Saman L Parvar1, Robert Fitridge2, Joseph Dawson3, Stephen J Nicholls4. 1. Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia. Electronic address: saman.parvar@adelaide.edu.au. 2. Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia; Department of Vascular Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 3. Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia; Department of Vascular Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 4. Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Abstract
OBJECTIVE: Peripheral arterial disease (PAD) is a global health issue associated with impaired functional capacity and elevated risk of major adverse cardiovascular events (MACEs). With changing risk factor profiles and an aging population, the burden of disease is expected to increase. This review considers evidence for the noninvasive management of PAD and makes clinical recommendations accordingly. METHODS: A comprehensive literature review was performed to examine the evidence for smoking cessation, exercise therapy, antiplatelet therapy, anticoagulant therapy, antihypertensive therapy, lipid-lowering therapy, and glycemic control in diabetes for patients with PAD. RESULTS: Nicotine replacement, bupropion, and varenicline are safe and more effective than placebo in achieving smoking abstinence. Wherever it is practical and available, supervised exercise therapy is ideal treatment for intermittent claudication. Alternatively, step-monitored exercise can increase walking performance and the participant's compliance with less staff supervision. Clopidogrel is preferable to aspirin alone for all patients. However, small studies support the use of dual antiplatelet therapy after revascularization to improve limb outcomes. More recently, the addition of low-dose rivaroxaban to aspirin alone was proven to be more effective in reducing MACEs without a significant increase in major bleeding. However, the exact role of direct oral anticoagulant therapy in the management of PAD is still being understood. Evidence is emerging for more intensive blood pressure and lipid-lowering therapy than traditional targets. Whereas research in PAD is limited, there is clinical scope for an individualized approach to these risk factors. The management of diabetes remains challenging as glycemic control has not been demonstrated to improve macrovascular outcomes. Any potential impact of glycemic control on microvascular disease needs to be weighed against the risks of hypoglycemia. Sodium-glucose cotransporter 2 inhibitors appear to reduce MACEs, although caution is advised, given the increased incidence of lower limb amputation in clinical trials of canagliflozin. CONCLUSIONS: Medical and lifestyle management of PAD should aim to improve functional outcomes and to reduce MACEs. Smoking cessation counseling or pharmacotherapy is recommended, although new strategies are needed. Whereas supervised exercise therapy is ideal, there can be barriers to clinical implementation. Other initiatives are being used as an alternative to walking-based supervised exercise therapy. More studies are required to investigate the role of intensive glycemic, blood pressure, and dyslipidemia control in patients with PAD. Overall, a multifactorial approach is recommended to alter the natural history of this condition.
OBJECTIVE:Peripheral arterial disease (PAD) is a global health issue associated with impaired functional capacity and elevated risk of major adverse cardiovascular events (MACEs). With changing risk factor profiles and an aging population, the burden of disease is expected to increase. This review considers evidence for the noninvasive management of PAD and makes clinical recommendations accordingly. METHODS: A comprehensive literature review was performed to examine the evidence for smoking cessation, exercise therapy, antiplatelet therapy, anticoagulant therapy, antihypertensive therapy, lipid-lowering therapy, and glycemic control in diabetes for patients with PAD. RESULTS:Nicotine replacement, bupropion, and varenicline are safe and more effective than placebo in achieving smoking abstinence. Wherever it is practical and available, supervised exercise therapy is ideal treatment for intermittent claudication. Alternatively, step-monitored exercise can increase walking performance and the participant's compliance with less staff supervision. Clopidogrel is preferable to aspirin alone for all patients. However, small studies support the use of dual antiplatelet therapy after revascularization to improve limb outcomes. More recently, the addition of low-dose rivaroxaban to aspirin alone was proven to be more effective in reducing MACEs without a significant increase in major bleeding. However, the exact role of direct oral anticoagulant therapy in the management of PAD is still being understood. Evidence is emerging for more intensive blood pressure and lipid-lowering therapy than traditional targets. Whereas research in PAD is limited, there is clinical scope for an individualized approach to these risk factors. The management of diabetes remains challenging as glycemic control has not been demonstrated to improve macrovascular outcomes. Any potential impact of glycemic control on microvascular disease needs to be weighed against the risks of hypoglycemia. Sodium-glucose cotransporter 2 inhibitors appear to reduce MACEs, although caution is advised, given the increased incidence of lower limb amputation in clinical trials of canagliflozin. CONCLUSIONS: Medical and lifestyle management of PAD should aim to improve functional outcomes and to reduce MACEs. Smoking cessation counseling or pharmacotherapy is recommended, although new strategies are needed. Whereas supervised exercise therapy is ideal, there can be barriers to clinical implementation. Other initiatives are being used as an alternative to walking-based supervised exercise therapy. More studies are required to investigate the role of intensive glycemic, blood pressure, and dyslipidemia control in patients with PAD. Overall, a multifactorial approach is recommended to alter the natural history of this condition.