Pharmacologic Management of Intermittent Claudication James B. Froehlich and John D. Bisognano Many pharmacologic agents have been studied for the medical management of intermittent claudication, there has been little success in identifying drugs that significantly alter the natural history of peripheral artery disease (PAD), and so far none has proved superior to exercise therapy. Critically important to the medical management of patients with claudication is the significant cardiac comorbidity in these patients and the need for treatment with pharmacologic agents that lessen cardiac risk. Several drugs have been shown to lessen the risk of these events and possibly improve peripheral vascular symptoms. The American College of Cardiology/American Hearth Association (ACC/AHA) Guidelines for the Management of Patients with Peripheral Arterial Disease, published in 2005, is the most comprehensive review of the epidemiology, diagnosis, and management of PAD. Nature of the Problem Ischemic intermittent claudication becomes asymptomatic when metabolic demands in exercising muscles exceed the oxygen and nutrient supply. The relative ischemia presumably elicits a maximal endogenous vasodilator response. Theoretically, numerous pharmacologic avenues can benefit patients in this setting, including augmenting vasodilation with exogenous vasodilators, altering skeletal muscle metabolic demands, enhancing blood flow by altering flow characteristics of the blood itself, and improving the endothelial dysfunction in atherosclerotic vessels. Pharmacologic therapies addressing each of these physiologic avenues have been proposed. Concomitant Coronary Artery Disease The most important aspect of pharmacologic treatment for this disease is the recognition that coronary artery disease (CAD) accompanies peripheral artery disease in the majority of patients. CAD represents the greatest cause of morbidity and mortality for these patients; estimated to be as high as 25% to 30% over 5 years in symptomatic PAD. Measures to prevent myocardial infarction (MI) are strongly indicated. In fact, it is generally agreed that patients with PAD, even without documented or known CAD, should be treated as if they had known CAD, with the same appropriate secondary prevention measures. These include routine use of antiplatelet agents, smoking cessation, aggressive treatment of diabetes, appropriate control of hypertension, and, most importantly, aggressive lipid lowering. Antiplatelet agents have specifically been shown to improve outcomes in patients with cardiovascular disease and also to improve patency of peripheral bypass grafts. However, more recent studies have called the efficacy of antiplatelet agents in the PAD population specifically into question. A meta-analysis of aspirin use in controlled trials specifically looking at PAD treatment failed to find significant reductions in cardiovascular events. However, in studies that evaluated aspirin use alone (versus in combination with dipyridamole), there was a strong trend toward reduction in total cardiovascular events (relative risk [RR], 0.75; 95% confidence interval [CI], 0.48–1.18), as well as a statistically significant reduction in stroke risk (RR, 0.64; 95% CI, 0.42–0.99). Likely, such meta-analyses suffer from being underpowered, because there are not many randomized trials of aspirin use specifically in PAD. Similarly, smoking cessation is associated with improved outcomes in peripheral vascular disease, although for obvious reasons, randomized, controlled trials do not exist. Observational studies have clearly shown an improvement in outcomes for patients with PAD and other forms of vascular disease who quit smoking over those who do not quit. Every patient seen in a vascular clinic, or by vascular specialists, should be asked about smoking status, and smokers should be offered smoking cessation therapy. Lipid-lowering therapy has been shown to decrease the incidence of MI and cardiovascular death, as well as stroke, in patients with hyperlipidemia, PAD, and CAD. More specifically, the Heart Protection Study demonstrated a 24% reduction in the endpoint of MI, MI-related death, stroke, or revascularization in all these patient groups. This was particularly evident in patients with PAD and no known CAD. Two studies even demonstrated that lipid-lowering with statin therapy lessened claudication symptoms as well. Rheologic Agents For many years the only FDA-approved medication for the treatment of claudication was pentoxifylline. This agent is thought to increase red blood cell pliability and thereby decrease blood viscosity. Data also suggest that it can increase smooth muscle cell relaxation and inhibit platelet aggregation. All of these effects would be of theoretical advantage in the setting of PAD-related claudication. A meta-analysis of all pentoxifylline studies showed an improvement in pain-free walking distance and total walking distance with pentoxifylline compared with placebo; the improvement achieved statistical significance, but the difference was very small. This finding was of unclear clinical significance and was much smaller than that seen with exercise therapy. Furthermore, the minimal increase in claudication distance is inconsequential in most patients. For these reasons, pentoxifylline is not usually recommended for the treatment of claudication. Only gold members can continue reading. 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Pharmacologic Management of Intermittent Claudication James B. Froehlich and John D. Bisognano Many pharmacologic agents have been studied for the medical management of intermittent claudication, there has been little success in identifying drugs that significantly alter the natural history of peripheral artery disease (PAD), and so far none has proved superior to exercise therapy. Critically important to the medical management of patients with claudication is the significant cardiac comorbidity in these patients and the need for treatment with pharmacologic agents that lessen cardiac risk. Several drugs have been shown to lessen the risk of these events and possibly improve peripheral vascular symptoms. The American College of Cardiology/American Hearth Association (ACC/AHA) Guidelines for the Management of Patients with Peripheral Arterial Disease, published in 2005, is the most comprehensive review of the epidemiology, diagnosis, and management of PAD. Nature of the Problem Ischemic intermittent claudication becomes asymptomatic when metabolic demands in exercising muscles exceed the oxygen and nutrient supply. The relative ischemia presumably elicits a maximal endogenous vasodilator response. Theoretically, numerous pharmacologic avenues can benefit patients in this setting, including augmenting vasodilation with exogenous vasodilators, altering skeletal muscle metabolic demands, enhancing blood flow by altering flow characteristics of the blood itself, and improving the endothelial dysfunction in atherosclerotic vessels. Pharmacologic therapies addressing each of these physiologic avenues have been proposed. Concomitant Coronary Artery Disease The most important aspect of pharmacologic treatment for this disease is the recognition that coronary artery disease (CAD) accompanies peripheral artery disease in the majority of patients. CAD represents the greatest cause of morbidity and mortality for these patients; estimated to be as high as 25% to 30% over 5 years in symptomatic PAD. Measures to prevent myocardial infarction (MI) are strongly indicated. In fact, it is generally agreed that patients with PAD, even without documented or known CAD, should be treated as if they had known CAD, with the same appropriate secondary prevention measures. These include routine use of antiplatelet agents, smoking cessation, aggressive treatment of diabetes, appropriate control of hypertension, and, most importantly, aggressive lipid lowering. Antiplatelet agents have specifically been shown to improve outcomes in patients with cardiovascular disease and also to improve patency of peripheral bypass grafts. However, more recent studies have called the efficacy of antiplatelet agents in the PAD population specifically into question. A meta-analysis of aspirin use in controlled trials specifically looking at PAD treatment failed to find significant reductions in cardiovascular events. However, in studies that evaluated aspirin use alone (versus in combination with dipyridamole), there was a strong trend toward reduction in total cardiovascular events (relative risk [RR], 0.75; 95% confidence interval [CI], 0.48–1.18), as well as a statistically significant reduction in stroke risk (RR, 0.64; 95% CI, 0.42–0.99). Likely, such meta-analyses suffer from being underpowered, because there are not many randomized trials of aspirin use specifically in PAD. Similarly, smoking cessation is associated with improved outcomes in peripheral vascular disease, although for obvious reasons, randomized, controlled trials do not exist. Observational studies have clearly shown an improvement in outcomes for patients with PAD and other forms of vascular disease who quit smoking over those who do not quit. Every patient seen in a vascular clinic, or by vascular specialists, should be asked about smoking status, and smokers should be offered smoking cessation therapy. Lipid-lowering therapy has been shown to decrease the incidence of MI and cardiovascular death, as well as stroke, in patients with hyperlipidemia, PAD, and CAD. More specifically, the Heart Protection Study demonstrated a 24% reduction in the endpoint of MI, MI-related death, stroke, or revascularization in all these patient groups. This was particularly evident in patients with PAD and no known CAD. Two studies even demonstrated that lipid-lowering with statin therapy lessened claudication symptoms as well. Rheologic Agents For many years the only FDA-approved medication for the treatment of claudication was pentoxifylline. This agent is thought to increase red blood cell pliability and thereby decrease blood viscosity. Data also suggest that it can increase smooth muscle cell relaxation and inhibit platelet aggregation. All of these effects would be of theoretical advantage in the setting of PAD-related claudication. A meta-analysis of all pentoxifylline studies showed an improvement in pain-free walking distance and total walking distance with pentoxifylline compared with placebo; the improvement achieved statistical significance, but the difference was very small. This finding was of unclear clinical significance and was much smaller than that seen with exercise therapy. Furthermore, the minimal increase in claudication distance is inconsequential in most patients. For these reasons, pentoxifylline is not usually recommended for the treatment of claudication. Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Technical Aspects of Percutaneous Carotid Angioplasty and Stenting for Arteriosclerotic Disease In-Situ Treatment of Aortic Graft Infection with Prosthetic Grafts and Allografts Treatment of Acute Upper Extremity Venous Occlusion Intraoperative Assessment of the Technical Adequacy of Carotid Endarterectomy Stay updated, free articles. Join our Telegram channel Join
