Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events

Occlusive vascular events include ischaemic stroke, transient ischaemic attack and myocardial infarction. They occur when blood flow is impeded because an artery is blocked or restricted because of atherosclerosis and atherothrombosis. Atherosclerotic plaques form in artery walls because of damage to the vascular endothelium. Damage is caused by a number of factors working together over a long period, such as elevated low-density lipoproteins, smoking, high blood pressure and diabetes mellitus. If an atherosclerotic plaque is suddenly disrupted, platelet activation and thrombus (clot) formation follows, leading to atherothrombosis. The thrombus can block an artery, either at the original site of the plaque formation or further down the artery. People who have had an occlusive vascular event are at increased risk of another.

Peripheral arterial disease is a condition in which the arteries that carry blood to the arms or legs become narrowed or clogged, slowing or stopping the flow of blood. It occurs most often because of atherosclerosis. People who have peripheral arterial disease are at high risk of having an occlusive vascular event. People with cardiovascular disease who have disease in more than 1 vascular site are said to have multivascular disease. These people are at increased risk of death, myocardial infarction or stroke, compared with people with disease in a single vascular bed.

Each year in the UK an estimated 98,000 people have a first ischaemic stroke, between 46,000 and 65,000 people have a transient ischaemic attack, and 146,000 have a myocardial infarction. Approximately 2% of the population of England and Wales have had a stroke and about 70% of all strokes are ischaemic. In the UK, in total around 510,000 people have had a transient ischaemic attack and over 1.4 million have had a myocardial infarction. About 20% of the UK population aged 55 to 75 years have evidence of lower extremity peripheral arterial disease, equating to a prevalence of 850,000 people, of whom 5% have symptoms. An estimated 16% of people with cardiovascular disease have multivascular disease.

Ischaemic stroke and myocardial infarction are associated with high mortality rates. Approximately 23% of people die within 30 days of having a stroke, and of the people who survive, 60% to 70% die within 3 years. Thirty per cent of people die from their first myocardial infarction. In terms of morbidity, an occlusive vascular event can lead to a stay in hospital, reduced health-related quality of life and long-term disability, with a resulting impact on caregivers. Stroke is the leading cause of disability in the UK and it is thought that more than 900,000 people in England are living with the effects of stroke, with about half dependent on others for support with everyday activities.

The aim of treatment is to prevent occlusive vascular events, and their recurrence. This can include pharmacological therapy with 1 or more antiplatelet agents. Antiplatelet agents include aspirin, clopidogrel and modified-release dipyridamole.

For people who have had a non-ST-segment-elevation myocardial infarction (NSTEMI), NICE's previous guideline on unstable angina and NSTEMI (now replaced by NICE's guideline on acute coronary syndromes) recommended that aspirin should be started and continued indefinitely, unless contraindicated. In people with predicted 6-month mortality greater than 1.5%, clopidogrel should be considered in addition to aspirin, unless contraindicated, and continued for 12 months. For people who have had an ST-segment-elevation myocardial infarction (STEMI), NICE's previous guideline on MI: secondary prevention (now replaced by NICE's guideline on acute coronary syndromes) recommended that patients treated with a combination of aspirin and clopidogrel during the first 24 hours after the myocardial infarction should continue this treatment for at least 4 weeks. Thereafter, standard treatment including low-dose aspirin should be given, unless there are other indications to continue dual antiplatelet therapy.

The 'National service framework for coronary heart disease' states that GPs and primary care trusts should identify all people with established cardiovascular disease and offer them comprehensive advice and appropriate treatment to reduce their risk of recurrent occlusive vascular events. GP contracts include points for the number of people with coronary heart disease or who have had a stroke and who are taking antiplatelet therapy for secondary prevention.