Peripheral Artery Disease: Symptoms, Causes, Diagnosis, and Treatment Options

Peripheral artery disease (PAD) is a common condition in which narrowed arteries, usually caused by atherosclerosis, reduce blood flow to the limbs, most often the legs. It affects an estimated 200 million people worldwide and ranges from asymptomatic disease to leg pain during walking (claudication) to its most severe form, critical limb ischemia (CLI), where blood flow is so reduced that rest pain, non-healing ulcers, or gangrene can occur, carrying a real risk of amputation. Standard treatment includes lifestyle changes, medication, and revascularization procedures. For a narrow group of “no-option” CLI patients who’ve exhausted these options, a stem cell-based therapy called Stempeucel has actually received regulatory approval in India — though internationally, cell therapy for PAD is still generally classified as investigational, with mixed results in rigorous trials.

PAD occurs when fatty plaque buildup (atherosclerosis) narrows the arteries supplying blood to the limbs. It’s generally categorized into stages:

• Asymptomatic PAD — no symptoms, though blood flow may already be measurably reduced
• Chronic symptomatic PAD — intermittent claudication, meaning pain, cramping, or fatigue in the legs during walking or exercise that eases with rest
• Critical limb ischemia (CLI, also called chronic limb-threatening ischemia) — the most severe stage, involving persistent rest pain, non-healing ulcers, or gangrene due to critically reduced blood flow

• Leg pain, cramping, or heaviness during walking or exercise (claudication), typically relieved by rest
• Coldness in the lower leg or foot, especially compared to the other side
• Numbness or weakness in the legs
• Hair loss on the legs, or shiny, pale, or dry skin
• Wounds or ulcers on the legs or feet that heal slowly or not at all
• A weak or absent pulse in the legs or feet
• In advanced disease, pain even at rest, and discoloration of the toes or feet

Many people with PAD have no noticeable symptoms in daily life and are diagnosed through screening, particularly if they have risk factors.

Atherosclerosis is the underlying cause in the large majority of cases. Key risk factors include:

• Smoking — one of the strongest risk factors for PAD
• Diabetes
• High blood pressure and high cholesterol
• Older age
• Family history of cardiovascular disease
• Obesity and sedentary lifestyle

PAD frequently coexists with cardiovascular and cerebrovascular disease, since atherosclerosis is a systemic process — having PAD meaningfully raises the risk of heart attack and stroke as well, not just limb-related complications.

• Ankle-brachial index (ABI) — comparing blood pressure in the ankle to the arm is the primary, non-invasive first-line test
• Doppler ultrasound — assesses blood flow and identifies blockages
• CT angiography or MR angiography — provides detailed imaging of the arteries when more precise mapping is needed, particularly before intervention
• Digital subtraction angiography (DSA) — an invasive imaging technique sometimes used during planned intervention

• Risk factor modification — smoking cessation, blood pressure and cholesterol management, and diabetes control are foundational
• Structured exercise therapy — supervised walking programs have strong evidence for improving walking distance and symptoms in claudication
• Medications — antiplatelet agents, cholesterol-lowering medications, and in some cases medications specifically aimed at improving walking distance
• Revascularization procedures — angioplasty (with or without stenting) or bypass surgery to restore blood flow, typically reserved for more severe or treatment-resistant cases

This is an area where it’s important to separate two different pictures: the international evidence base, and a specific, real regulatory development in India.

The international evidence picture is cautious. Cell-based therapy for PAD and critical limb ischemia has been studied primarily in phase 2 trials, using various cell types (bone marrow-derived cells, mobilized peripheral blood cells, mesenchymal stromal cells) and administration methods. A meta-analysis of the trials with the lowest risk of bias found no significant benefit of stem cell therapy on overall survival, amputation-free survival, or amputation rates. Reflecting this, major US health insurers currently classify stem cell therapy for PAD, including critical limb ischemia, as investigational and not medically necessary.

India has a specific, real exception worth knowing about. Stempeucel (marketed as REGENACIP), a pooled allogeneic bone marrow-derived mesenchymal stromal cell product, received manufacturing and marketing approval from India’s Central Drugs Standard Control Organisation (CDSCO) in 2020 — the first such approval globally for this indication. It’s approved specifically for “no-option” patients with critical limb ischemia due to Buerger’s disease or atherosclerotic PAD (Rutherford grade III-5 or III-6) who are not eligible for, or have failed, standard revascularization, and who have rest pain and/or ulcers. A Phase III study supporting this approval was published in 2023, and the product has now treated over 600 patients in India, with a post-marketing surveillance study currently underway.

How to reconcile these two pictures: India’s regulatory approval reflects a specific, narrow patient population and a specific product with its own trial data — it does not mean stem cell therapy broadly works for all PAD or CLI patients, and it exists alongside continued caution from international bodies reviewing the wider evidence base. Even India’s own Indian Council of Medical Research (ICMR) has noted that, despite this specific approval, stem cell therapy should generally not be offered as routine standard therapy for CLI outside of this defined, evidence-supported indication.

• If you have PAD, the proven first steps are risk factor management, supervised exercise, medication, and — when needed — revascularization
• Cell therapy is not a substitute for these standard approaches, and is relevant only for a specific, severe “no-option” subset of CLI patients who have exhausted conventional treatment
• Any discussion of cell therapy should include an honest look at both the specific India-approved indication and the broader international evidence, not one without the other

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Have questions about your specific case? Book a free case review and our medical team can give you an honest picture of your options, including whether the specific India-approved indication for critical limb ischemia applies to your situation.