Peripheral artery disease

Direct Fibrinolytics Alfimeprase is a recombinant tmncated form of fibrolase, a fibrinolytic zinc metalloproteinase isolated from the venom of the Southern copperhead snake. It degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This may result in faster recanalization and a decreased risk of hemorrhagic conversion. The initial data on the safety and efficacy of alfimeprase in peripheral arterial occlusion disease appeared very promising, but recent communication from the sponsor revealed that the phase III trials of the drug in peripheral arterial disease and catheter obstruction (NAPA-2 and SONOMA-2) failed to meet their primary and key secondary endpoints of revascularization. A trial for I AT in acute stroke (CARNEROS-1) is planned to begin soon. 

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... 

Peripheral arterial disease (claudication or ankle-brachial index less than 0.9)... 

MN is a 48-year-old man with a history of hypertension and smoking who presents to the clinic for evaluation of his cholesterol. He denies having chest pain or history of myocardial infarction, stroke, or peripheral artery disease. He has no siblings and both parents are alive with no history of CHD. MN says that he smokes about 1 pack of cigarettes per day. He does not exercise on a regular basis. He has been fasting for approximately 11 hours. 

Hung HC, Merchant A, Willett W, Ascherio A, Rosner BA, RimmEand JoshipuraKJ. 2003. The association between fruit and vegetable consumption and peripheral arterial disease. Epidemiology 14(6) 659— 665. 

The response-to-injury hypothesis states that risk factors such as oxidized LDL, mechanical injury to the endothelium, excessive homocysteine, immunologic attack, or infection-induced changes in endothelial and intimal function lead to endothelial dysfunction and a series of cellular interactions that culminate in atherosclerosis. The eventual clinical outcomes may include angina, myocardial infarction, arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death. 

The goals of treatment are to lower total and LDL cholesterol in order to reduce the risk of first or recurrent events such as myocardial infarction, angina, heart failure, ischemic stroke, or other forms of peripheral arterial disease such as carotid stenosis or abdominal aortic aneurysm. 

Goal BP values are <140/90 for most patients, but <130/80 for patients with diabetes mellitus, significant chronic kidney disease, known coronary artery disease (myocardial infarction [MI], angina), noncoronary atherosclerotic vascular disease (ischemic stroke, transient ischemic attack, peripheral arterial disease [PAD], abdominal aortic aneurysm), or a 10% or greater Framingham 10-year risk of fatal coronary heart disease or nonfatal MI. Patients with LV dysfunction have a BP goal of <120/80 mm Hg. 

In addition to coronary sclerosis, evidence is accumulating that high Lp(a) levels may be important in the development of cerebrovascular and peripheral arterial disease, as well (J6, T8, U2). Lp(a) levels not only correlated well with clinical endpoints such as transient ischemic attack and cerebral infarction, but also were associated with the extent and severity of carotid atherosclerosis, as assessed by bidirectional Doppler ultrasound (K23, M33, Z2). 

Schneider B. (1992). [Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies]. Arzneimittelforschung. 42(4) 428-36. 

It is well-established that an elevated level of cholesterol, particnlarly that carried largely in the form of LDLs, is an independent risk factor for the development of atherosclerosis and its sequelae, including coronary artery disease (leading to heart attacks), strokes, and peripheral arterial disease. 

Therapeutic applications. PG derivatives are used to induce labor or to interrupt gestation (p. 126) in the therapy of peptic ulcer (p. 168). and in peripheral arterial disease. 

Recent Ml or stroke, or established peripheral arterial d/sease For patients with a history of recent Ml, recent stroke, or established peripheral arterial disease, clopidogrel has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new Ml (fatal or not), and other vascular death. 

Recent Ml, recent stroke, or established peripheral arterial disease The recommended dose of clopidogrel is 75 mg once daily with or without food. 

Peripheral artery disease (PAD) patients usually feel leg pain when walking, which is caused by insufficient blood flow to keep up with energy demand. The P MRS data collected in a PAD patient group showed prolonged PCr recovery rate (or time constants) in the calf muscle after exhaustive exercise, suggesting the transition from anaerobic to aerobic energy metabolism is delayed due to impaired oxygen supply or mitochondria fimction caused by atherosclerosis. ... 

R. Esterhammer, M. Schocke, O. Gorny, L. Posch, H. Messner, W. Haschke, G. Praedrich and A. Greiner, Phosphocreatine kinetics in the calf muscle of patients with bilateral symptomatic peripheral arterial disease during exhaustive incremental exercise. Mol. Imaging Biol, 2008,10,30-39. 

TREATMENT OF PERIPHERAL ARTERY DISEASE AND INTERMITTENT CLAUDICATION... 

Atherosclerosis can result in ischemia of peripheral muscles just as coronary artery disease causes cardiac ischemia. Pain (claudication) occurs in skeletal muscles, especially in the legs, during exercise and disappears with rest. Although claudication is not immediately life-threatening, peripheral artery disease is associated with increased mortality, can severely limit exercise tolerance, and may be associated with chronic ischemic ulcers and susceptibility to infection. 

A number of studies have investigated the use of PGE1 and PGI2 compounds in Raynaud s phenomenon and peripheral arterial disease. However, these studies are mostly small and uncontrolled, and these therapies do not have an established place in the treatment of this disease. 

Ginkgo biloba has been studied for its effects on mild to moderate occlusive peripheral arterial disease. Randomized... 

Kim HJ, Jang SY, Park JI, Byun J, eet al. 2004. Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease. Exp Mol Med. 36 336-344. 

Nizankowski R, Krolikowski W, Bielatowicz J, Szczeklik A. Prostacyclin for ischemic ulcers in peripheral arterial disease. A random assignment, placebo controlled study. Thromb Res 1985 37(l) 21-8. 

Of 308 patients 73% had contraindications, risk factors, or intercurrent illnesses necessitating withdrawal of metformin (31) 19% had renal impairment, 25% heart failure, 6.5% respiratory insufficiency, and 1.3% hepatic impairment 51% had advanced coronary heart disease, 9.8% atrial fibrillation, 3.3% chronic alcohol abuse, 2% advanced peripheral arterial disease, and 0.7% were pregnant. 

Four fatal cases in 18 months in a community hospital were reported three had clear contraindications (32) a 45-year-old woman with liver cirrhosis, a 64-year-old man with coronary artery disease, and a 65-year-old man with peripheral arterial disease and asthma a 74-year-old man had renal insufficiency. 

PAD=peripheral arterial disease PTA=percutaneous transluminal angioplastry PTCA=DA= directional atherectomy PTCA=percutaneous transluminal coronary angioplasty. 

Tran H, Anand SS. Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. JAMA. 2004 292 1867-1874. 

Giannini D, Balbarini A. Thrombolytic therapy in peripheral arterial disease. Curr Drug Targets Cardiovasc Haematol Disord. 2004 4 249-258. 

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