Coronary atherosclerotic disease remains the leading cause of mortality in the industrialized world. One American dies from coronary heart disease (CHD) every minute, with an estimated 1.2 million MIs occurring annually in the United States.1 With the epidemic of obesity in this country and Americans' increasingly sedentary lifestyle, more patients are at risk of developing CHD than ever before. Additionally, more patients are developing abnormal lipid profiles at younger ages, including elevated LDL and decreased HDL cholesterol levels. Abnormal lipid profiles are a well-documented risk factor for the development of atherosclerosis. The coupling of abnormal lipid profiles with vascular injury promotes atherosclerosis, causing symptomatic CHD, including angina pectoris and MI. When symptoms can no longer be medically managed, more invasive options, including percutaneous intervention (PCI) and coronary artery bypass grafting (CABG), may be advised. This article reviews the factors leading to development of CHD and the evolution of PCI technology, discusses how to identify which patients are the best candidates for drugeluting stent (DES) implantation, and explains how to maintain patient safety after PCI.
HOW ATHEROSCLEROSIS DEVELOPS
CHD results when neointimal injury occurs in one of the coronary arteries. Increased blood flow to this area of injury launches an inflammatory process, causing the migration of lipid-laden macrophages. Those macrophages preferentially incorporate LDL into their cells as they form a subendothelial “fatty streak.” Macrophages work in a pro-inflammatory manner by recruiting smooth-muscle cells from the tunica media, thus attracting and stimulating more macrophages. Numerous chemical mediators, including cytokines and adhesion molecules, are produced, attracting smooth muscle, connective tissue, and more lipids. The result of this inflammatory process is the formation of a fibrous plaque. This lesion grows with time until the lumen narrows, producing symptomatic CHD. When complete lumen occlusion occurs, ischemia of the myocardium results. At this point in the process, we, as practitioners, have failed to prevent morbidity from our patients' cardiovascular disease and must consider more invasive options than medical management, including PCI with stent (PCI-S) placement.
TREATMENT APPROACHES
Treatment of patients with CHD starts with risk factor identification and modification. Risk factors for CHD include positive family history, male gender, blood lipid abnormalities, diabetes mellitus, hypertension, physical inactivity, obesity, and cigarette smoking. Most MIs are attributable to eight modifiable risk factors: abnormal lipids, smoking, hypertension, diabetes mellitus, abdominal obesity, psychosocial factors, consumption of too few fruits and vegetables and too much alcohol, and lack of regular physical activity.2 Reducing patient risk for CHD is a necessity in clinical practice, but despite our best efforts at lowering risk, some patients will require pharmacologic therapy, including metformin and sulfonylureas for improved glycemic control, beta-blockers and calcium channel blockers for BP control, and statins and fibrates for patients with abnormal lipid profiles. Even then, a number of patients will become the next victims of CHD. Thus, PCI is still a much-needed and much-valued therapeutic modality.
PERCUTANEOUS INTERVENTION
When pharmacologic measures fail to control patients' CHD, PCI is the next treatment option. In the 1970s, percutaneous coronary angioplasty (PTCA) with an inflatable balloon became the newest modality for restoring luminal diameter to stenotic coronary arteries. In 1986, PTCA started losing popularity and bare-metal stent (BMS) use exploded. Initially PCI-S was heralded because it reduced the incidence of death and MI in patients presenting with acute coronary syndromes.3 BMS improved stenotic coronary artery diameter by more than 41% and routinely decreased clinical angina.4 This trend of using BMS to reduce stenosis and restore coronary blood flow to ischemic areas continued into the 1990s. However, restenosis became the Achilles' heel of BMS, occurring in 15% to 50% of all cases.2 Restenosis of BMS, which results from vascular injury, underlying atherosclerosis, and inflammation, is furthered by neointimal hyperplasia after stent deployment. This can lead to acute or gradual loss of lumen diameter. The addition of pharmacologic antiplatelet and anti-inflammatory treatment after BMS implantation reduced this side effect, but the cardiology community continued its investigation into other PCI modalities with improved efficacy. As a result of BMS restenosis, targetvessel and target-lesion revascularization became necessary in 30% to 50% of patients, dictating the need for a more effective intervention.5
The 1990s marked the arrival of the DES. The basic design includes three principal components: a stent backbone, the pharmacologic agent to reduce neointimal hyperplasia, and a polymer responsible for the slow release of the pharmacologic agent (Figure 1). As the metal stent itself is inherently thrombogenic, therapeutic agents have been investigated to limit this particular property. Paclitaxel, a chemotherapeutic agent, and sirolimus, an immunosuppressant, are the leading pharmacologic agents for DES. Paclitaxel and sirolimus have reduced rates of restenosis to 2.1% and 7%, respectively.6,7 The use of DES yields similar long-term survival benefits with less morbidity in patients with severe left ventricular dysfunction when compared with CABG.6 Patients receiving DES also have lower rates of subsequent revascularization and angina.3
In light of these dramatic improvements in patient outcomes, DES became the default PCI of choice from the late 1990s into the 21st century—until a literal fatal flaw was discovered. One of the main improvements of DES over BMS was the addition of powerful antirestenotic agents that decreased the hyperplasia seen with BMS. According to an FDA Circulatory System Devices Advisory Panel meeting in December 2006, on-label use of DES reduces the need for repeated revascularizations for 3 or more years during which time no increase in mortality rates or MIs was seen.8 However, thrombosis occurred more frequently in DES patients compared with BMS patients, 1% to 2% versus 0.4%, respectively. Although rare, thrombosis is associated with increased morbidity, including acute MI, and mortality.
Thrombosis occurs when the inherently thrombogenic metal DES does not achieve full endothelialization. This failure results in vascular injury, which initiates the clotting cascade, platelet activation, and platelet aggregation and leads to acute thrombosis of the entire lumen. The rate of thrombosis occurrence is low in the first 6 weeks after DES implantation, but an increasing number of studies document thrombus formation as late as 24 months after the procedure.7,9 In fact, data indicate that the annual incidence of stent thrombosis in DES, initially 0.6%, steadily increases over time, with a documented 2.9% incidence in 3 years.9 This trend has caused a decline in DES use from 80% in 2004 to less than 50% at present.