Antiplatelet therapy in peripheral arterial disease

Antiplatelet therapy significantly reduces the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with peripheral arterial disease (PAD) and intermittent claudication, in patients undergoing peripheral grafting, in patients undergoing peripheral angioplasty, and in patients with carotid disease. Aspirin, aspirin plus dipyridamole, ticlodipine, and clopidogrel have been shown to be efficacious in the treatment of PAD. Data from the Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events (CAPRIE) trial demonstrated in 11,592 patients with PAD that patients randomized to clopidogrel 75 mg daily had a 24% significant (p=0.0028) reduction in vascular death, nonfatal myocardial infarction, and nonfatal stroke than patients randomized to aspirin 325 mg daily. These data favor the use of clopidogrel in patients with PAD.     

Antioxidants in peripheral arterial disease

Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis that is characterized by obstruction of the arteries in the lower limbs. Experimental and epidemiological studies suggest a key role for oxidative stress in initiation and progression of the atherosclerotic process. The results of these studies provided a good basis for interventional trials with antioxidants, particularly with vitamin E, but the findings were conflicting. In this paper we review the observational and interventional studies with antioxidants, and ask whether vitamin supplementation should be recommended for PAD patients.     

Hypertension in peripheral arterial disease

Peripheral arterial disease (PAD) of the lower limbs is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PAD, but is in its own value an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two-to-five fold. Hypertension is a risk factor for vascular disorders, including PAD. Of hypertensives at presentation, about 2-5% have intermittent claudication, with increasing prevalence with age. Otherwise, 35-55% of patients with PAD at presentation also show hypertension. Patients who suffer from hypertension with PAD have a greatly increased risk of myocardial infarction and stroke. There is no consensus on the specific treatment of hypertension in PAD because of the limited controlled studies on antihypertensive therapy in such specific PAD population. There is an obvious need of such outcome studies, especially since the two conditions are frequently encountered together. However, as risk is high in all PAD patients, the most important goal remains to decrease the global cardiovascular risk in such patients rather than to focus on the control of blood pressure only and on the reduction of symptoms of PAD. Therefore, treatment with antiplatelet drugs, ACE-inhibitors and statins should be considered.     

Antioxidants in peripheral arterial disease

Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis that is characterized by obstruction of the arteries in the lower limbs. Experimental and epidemiological studies suggested a key role for oxidative stress in initiation and progression of the atherosclerotic process. The results of these studies provided a good basis for interventional trials with antioxidants, particularly with vitamin E, but the findings were conflicting. In this paper we review the observational and interventional studies with antioxidants, and ask whether vitamins supplementation should or should be not be recommended for PAD patients.     

Imaging stem cell therapy for the treatment of peripheral arterial disease

Arteriosclerotic cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Therapeutic angiogenesis aims to treat ischemic myocardial and peripheral tissues by delivery of recombinant proteins, genes, or cells to promote neoangiogenesis. Concerns regarding the safety, side effects, and efficacy of protein and gene transfer studies have led to the development of cell-based therapies as alternative approaches to induce vascular regeneration and to improve function of damaged tissue. Cell-based therapies may be improved by the application of imaging technologies that allow investigators to track the location, engraftment, and survival of the administered cell population. The past decade of investigations has produced promising clinical data regarding cell therapy, but design of trials and evaluation of treatments stand to be improved by emerging insight from imaging studies. Here, we provide an overview of pre-clinical and clinical experience using cell-based therapies to promote vascular regeneration in the treatment of peripheral arterial disease. We also review four major imaging modalities and underscore the importance of in vivo analysis of cell fate for a full understanding of functional outcomes.     

Emerging drugs in peripheral arterial disease

Peripheral arterial disease (PAD) is the manifestation of atherosclerotic occlusion within a peripheral vascular bed. This can occur in any noncoronary arterial bed, but PAD most commonly refers to atherosclerosis in the aorto-iliac system and infrainguinal vessels that lead to symptoms in the lower extremities. The disease most often becomes clinically apparent in elderly individuals, commonly presenting as intermittent claudication. More advanced, or multisegmental disease, may present with ischaemic rest pain or tissue loss. Although the limb manifestations of PAD can be disabling, PAD is also a marker of coronary or cerebrovascular atherosclerosis. In fact, approximately 80% of mortality in PAD patients is secondary to a cardiovascular event. In accordance with this, initial medical management of this disease focuses on preventative and risk reduction strategies to minimise the risk of cardiovascular morbidity and mortality. At present, the majority of recommendations with respect to risk reduction therapy in PAD patients are extrapolated from the coronary and cerebrovascular literature. Limb-directed therapy in PAD intends to minimise symptoms and serve as an adjunct to surgical intervention. However, existing data on the efficacy of these agents suggests that they are only partially effective. In addition, the effect of existing nonoperative intervention on the progression of disease has not been completely elucidated. As such, new therapies are under development, which target various goals, including minimising local progression of disease, minimising disability, reducing systemic cardiovascular morbidity/mortality and augmenting the durability of surgical intervention.     

Emerging drugs in peripheral arterial disease

Peripheral arterial disease (PAD) is the manifestation of atherosclerotic occlusion within a peripheral vascular bed. This can occur in any noncoronary arterial bed, but PAD most commonly refers to atherosclerosis in the aorto–iliac system and infrainguinal vessels that lead to symptoms in the lower extremities. The disease most often becomes clinically apparent in elderly individuals, commonly presenting as intermittent claudication. More advanced, or multisegmental disease, may present with ischaemic rest pain or tissue loss. Although the limb manifestations of PAD can be disabling, PAD is also a marker of coronary or cerebrovascular atherosclerosis. In fact, ~ 80% of mortality in PAD patients is secondary to a cardiovascular event. In accordance with this, initial medical management of this disease focuses on preventative and risk reduction strategies to minimise the risk of cardiovascular morbidity and mortality. At present, the majority of recommendations with respect to risk reduction therapy in PAD patients are extrapolated from the coronary and cerebrovascular literature. Limb-directed therapy in PAD intends to minimise symptoms and serve as an adjunct to surgical intervention. However, existing data on the efficacy of these agents suggests that they are only partially effective. In addition, the effect of existing nonoperative intervention on the progression of disease has not been completely elucidated. As such, new therapies are under development, which target various goals, including minimising local progression of disease, minimising disability, reducing systemic cardiovascular morbidity/mortality and augmenting the durability of surgical intervention.     

Cilostazol and peripheral arterial disease

Peripheral arterial disease is both common and disabling. Contemporary management of peripheral arterial disease is multimodal, encompassing both medical and interventional treatments. Cilostazol (Pletal^?), a 2-oxoquinolone derivative, is currently licensed in the UK for the treatment of patients with intermittent claudication to improve their walking distance in the absence of tissue necrosis or rest pain. The therapeutic effects of cilostazol are thought to be mediated through antiplatelet, antiproliferative and vasodilatory activities. This review aims to provide an overview of the management of peripheral arterial disease focusing upon cilostazol pharmacotherapy.     

Cilostazol and peripheral arterial disease

Peripheral arterial disease is both common and disabling. Contemporary management of peripheral arterial disease is multimodal, encompassing both medical and interventional treatments. Cilostazol (Pletal), a 2-oxoquinolone derivative, is currently licensed in the UK for the treatment of patients with intermittent claudication to improve their walking distance in the absence of tissue necrosis or rest pain. The therapeutic effects of cilostazol are thought to be mediated through antiplatelet, antiproliferative and vasodilatory activities. This review aims to provide an overview of the management of peripheral arterial disease focusing upon cilostazol pharmacotherapy.     

Managing peripheral arterial disease in primary care

In the UK, around 5% of people aged 55-74 years have intermittent leg pain on walking (claudication), a characteristic feature of peripheral arterial disease. The fact that their disease is symptomatic puts such individuals at high risk of experiencing serious cardiovascular complications. Yet many of them do not receive adequate secondary prevention advice and therapy. Here, we review the management of peripheral arterial disease in primary care, concentrating on those with clinically overt disease.     

Lipid management and peripheral arterial disease

Peripheral arterial disease (PAD) is a common disorder usually associated with silent or symptomatic arterial disease elsewhere in the circulation and a "cluster" of cardiovascular risk factors (e.g. smoking, dyslipidemia, hypertension, and insulin resistance/diabetes mellitus). The medical management of PAD should focus on both the relief of symptoms and prevention of secondary cardiovascular complications. This approach must include smoking cessation, optimal cholesterol levels, blood pressure and glycemic control as well as prescribing antiplatelet therapy. This review focuses on the evidence supporting the use of lipid-lowering drugs in PAD. Several trials indicate that getting low density lipoprotein-cholesterol levels to target (<2.6 mmol/l; 100 mg/dl), or even lower, is associated with improvement of symptoms and a reduction in vascular events in patients with PAD.     

Treatment of chronic peripheral arterial disease

Peripheral arterial disease (PAD) is a common but under-recognized problem. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient is presented with limb-threatening ischemia. Importantly, PAD is a marker of generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The primary causes of death in patients with PAD are myocardial infarction and stroke. Reducing risk factors is an integral and aggressive part of the treatment regimen. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication. augment functional performance, and improve quality of life. This review focuses on the general medical management and specific therapeutic options. Because PAD is a manifestation of generalized atherosclerosis, the principal issue in medical management of PAD is a treatment plan that modifies known risk factors for atherosclerosis and its atherothrombotic complications. All patients with PAD should be receiving antiplatelet therapy to prevent ischemic events and ACE inhibitors should be used if appropriate. Medical treatment for patients with claudication includes exercise in rehabilitation and drug therapy. It is also recognized that selected patients with claudication symptoms may benefit from catheter-based interventions, and most PAD patients with critical leg ischemia require revascularization procedures. Although many therapies for claudication have been thoroughly investigated, research continues on new treatments. In contrast, more prospective, randomized trials are needed to evaluate various therapies for treating patients with PAD.     

Cardiovascular morbidity and mortality in peripheral arterial disease

The term peripheral arterial disease (PAD) is often used to describe atherosclerosis involving the arteries supplying the lower extremities. Potentially modifiable factors that predispose to the development and progression of both symptomatic and asymptomatic PAD include smoking, diabetes mellitus, hyperlipidemia, and hypertension. Since the same risk factors for PAD predispose to the development of systemic atherosclerosis, identification of PAD increases the likelihood of coexistent coronary heart and cerebrovascular disease. Even after adjustment for risk factors, PAD appears to increase the risk for ischemic manifestations involving these other vascular territories with about a 2-fold increase in myocardial infarction and perhaps stroke. The most dramatic consequence of PAD is impaired survival with a 2- to 3-fold increased risk of 5- to 10-year mortality. While the adverse cardiovascular and cerebrovascular complications are highest for persons with more severe PAD, there is still a significant risk in persons with mild and even asymptomatic disease. The focus in the management of PAD should be on early diagnosis and efforts to reduce the risk of adverse events including risk factor modification and antiplatelet therapy.     

外周动脉闭塞性疾病的抗血小板与抗凝治疗进展

目的:探讨外周动脉闭塞性疾病抗血小板与抗凝治疗及进展。方法:查询近几年国内外关于外周动脉闭塞性疾病抗血小板和抗凝药物治疗文献并进行分析。结果和结论:抗血小板治疗有助于降低外周动脉闭塞性疾病患者心脑血管事件发生率,并通过提高血管重建术后的通畅率,改善患者的预后。抗凝药物在外周动脉闭塞性疾病患者的治疗中仍应占有一席之地,尤其是在某些特定情况下。抗凝和抗血小板药物合理的联用可能为外周动脉闭塞性疾病患者的药物治疗提供新的思路。