Atherothrombosis
Peripheral Arterial Disease (PAD)

Peripheral Arterial Disease (PAD) afflicts up to 8 million people in the United States 18

PAD is atherosclerotic disease that occurs in arteries outside the heart and brain, mainly in the lower and upper extremities, kidneys, and stomach. PAD has been estimated to have a prevalence of as high as 57% in some populations. Prevalence of PAD varies from 4.3% to 57%, and depends on the diagnostic criteria used and age and risk factor distributions in the population studied. 12

Patients with large-vessel PAD experience poor circulation and face nearly 6 times the risk of death from cardiovascular disease, including myocardial infarction (MI) and stroke (within 10 years vs. individuals with no evidence of PAD). In fact, cardiovascular disease, including MI and stroke, is the major cause of death in patients with PAD. 13 16% of PAD patients experience a cardiovascular event within one year of diagnosis, and 33% of PAD patients have an atherothrombotic event within 3 years of diagnosis. Up to a 15-fold increase in cardiovascular disease and coronary heart disease-related mortality is linked with severe and symptomatic large-vessel PAD. 18

Ten-year survival curves for patients with symptomatic or asymptomatic PAD compared with normal subjects

Peripheral Arterial Disease (PAD) Ten-year Patient Survival Curve chart

Atherosclerosis is the most common cause of peripheral arterial disease. The risk of PAD increases with advancing age, male gender, history of diabetes, and smoking. 20 PAD often is asymptomatic. Researchers detected large-vessel PAD in 12% of 613 patients using the ankle-brachial index measurement, but only 20% of the diagnosed population reported symptoms. 13 When symptoms are present, intermittent claudication is one of the more common findings and is often relieved by rest. Patients typically report a cramping or fatigue in the calf, thigh, or buttock, which occurs because of the development of ischemia. 5

Common risk factors for PAD include: 3

  • Diabetes
  • Smoking
  • Hypertension
  • Hyperlipidemia
  • Advancing age 12

PAD warning signs include: 22

  • exertional pain or discomfort in buttocks, thighs, or calves
  • tingling, numbness, or skin discoloration
  • hair loss on feet or toes

Relevant Study — The REACH Registry

The REduction of Atherothrombosis for Continued Health — or REACH — Registry conducted a study of more than 69,000 patients, to identify comparable patterns in atherosclerosis risk factor prevalence. Read about the REACH Registry study.

Indications
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Use PLAVIX plus aspirin for patients with non–ST–segment elevation acute coronary syndrome (UA/non–Q–wave MI), including patients to be managed medically and those to be managed with percutaneous coronary intervention (with or without stent) or CABG, to decrease the rate of a combined end point of CV death, MI, or stroke as well as the rate of a combined end point of CV death, MI, stroke, or refractory ischemia.

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Use PLAVIX plus aspirin for patients with ST–segment elevation acute myocardial infarction to reduce the rate of death from any cause and the rate of a combined end point of death, reinfarction, or stroke. This benefit is not known to pertain to patients who receive primary angioplasty.

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Use PLAVIX alone for patients with a history of recent stroke, recent MI, or established PAD to reduce the rate of a combined end point of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.
Important Risk Information 18
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PLAVIX is contraindicated in patients with active pathologic bleeding such as peptic ulcer or intracranial hemorrhage. PLAVIX should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or coadministration with NSAIDs or warfarin. (See CONTRAINDICATIONS and PRECAUTIONS.*)

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The rates of major and minor bleeding were higher in patients treated with PLAVIX plus aspirin compared with placebo
plus aspirin in clinical trials. (See ADVERSE REACTIONS.*)

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Due to an expected reduction in drug levels and clinical efficacy, concomitant use of drugs that inhibit CYP2C19 (eg, omeprazole) should be discouraged. (See PRECAUTIONS.*)

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As part of the worldwide post–marketing experience with PLAVIX, there have been cases of reported thrombotic thrombocytopenic purpura (TTP), some with fatal outcome. TTP has been reported rarely following use of PLAVIX, sometimes after a short exposure (<2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment including plasmapheresis (plasma exchange). (See WARNINGS.*)

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Based on literature, patients with genetically reduced CYP2C19 function have diminished responses and generally exhibit higher CV event rates following MI. (See PRECAUTIONS.*)

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In clinical trials, the most common clinically important side effects were pruritus, purpura, diarrhea, and rash; infrequent events included intracranial hemorrhage (0.4%) and severe neutropenia (0.05%). (See ADVERSE REACTIONS.*)