Peripheral artery disease and

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. 

TREATMENT OF PERIPHERAL ARTERY DISEASE AND INTERMITTENT CLAUDICATION... 

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. 

Endothelial progenitor cells can be sorted from the peripheral blood of patients with peripheral artery diseases and can be implanted into ischemic limbs in order to increase collateral vessel formation and to secrete various angiogenic factors or cytokines, Although this novel angiogenic cell therapy seems to be feasible, remote angiogenic actions should be considered as possible side effects, and the clinical efficacy should be tested by specific studies (79-81). 

Khan E Litchfield SJ, Belch JJ. Cutaneous microvascular responses are improved after cholesterol-lowering in patients with peripheral arterial disease and hypercholesterolaemia. Adv Exp Med Biol 1997 428 49-54. 

A 90-year-old man with a history of peripheral arterial disease and mild heart failure presented with reduced appetite, insomnia, anhedonia, reduced energy, and suicidal ideation. His symptoms had started a month before, when he had begun to take quinapril 10 mg/ day. He was also taking furosemide 20 mg/day and digoxin. He was alert, coherent, and cognitively intact, but depressed with a flat affect. He had no psychotic symptoms. Quinapril was withdrawn. He improved within 48 hours and recovered fully in 5 days. 

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. 

Atenolol, betaxolol, bisoprolol, and metoprolol are cardioselective /3 -blockers. Therefore, they are safer than nonselective fi -blockers in patients with asthma, COPD, peripheral arterial disease, and diabetes who have a compeUing indication for a /6-blocker. However, cardioselectivity is a dose-dependent phenomenon. At higher doses, cardioselective agents lose their relative selectivity for /6i-receptors and block /32-receptors as effectively as they block /6i-receptors. The dose at which cardioselectivity is lost varies from patient to patient. In general, cardioselective /6-blockers are preferred when using a /3-blocker to treat hypertension. 

Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med 2001 344 1608-1621. 

Hutter C, Austin M, Humphries S. Familial hypercholesterolemia, peripheral arterial disease, and stroke A HuGE minireview. Amer J Epidemiol 2004 160 430 35. 

Hiatt WR. Pharmacologic therapy for peripheral arterial disease and claudication. J Vase Surg 2002 36 1283-1291. 

Optrin has demonstrated a reduction of atherosclerosis by eliminating inflammatory cells and is actually in Phase II studies for the primary treatment of peripheral artery disease and for the prevention of restenosis following angioplasty [71]. 

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... 

Ticlopidine (29) is equally effective in both men and woman and also improves symptoms of claudication in patients with peripheral arterial disease and appears to reduce anginal pain. Patients with subarchnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. 

Key contraindications include congestive heart failure (New York Heart Association class II-IV), inadequately controlled hypertension with persistent BP elevation >140/90 mmHg, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease, active peptic ulceration or GI bleeding, creatinine clearance <30 mL/min, or severe hepatic dysfunction [4],... 

Melian, EB and Goa, KL (2002) Beraprost a review of its pharmacology and therapeutic efficacy in the treatment of peripheral arterial disease and pulmonary arterial hypertension. Drugs, 62, 107-133. 

Siitonen O, VusitupaM, Pyorala K, Voutilainen E, Lansimies E. Peripheral arterial disease and its relationship to cardiovascular risk factors and coronary artery disease in newly diagnosed non-insuUn dependent diabetes mellitus. Act Med Scand 1986 220 205-212. 

Lowe GD, Fowkes FG, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen and activation of coagulation and leucocyte in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation 1993 87 1915-1920. 

Clearly, diabetics who have peripheral arterial disease have higher mortality rates than those who do not have arterial disease. A recent study by Vogt et al. (15) evaluated the relationship between peripheral arterial disease and mortality in a population of close to 2000 individuals over a 13-year period. All patients 50 years of age and older with no history of lower extremity surgery were evaluated for the presence of peripheral arterial disease. Analysis of the data stratified by populations and comorbid conditions showed that a low ankle-brachial index is an independent predictor of all causes of mortality in both men and women with peripheral arterial disease. This increase is a relative risk and is unchanged after exclusions of all patients with a clinical history of cardiovascular disease or diabetes. Thus, a low ankle-brachial index is an important measurement to obtain to assess the risk of mortality among those who smoke and have either angina or diabetes. 

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