Two drug-eluting stents the sirolimus-eluting CYPHER™ stent (Cordis/Johnson & Johnson, Miami, Florida) and the paclitaxel-eluting TAXUS™ stent (Boston Scientific Corporation, Natick, Massachusetts) are currently approved in the U.S. by the Food and Drug Administration (FDA) for prevention of restenosis in native coronary arteries.
From its inception, PCI has been intended as a focal treatment of flow-limiting coronary stenosis associated with discrete culprit lesions. However, in addition to providing lasting improvement in luminal patency, the ultimate goal of percutaneous coronary revascularization is to prevent morbidity and mortality arising from ongoing atherosclerosis in nonstenotic coronary segments. Coronary atherosclerosis is a diffuse, multifocal disease process that affects the entire coronary arterial tree, and patients with acute coronary syndromes are likely to have multiple sites of coronary plaque ulceration. Recurrent ischemic events after PCI are often due to atherosclerotic disease progression at sites removed from the culprit lesion, and serial angiographic studies indicate that most myocardial infarctions occur at sites previously associated with only mild or moderate luminal stenosis. This extensive, pan-coronary deterioration in non-culprit lesions may reflect a diffuse destabilization of atherosclerotic plaques after the initial ischemic event. Moreover, plaque vulnerability and liability for ischemic events are determined more by the biological properties of the coronary plaque than by the degree of vessel stenosis. Indeed, vulnerable plaques are frequently not severely stenotic prior to rupture, as the accumulating atheroma is accommodated by positive vascular remodeling, thereby offsetting the reduction in lumen size. The detrimental effects of progressive atherosclerosis on the long-term efficacy of PCI are seen in the frequent need for repeat revascularization in patients with multivessel disease and the high ratio of new lesion-to-target lesion restenosis in those with saphenous vein grafts.
Accumulating evidence of the diffuse nature of coronary artery disease, coupled with the inherent difficulties involved in identifying and treating multiple individual lesions, underlines the importance of adjunctive systemic pharmacotherapy and risk factor modification post-PCI in stabilizing atherosclerotic plaques throughout the coronary vasculature and reducing the likelihood of further ischemic events.
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