What are the causes of intermittent claudication in Peripheral Arterial Disease (PAD)?

From the Guidelines

Peripheral arterial disease (PAD) causing leg pain should be promptly evaluated by a healthcare provider, with a focus on meticulous clinical history assessment and thorough vascular examination, as outlined in the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline 1. When evaluating leg pain, it is essential to consider alternative diagnoses, such as hip arthritis, foot/ankle arthritis, nerve root compression, spinal stenosis, symptomatic popliteal (Baker’s) cyst, venous claudication, and chronic compartment syndrome, as these conditions can present with similar symptoms to PAD 1. Key characteristics of these alternative diagnoses include:

• Hip arthritis: aching discomfort in the lateral hip and thigh, worsened by exercise and improved by rest and not bearing weight 1
• Foot/ankle arthritis: aching pain in the ankle, foot, and arch, worsened by exercise and improved by rest and not bearing weight 1
• Nerve root compression: sharp lancinating pain radiating down the leg, induced by sitting, standing, or walking, and improved by changing position 1
• Spinal stenosis: pain and weakness in the bilateral buttocks and posterior leg, worsened by standing and extending the spine, and improved by lumbar spine flexion 1
• Symptomatic popliteal (Baker’s) cyst: swelling and tenderness behind the knee and down the calf, worsened by exercise and present at rest 1
• Venous claudication: tight, bursting pain in the entire leg, worsened by walking and improved by leg elevation 1
• Chronic compartment syndrome: tight, bursting pain in the calf muscles, worsened by strenuous exercise and improved by rest 1 A thorough vascular examination should include palpation of lower extremity pulses, evaluation for abdominal and femoral bruits, and assessment for signs of PAD, such as elevation pallor/dependent rubor, asymmetric hair growth, and calf muscle atrophy 1. Treatment of PAD typically includes lifestyle modifications, such as stopping smoking immediately, beginning a structured walking program, and medications, including antiplatelet drugs, statins, ACE inhibitors, and cilostazol, to prevent blood clots, lower cholesterol, and reduce cardiovascular risk 1. Regular medical follow-up is essential to monitor disease progression and treatment effectiveness.

From the Research

Peripheral Arterial Disease (PAD) and Leg Pain

• PAD is a prevalent but underdiagnosed manifestation of atherosclerosis that has a worse prognosis than coronary artery disease 2
• Patients with PAD are at heightened risk of both systemic cardiovascular adverse events and limb-related morbidity 2
• Leg pain is a central hallmark of PAD, which may present as intermittent claudication, atypical leg pain, ischemic rest pain, neuropathic pain, or phantom limb pain 3

Risk Factors and Treatment

• Smoking should be stopped, and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism should be treated in patients with PAD 4, 5
• Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia 4, 5
• Antiplatelet drugs, such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors, and statins, should be given to all patients with PAD without contraindications to these drugs 4, 5
• Beta-blockers should be given if coronary artery disease is present 4, 5
• Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops 4, 5

Antithrombotic Treatment

• In symptomatic PAD, single antiplatelet therapy (SAPT) with aspirin or clopidogrel is indicated 6
• Clopidogrel may be preferred over aspirin 6
• Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin does not provide benefit over SAPT with aspirin alone and is associated with increased risk of major bleeding 6
• Rivaroxaban (2.5 mg b.i.d.) plus aspirin (100 mg daily) is the first antithrombotic association that proved significant benefit for PAD patients, in terms of strong endpoints - total mortality and cardiovascular mortality 6

Pain Management

• Pain in PAD results in severe disability and can copresent with distress, sickness behaviors, and concomitant depression, anxiety, and addiction secondary to opioid use 3
• Multimodal pain management strategies that emphasize a biopsychosocial model have generated a solid evidence base for the use of cognitive behavioral approaches to manage pain 3
• Multimodal pain management in PAD is not the norm, but theoretical pathways and road maps for further research, assessment, and clinical implementation are presented in the literature 3