Peripheral arterial disease aspirin

The CAPRIE trial found that compared to aspirin (325 mg daily), clopidogrel (75 mg daily) was associated with RRR of 8.7% p = 0.043) for the composite endpoint of ischemic stroke, Ml, or vascular death among 19,185 subjects with stroke, MI, or peripheral arterial disease, but no significant reduction in the composite endpoint in the subgroup with stroke (RRR 7.3%, p = 0.26). No comparison of clopidogrel with aspirin in the acute stroke period was performed. Furthermore, stroke as an endoint was not significantly reduced in the stroke patients entered in this trial (RRR 8.0%, p = NS). 

Prior to myocardial infarction, coronary artery bypass graft (CABG), peripheral artery disease, cerebrovascular accident, or aspirin use... 

A 62-year-old hypertensive man with renal artery stenosis, an adrenal adenoma, peripheral artery disease, and an abdominal aortic aneurysm developed a hypertensive crisis with chest pain. He was treated with nitrates, heparin, aspirin, and nicardipine, which were afterwards replaced by diltiazem 200 mg/day, because of persistent chest pain. He developed atrioventricular block 2 hours after the second dose of diltiazem, and was successfully treated with a pacemaker. 

The efficacy of clopidogrel as an antiplatelet agent in atherothrombotic disorders was demonstrated in the CAPRIE trial. In this study of more than 19,000 patients with a history of either myocardial infarction (MI), stroke, or peripheral arterial disease (PAD), clopidogrel 75 mg/day was compared with aspirin 325 mg/day for its ability to decrease MI, stroke, or cardiovascular death. In the final analysis, clopidogrel was slightly (8% relative risk reduction [RRR]) more effective than aspirin (p =. 043) and had a similar incidence of adverse effects. It is not associated with the blood dyscrasias (neutropenia) common with its congener, ticlopidine, and is used widely in patients with atherosclerosis. 

Data proving that antiplatelet therapies can prevent or delay the progression of peripheral arterial disease are currently unavailable. However, aspirin therapy has repeatedly been proven to significantly reduce serious vascular events in these "high-risk" patients and, in the absence of contraindications, is highly recommended. 

Ticlopidine and clopidogrel are thienopyridines, which through inhibition of platelet aggregation prolong bleeding time and delay clot retraction. The thienopyridines are prescribed for reduction of myocardial infarction and stroke, for treatment of peripheral arterial disease, and in combination with aspirin for acute coronary syndromes. This latter utility appears to result from the fact that both aspirin and the thienopyridines block major amplification pathways, leading to platelet aggregation... 

In a meta-analysis of studies of patients with peripheral arterial disease, combined use of oral anticoagulants together with aspirin increased the risk of major bleeding about twofold when compared with aspirin alone, and appeared to be associated with increased mortality. ... 

Berger, J.S., Krantz, M.J., Kittelson, J.M., Hiatt, W.R. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease A meta-analysis of randomized trials. Jama 301, 1909-1919 (2009)... 

Results of TRA 2 P-TIMI 50 trial demonstrated for the first time that a thrombin receptor (PAR-1) antagonist, when added to standard antiplatelet therapy that comprises P2Yi2 antagonist and aspirin, reduced the risk of recurrent cardiovascular events in the long-term. Vorapaxar received FDA approval in 2014 to reduce the risk of myocardial infarction, stroke, cardiovascular death, and revascularization procedures in patients who have had a heart attack or who have peripheral arterial disease. 

Antithrombotic therapy for acute peripheral occlusive disease is largely empirical. Thrombolytic therapy typically is reserved for patients in whom the occlusion is not amenable to surgery and for those in whom a possible delay between the initiation of therapy and thrombolysis would not jeopardize the viability of the limb. Evidence that antithrombotic therapy changes the natural course of the peripheral disease is sparse, but these patients are at an increased risk of cardiovascular mortality and should receive long-term aspirin therapy. Initial trials suggest that ticlopidine may improve the symptoms of chronic arteriosclerotic arterial insufficiency and also reduce fatal and nonfatal cardiovascular events, but further studies are needed. 

SchweizerJ, Kirch W, Koch R, Muller A, HellnerG, Forkmann L. Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis. Angiology 2000 51(1 I ) 913—923. 

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