Drug-eluting stents for the treatment of coronary artery disease

2 Clinical need and practice

2.1 Coronary artery disease is also known as coronary heart disease (CHD) and ischaemic heart disease. It is narrowing (stenosis) of the coronary arteries as a result of deposition of atherosclerotic plaque, which results in an insufficient supply of oxygen to the heart muscle. CHD may affect one or more arteries, which may be of different diameters (calibres). The stenosis of arteries may be partial or total. Coronary artery stenosis may be asymptomatic or may lead to angina – chest pain that may be severe enough to restrict or prevent exertion. A critical reduction of the blood supply to the heart may result in myocardial infarction (MI) or death.

2.2 Mortality rates from CHD are decreasing but CHD remains the most common cause of mortality in the UK. It accounted for nearly 117,500 deaths in the UK in 2002 (about 103,000 deaths in England and Wales). CHD is also the cause of considerable morbidity and loss of ability to lead a normal life. In the UK, annually, approximately 259,500 people experience an acute MI and approximately 341,500 new cases of angina (the most common form of CHD morbidity) are reported. In Europe, CHD has been estimated to account for 9.7% of total disability-adjusted life years lost.

2.3 Mortality and morbidity rates associated with CHD vary by socioeconomic group (rates are higher in lower socioeconomic groups), by geographical area (rates are highest in Wales, North West England, and the Northern England and Yorkshire regions, and lowest in South East England) and by ethnic group (for example, CHD rates are highest among people from the Indian subcontinent living in the UK). The prevalence of CHD also increases with age and is higher in men than women. The disease is more common in people with high serum cholesterol and/or high blood pressure, in people who have type 1 or type 2 diabetes mellitus, in people who smoke, and in people who are physically inactive and/or obese.

2.4 The symptoms and health risks associated with a stenosed artery may be treated medically, by modifying risk factors (for example, smoking, hyperlipidaemia, obesity and hyperglycaemia) and/or by drug treatment (for example, beta-adrenergic blockers, nitrates, calcium-channel blockers, antiplatelet agents and/or statins).

2.5 If these medical treatments fail or are inappropriate, two invasive therapies are available. The first, coronary artery bypass grafting (CABG), involves major cardiac surgery. The second, balloon angioplasty (or percutaneous transluminal coronary angioplasty) involves a widening from within the artery using a balloon catheter, which is inserted through a femoral artery. When inflated, the balloon increases the calibre of the artery. Most percutaneous transluminal coronary angioplasty procedures involve the use of stents. A stent is a thin wire-mesh tube loaded over an angioplasty balloon. When the balloon inflates, the stent expands like a scaffold to hold the vessel open, and is left behind after the balloon is deflated and withdrawn. Percutaneous coronary intervention (PCI) is a generic term that encompasses percutaneous transluminal coronary angioplasty with or without stenting. The comparison of CABG with PCI including coronary artery stents (bare-metal and drug-eluting) was covered by NICE technology appraisal guidance 71 and is not dealt with in this appraisal.

2.6 One of the criteria for comparing the clinical effectiveness of PCI with stents with standard PCI (without stents) is the incidence of subsequent attacks of angina and major adverse coronary events (MACEs), which include death, MI and the need for further revascularisation procedures (CABG or repeat PCI).

2.7 A number of problems with PCI may occur. Recoil of the artery which happens when the balloon is deflated, usually occurs immediately or within 24 hours of completing the procedure, and may be associated with acute occlusive dissection of the vessel and require emergency CABG. In the medium term restenosis of the artery after the procedure may occur and has two main causes: contraction of the outer layer of the artery secondary to an injury reaction (3–6 months after the procedure) and proliferation of smooth muscle cells within the arterial wall (4–6 months after the procedure), leading to intimal hyperplasia. As a consequence of restenosis, a repeat procedure may be required and the rate of reintervention is greater in patients who have arteries of small calibre ('small vessels' – less than 3 mm in calibre), saphenous vein grafts and long lesions (longer than 15 mm) or total occlusions. People with diabetes, who commonly have arteries affected by atherosclerosis, also have a higher rate of restenosis.

2.8 Stent technology (type and platform, including the design, alloy used and strut thickness) has developed rapidly, and recent advances aim to reduce the likelihood of restenosis. Because restenosis is correlated with the degree of inflammation present at the time of angioplasty, drug-eluting stents (DESs) were developed. These are bare-metal stents (BMSs) coated with a drug, usually an immune suppressant, to reduce inflammation or an antimitotic agent to reduce cell proliferation. The drug reaches therapeutic concentrations in local tissues only and may not be detectable systemically, thus avoiding systemic adverse effects. A subsequent development was the use of a drug–polymer mix where the drug is held temporarily in place within a polymer 'painted' onto the metallic stent, allowing the drug to elute slowly into surrounding tissues. However, not all stents are polymer based.

2.9 According to British Cardiovascular Intervention Society (BCIS) data, approximately 70,000 PCI procedures were undertaken in the UK in 2005, equating to 1165 per million of the population. In England, the number of procedures per million of the population was 1169, and in Wales, 873.

2.10 The National Service Framework for CHD set a target in March 2000 for revascularisations (PCIs and CABGs), of at least 1500 per million of the population (750 for each type of intervention).

2.11 According to BCIS data, in the UK, the proportion of PCI procedures using stents rose steeply between 1993 and 1999, from below 10% to nearly 80%. It continued to increase, although more slowly, to about 94% in 2005. Data for DES use were not available before 2002. In 2003 it was reported that 17% of all stents used in the UK were DESs. In 2005 this had risen to around 62% in the UK, 60% in England and 77% in Wales. Given the increases in numbers of PCI procedures, it may be that utilisation rates are now much higher than this.

2.12 There is a risk of stent thrombosis associated with the use of both types of stent (DESs and BMSs). To prevent thrombosis occurring, patients are required to use an antiplatelet drug, such as clopidogrel, in addition to aspirin during and after the implantation of a stent. Following data published in 2006, the US Food and Drugs Administration (FDA)'s Circulatory Devices Systems Advisory Panel recommended that the duration of clopidogrel use should be extended in patients receiving a DES. The American College of Cardiologists/American Heart Association PCI guidelines (also endorsed by the Society for Cardiovascular Angiography Interventions) and the BCIS have recommended that for patients receiving DESs the duration of clopidogrel use should be increased to at least 12 months, after which time continuation of clopidogrel should be reviewed taking into account the risk for further events on an individual patient basis.