cardiovascular disorders
Peripheral Arterial Disease
Treatment of Peripheral Arterial Disease
Risk factor modification Exercise Antiplatelet drugs Sometimespentoxifyllineorcilostazolfor claudication Angiotensin-converting enzyme (ACE) inhibitors Percutaneous transluminal angioplasty (PTA) or surgery for severe disease All patients require aggressiverisk factor modificationfor relief of peripheral arterial disease symptoms and prevention of cardiovascular disease (CVD), including Smoking Cessation , which is essential Control of diabetes, dyslipidemia, and hypertension Structured exercise therapy Dietary changes are given to reduce the risk of CVD (see Diet ). A randomized, placebo-controlled trial showed that low-dose Beta-blockers are safe unless PAD is very severe ( Treatment references ). Exercise—35 to 50 minutes of treadmill or track walking in an exercise-rest-exercise pattern 3 to 4 times a week—is an important but underused treatment. Supervised exercise programs are probably superior to unsupervised programs. Exercise can increase symptom-free walking distance and improve quality of life. Mechanisms probably include increased collateral circulation, improved endothelial function with microvascular vasodilation, decreased blood viscosity, improved red blood cell filterability, decreased ischemia-induced inflammation, and improved oxygen extraction. Patients are advised to keep the legs below heart level. For pain relief at night, the head of the bed can be elevated about 10 to 15 cm (4 to 6 inches) to improve blood flow to the feet. Patients are also advised to avoid cold and drugs (eg,cocaine, amphetamines) or medications (eg,pseudoephedrine, contained in many sinus and cold remedies) that cause vasoconstriction. is crucial, especially for patients with diabetes. It includes daily foot inspection for injuries and lesions; treatment of calluses and corns by a podiatrist; daily washing of the feet in lukewarm water with mild soap, followed by gentle, thorough drying; and avoidance of thermal, chemical, and mechanical injury, especially that due to poorly fitting footwear. Direct wound care is discussed elsewhere. Antiplatelet Drugs may modestly lessen symptoms and increase walking distance in patients with peripheral arterial disease; more importantly, these drugs modify atherogenesis and help prevent acute coronary syndromes and transient ischemic attacks. Options for patients with symptomatic PAD include For relief of claudication,pentoxifylline400 mg orally 3 times a day with meals orcilostazol100 mg orally twice a day may be used to relieve intermittent claudication by improving blood flow and enhancing tissue oxygenation in affected areas; however, neitherpentoxifyllinenorcilostazolis a substitute for risk factor modification and exercise. Use ofpentoxifyllineis controversial because evidence of its effectiveness is mixed. A trial of≥2 months may be warranted because adverse effects are uncommon and mild. The most common adverse effects ofcilostazolare headache and diarrhea.Cilostazolis contraindicated in patients with severe heart failure. receptor blockers (ARBs) have several beneficial effects. They are antiatherogenic and are potent vasodilators. Among patients undergoing vascular intervention for chronic limb-threatening ischemia, those on ACE inhibitors or ARBs had improved amputation-free and overall survival ( Treatment references ). Other drugs that may relieve claudication are being studied; they include L-arginine(the precursor of endothelium-dependent vasodilator), nitric oxide, vasodilator prostaglandins, and angiogenic growth factors (eg, vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF]). In patients with severe limb ischemia, long-term parenteral use of vasodilator prostaglandins may decrease pain and facilitate ulcer healing. PTA with or without stent insertion is the primary nonsurgical method for dilating vascular occlusions. PTA with stent insertion may keep the artery open better than balloon compression alone, with a lower rate of reocclusion. Stents work best in large arteries with high flow (iliac and renal); they are less useful for smaller arteries and for long occlusions. Indications for PTAare similar to those for surgery: Intermittent claudication that inhibits daily activities and does not respond to risk factor modification and noninvasive treatments Rest pain Gangrene Suitable lesions are flow-limiting, short iliac stenoses (<3 cm) and short, single or multiple stenoses of the superficial femoropopliteal segment. Complete occlusions (up to 10 or 12 cm long) of the superficial femoral artery can be successfully dilated, but results are better for occlusions≤5 cm. PTA is also useful for localized iliac stenosis proximal to a bypass of the femoropopliteal artery. PTA is less useful for diffuse disease, long occlusions, and eccentric calcified plaques. Such lesions are particularly common in patients with diabetes, often affecting small arteries. Complications of PTA include thrombosis at the site of dilation, distal embolization, intimal dissection with occlusion by a flap, and complications related toheparinuse. With appropriate patient selection, PTA for iliac, thigh, and calf artery stenosis has a high success rate. A systematic review and meta-analysis documented a limb salvage rate of 95% after 12 months, target lesion revascularization rate of 14 to 25%, and a survival rate of 90% ( Treatment references ). However, the restenosis rate was 33 to 62%; repeat PTA may be successful. Surgery is indicated for patients Who can safely tolerate a major vascular procedure With severe symptoms that do not respond to noninvasive treatments The goal is to relieve symptoms, heal ulcers, and avoid amputation. Because many patients have underlying coronary artery disease, which places them at risk of acute coronary syndromes during surgical procedures for PAD, patients usually undergo cardiac evaluation prior to surgery. Thromboendarterectomy(surgical removal of an occlusive lesion) is used for short, localized lesions in the aortoiliac, common femoral, or deep femoral arteries. Revascularization(eg, femoropopliteal bypass grafting) uses synthetic or natural materials (often the saphenous or another vein) to bypass occlusive lesions. Revascularization helps prevent limb amputation and relieve claudication. Sympathectomymay be effective in patients who cannot undergo major vascular surgery, when a distal occlusion causes severe ischemic pain. Chemical sympathetic blocks are as effective as surgical sympathectomy, so the latter is rarely done. Amputationis a procedure of last resort, indicated for uncontrolled infection, unrelenting rest pain, and progressive gangrene. Amputation should be as distal as possible, preserving the knee for optimal use with a prosthesis. External pneumatic compression of the lower limb to increase distal blood flow is an option for limb salvage in patients who have severe PAD and are not candidates for surgery. Theoretically, it controls edema and improves arterial flow, venous return, and tissue oxygenation, but data supporting its use are lacking. Pneumatic cuffs or stockings are placed on the lower leg and inflated rhythmically during diastole, systole, or part of both periods for 1 to 2 hours several times a week. Bone marrow stem cells can differentiate into small blood vessels. Clinical trials are investigating autologous iliac crest bone marrow stem cell transplantation into legs of patients with critical limb ischemia. Although this therapy may not be appropriate for every patient, it may prove to be an alternative for some who would otherwise need major amputation; results of initial smaller trials have been encouraging but some blinded, placebo-controlled trials have failed to show benefit ( Treatment references ). Gene therapy is also being studied ( Treatment references ). Gene transfer of DNA encoding VEGF may promote collateral blood vessel growth. 1.Anand S, Bosch J, Eikelboom JW, et al, on behalf of the COMPASS Investigators:Rivaroxabanwith or withoutaspirinin patients with stable peripheral or carotid artery disease: an international, randomized, double-blind, placebo controlled trial.Lancet391(10117):218–229, 2018. doi: 10.1016/S0140-6736(17)32409-1 2.Bonaca MP, Bauersachs RM, Anand SS, et al:Rivaroxabanin peripheral artery disease after revascularization.N Engl J Med382:1994–2004, 2020. doi: 10.1056/NEJMoa2000052 3.Gerhard-Herman MD, Gornik HL, Barrett C, et al: 2016 AHA/ACC Guideline on the management of patients with lower extremity peripheral artery disease.Circulation155:e686–e725, 2017. 4.Hiatt WR, Bonaca MP, Patel MR, et al.RivaroxabanandAspirinin Peripheral Artery Disease Lower Extremity Revascularization.Circulation142 (23):2219-2230, 2020. doi/10.1161/CIRCULATIONAHA.120.050465 5.Khan SZ, O'Brien-Irr MS, Rivero M, et al. Improved survival with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic limb-threatening ischemia.J Vasc Surg2020;72(6):2130-2138. doi:10.1016/j.jvs.2020.02.041 6.Ipema J, Huizing E, Schreve MA, de Vries JPM, Ünlü Ç. Editor's Choice - Drug Coated Balloon Angioplasty vs. Standard Percutaneous Transluminal Angioplasty in Below the Knee Peripheral Arterial Disease: A Systematic Review and Meta-Analysis. Eur J Vasc Endovasc Surg. 2020;59(2):265-275. doi:10.1016/j.ejvs.2019.10.002 7.Rigato M, Monami M, Fadini GP: Autologous cell therapy for peripheral arterial disease: Systematic review and meta-analysis of randomized, nonrandomized, and noncontrolled studies.Circ Res120(8):1326–1340, 2017. doi: 10.1161/CIRCRESAHA.116.309045 8.Teraa M, Sprengers RW, Schutgens RE, et al: Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: The randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial.Circulation131(10):851–860, 2015. doi: 10.1161/CIRCULATIONAHA.114.012913 9.Forster R, Liew A, Bhattacharya V, Shaw J, Stansby G: Gene therapy for peripheral arterial disease.Cochrane Database Syst Rev2018;10(10):CD012058. Published 2018 Oct 31. doi:10.1002/14651858.CD012058.pub2 10.Shimamura M, Nakagami H, Sanada F, Morishita R. Progress of Gene Therapy in Cardiovascular Disease.Hypertension2020;76(4):1038-1044. doi:10.1161/HYPERTENSIONAHA.120.14478 