Lower-Extremity PAD: Epidemiology, Diagnosis, Claudication, Exercise, and Medical Therapy

35.1Lower-extremity PAD care: the questions a vascular clinician actually faces

Lower-extremity peripheral artery disease is not simply a question of whether an artery is narrowed. The clinical task is to decide whether the patient has PAD, whether the symptoms are attributable to PAD, whether the limb is stable, and whether the dominant therapeutic need is risk reduction, walking restoration, or procedural planning. For the vascular trainee, the first discipline is to keep these questions separate. A patient may have an abnormal ankle-brachial index and no exertional symptoms; another may have classic claudication and a revascularizable iliac lesion; a third may have diabetes, chronic kidney disease, and noncompressible tibial arteries that make a normal-looking ankle pressure misleading. The chapter therefore begins with diagnosis and medical therapy because every downstream decision rests on those foundations ACC/AHA 2024 · Measurement interpretation ankle-brachial 2012.

The second discipline is to recognize that PAD is a systemic atherosclerotic disease expressed in the leg. The walking complaint matters, but so does the patient’s future myocardial infarction, ischemic stroke, acute limb event, and need for durable longitudinal care. Trials of antiplatelet therapy, dual-pathway antithrombotic therapy, statin use, and exercise have all shaped contemporary management because they address different hazards: thrombosis, cardiovascular events, limb ischemia, and functional decline Exercise intermittent claudication. 2014 · Rivaroxaban Peripheral Artery 2020 · Rivaroxaban Aspirin Stable 2017 · CAPRIE 1996.

The practical caveat is that “best medical therapy” is not a slogan. In real practice, many patients with PAD are not prescribed the medicines they should receive, and many who are prescribed therapy do not take it consistently. A systematic review and meta-analysis including 125 PAD studies and 14,681,801 participants estimated underprescription rates of 28% for antiplatelet therapy, 34% for statins, and 43% for antihypertensives; nonadherence clustered near one quarter of prescribed patients Clinician underprescription patient 2025. For antithrombotic therapy specifically, a systematic review of 10 PAD studies including 32,628 patients found poor adherence ranging from 2% to 45%, summarized at roughly one third, especially in longer follow-up and pharmacy- or registry-measured cohorts Medication adherence patients 2025.

Diabetes management illustrates the need for vascular judgment rather than reflexive protocol-following. In CANVAS, canagliflozin reduced the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in 10,142 high-risk patients with type 2 diabetes, but amputation events were higher with canagliflozin than with placebo, at 6.3 versus 3.4 events per 1000 patient-years, hazard ratio 1.97 Canagliflozin Cardiovascular Renal 2017. That signal does not turn PAD care into avoidance of cardiovascular risk reduction; it does mean that a vascular clinician should be alert to foot risk, limb history, and amputation vigilance when diabetes drugs are selected in patients with established or suspected PAD.

A calm PAD consultation therefore has a reproducible structure. Confirm the syndrome, measure physiologic disease when indicated, stratify cardiovascular and limb risk, prescribe durable secondary prevention, and decide whether the patient’s claudication warrants structured exercise alone, revascularization plus exercise, or continued conservative care. The resident should learn to state the decision explicitly: “This patient has symptomatic PAD by history and ABI; the current priority is walking improvement and cardiovascular risk reduction, not limb salvage.” That sentence prevents the common error of treating every abnormal arterial test as a procedural indication ESVS 2024 · ACC/AHA 2024 · Aboyans ESC lower-limb PAD 2017.

35.2Who has lower-limb PAD, and why the prevalence keeps rising

Lower-extremity PAD is common enough that vascular clinicians must think in populations as well as individual consultations. The 2024 AHA statistical update estimates that lower-extremity PAD affects more than 8 million adults in the United States and more than 230 million people worldwide AHA Statistics 2024. The burden rises sharply with age, especially among older adults, and is disproportionately concentrated among Black adults and among patients with diabetes or chronic kidney disease. This epidemiology matters at the bedside because the patient with vague exertional leg symptoms and multiple risk factors may have PAD even before the story becomes textbook claudication ACC/AHA 2024.

The prevalence continues to rise because PAD tracks aging, diabetes, chronic kidney disease, smoking exposure, and atherosclerosis in other vascular beds. The vascular surgeon sees this most clearly in mixed-risk patients: an older former smoker with diabetes and coronary disease; a patient with chronic kidney disease and noncompressible ankle arteries; or a patient whose walking limitation has been dismissed as aging until an ABI is finally obtained. The guideline framing is practical: ABI testing is recommended for adults with symptoms suggestive of PAD and for adults at increased risk, including older adults, smokers, patients with diabetes, and patients with atherosclerotic disease elsewhere ACC/AHA 2024.

At the same time, PAD prevalence does not justify indiscriminate population testing. The 2024 ACC/AHA PAD guideline does not recommend universal screening of asymptomatic adults ACC/AHA 2024. The 2017 ESC PAD guideline similarly discourages routine population screening of asymptomatic adults Aboyans ESC lower-limb PAD 2017. This distinction is important for trainees: targeted testing is not “screening everyone.” It is using symptoms and risk profile to decide who deserves a physiologic vascular assessment.

The other epidemiologic truth is therapeutic underdelivery. PAD is tracked as a major heart and circulatory disease, including outcomes, procedures, quality of care, and economic burden, yet medical treatment frequently falls short AHA Statistics 2024. The implementation gap is large: underprescription of antiplatelet therapy, statins, and antihypertensives remains common across PAD studies, and adherence is imperfect even when prescriptions are written Medication adherence patients 2025 · Clinician underprescription patient 2025. For a vascular service, this means that every new PAD diagnosis should trigger a medication reconciliation, not merely an arterial imaging request.

A useful resident habit is to identify the patient’s PAD phenotype in the first note. Write whether the patient is asymptomatic with abnormal testing, has intermittent claudication, has recently undergone lower-extremity revascularization, or is being evaluated for more advanced limb threat addressed in adjacent chapters. Then document the risk factors that justified testing: age, smoking, diabetes, kidney disease, or atherosclerotic disease in another bed ACC/AHA 2024 · AHA Statistics 2024. This makes the consultation defensible and helps the next clinician understand why PAD is being treated as a longitudinal vascular disease rather than a single-visit leg complaint.

At the bedside, document the indication, timing, and escalation trigger before choosing surveillance, imaging, intervention, or deferral.

35.3Ankle-brachial index, toe-brachial index, and the rest of the diagnostic pathway

The ankle-brachial index remains the first physiologic test that makes PAD visible in routine practice. A resting ABI of 0.90 or lower defines lower-extremity PAD, with sensitivity above 80% and specificity above 95% compared with angiography Measurement interpretation ankle-brachial 2012. The test should be ordered when symptoms suggest PAD or when the patient is at increased risk by age, smoking, diabetes, atherosclerotic disease elsewhere, or related clinical context ACC/AHA 2024. For the trainee, the key is not merely obtaining an ABI; it is matching the result to the clinical story and documenting what the result means.

ABI interpretation should be explicit. An ABI of 0.90 or lower is abnormal and supports the diagnosis of PAD ACC/AHA 2024 · Measurement interpretation ankle-brachial 2012. An ABI greater than 1.40 indicates noncompressible arteries, often reflecting medial calcification in patients with diabetes or chronic kidney disease, and should not be treated as reassuring. In that setting, toe-brachial index is the usual next physiologic reference point; a TBI of 0.70 or lower is abnormal. Pulse-volume recording or duplex can also help when ankle pressures are unreliable.

The diagnostic pathway should prevent two common errors. The first is overcalling PAD in a patient whose exertional leg pain has no physiologic support. The second is undercalling PAD in a patient with diabetes or chronic kidney disease whose ankle arteries cannot be compressed and whose ABI is falsely elevated. The ABI statement specifically warns that diagnostic accuracy degrades with noncompressible vessels, which is why the toe-brachial index and waveform-based tests are not optional refinements in these patients; they are part of making the diagnosis responsibly Measurement interpretation ankle-brachial 2012.

The rest of the pathway depends on the clinical question. If the question is diagnosis, ABI and TBI thresholds often settle the issue. If the question is whether claudication therapy is working, repeat physiologic assessment may be paired with functional history. If the question is revascularization planning, anatomic imaging belongs later, after the clinician has established that PAD is present and that symptoms justify procedural consideration. Guidelines converge on ABI-based diagnosis and on reserving revascularization for selected symptomatic patients rather than for every abnormal test ESVS 2024 · ACC/AHA 2024 · Aboyans ESC lower-limb PAD 2017.

Exercise therapy is not a soft recommendation; it is one of the central treatments for intermittent claudication. A Cochrane review of exercise for intermittent claudication included 30 randomized trials and 1,816 participants and found that exercise programs improved treadmill walking time and distance compared with usual care or medical therapy across follow-up intervals ranging from weeks to two years Exercise intermittent claudication. 2014. When supervised exercise was compared with non-supervised exercise, walking advice, or home-based approaches, 14 trials including 1,002 participants showed better maximal treadmill walking distance at 3 and 6 months, translating to roughly 180 meters more walking distance in favor of supervised programs Supervised exercise therapy 2013.

A vascular note should document the indication, the numeric result, and the interpretive category. A concise entry is sufficient: “ABI obtained for exertional calf symptoms in a diabetic former smoker; right ABI 0.72, left ABI 1.48; right result supports PAD, left result is noncompressible and requires TBI/waveform correlation.” This kind of documentation matters because it prevents later clinicians from treating a high ABI as normal and because it records why further testing was necessary ACC/AHA 2024 · Measurement interpretation ankle-brachial 2012.

The CLEVER trial is particularly useful for the trainee because it challenges the instinct to stent every proximal claudication lesion first. In 111 patients with aortoiliac intermittent claudication suitable for supervised exercise, primary stenting, or optimal medical care, peak walking time at 6 months increased by about 5.8 minutes with supervised exercise, 3.7 minutes with stenting, and 1.2 minutes with optimal medical care CLEVER 2012. Both exercise and stenting improved symptoms, but supervised exercise was superior to stenting for change in peak walking time. The practical lesson is not that iliac stenting is ineffective; it is that supervised exercise should be treated as active therapy, even in proximal disease.

ERASE adds a complementary message. In 212 patients with lifestyle-limiting intermittent claudication suitable for both supervised exercise and endovascular intervention, endovascular revascularization plus supervised exercise produced greater maximum treadmill walking distance at one-year follow-up than supervised exercise alone, approximately 1501 meters versus 1240 meters, with a mean difference of about 282 meters; quality-of-life measures also favored combined therapy Erase JAMA 2015. Thus, the mature claudication plan is staged and individualized: begin with medical therapy and supervised exercise when appropriate, but consider combined therapy when symptoms remain lifestyle-limiting and the anatomy is suitable ESVS 2024.

Antiplatelet therapy is part of the symptomatic PAD backbone. CAPRIE randomized 19,185 patients with recent ischemic stroke, recent myocardial infarction, or symptomatic PAD to clopidogrel 75 mg daily or aspirin 325 mg daily CAPRIE 1996. The annual rate of ischemic stroke, myocardial infarction, or vascular death was 5.32% with clopidogrel versus 5.83% with aspirin, with a relative risk reduction of approximately 8.7% favoring clopidogrel; the largest absolute benefit was observed in the symptomatic-PAD subgroup. For the resident, this supports clopidogrel monotherapy as a strong option in symptomatic PAD when single antiplatelet therapy is selected.

Dual-pathway inhibition is a separate decision from antiplatelet monotherapy. In COMPASS, 27,395 patients with stable coronary or peripheral atherosclerotic disease were randomized to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin alone Rivaroxaban Aspirin Stable 2017. The composite of cardiovascular death, stroke, or myocardial infarction decreased from 5.4% to 4.1%, hazard ratio 0.76, while major bleeding increased from 1.9% to 3.1%. In the PAD subgroup, reduction in major adverse limb events was clinically meaningful. The bedside judgment is to identify patients whose ischemic and limb risk justify treatment intensification and whose bleeding risk is acceptable.

After lower-extremity revascularization, VOYAGER PAD gives the key trial reference point. In 6,564 patients undergoing lower-extremity revascularization, rivaroxaban 2.5 mg twice daily plus aspirin reduced the 3-year composite of acute limb ischemia, major amputation, myocardial infarction, ischemic stroke, or cardiovascular death from 19.9% to 17.3%, hazard ratio 0.85, compared with aspirin alone Rivaroxaban Peripheral Artery 2020. Major bleeding was numerically increased, with an ISTH hazard ratio of approximately 1.4. This is the practical post-revascularization discussion: the regimen reduces ischemic and limb events, but the patient must be able to accept the bleeding tradeoff and adhere to therapy Medication adherence patients 2025.

Lipid and diabetes therapies should be discussed as vascular prevention rather than as separate specialty chores. In a nationwide cohort of 24,665 women hospitalized with coronary, cerebrovascular, or peripheral artery disease, statin therapy was associated with lower all-cause mortality in the PAD subgroup, hazard ratio 0.72 with 95% confidence interval 0.64–0.81, although cardiovascular hospitalization reduction was not significant for PAD Statins secondary prevention 2025. In SUSTAIN-6, semaglutide reduced the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in high-cardiovascular-risk patients with type 2 diabetes, 6.6% versus 8.9%, hazard ratio 0.74, while retinopathy complications were higher Semaglutide Cardiovascular Outcomes 2016. In CANVAS, canagliflozin reduced major cardiovascular events but increased amputation events, which is why PAD clinicians should preserve foot vigilance when these agents are used in high-risk diabetic patients Canagliflozin Cardiovascular Renal 2017.

The future of antithrombotic therapy may include more selective coagulation targets, but that should not be converted into current PAD treatment advice. Mechanistic literature on the intrinsic/contact pathway supports a distinction between thrombosis and protective hemostasis, with inhibition of FXI, FXII, and prekallikrein reducing thrombosis in preclinical models while having limited effect on normal hemostatic pathways Intrinsic Pathway Coagulation 2019. For now, this belongs in the trainee’s conceptual framework, not in a PAD prescription template.

35.5Major lower-extremity PAD guidelines — where they line up and where they differ

The major contemporary guidelines line up on the central principles of PAD care. ABI is the diagnostic entry point, with 0.90 or lower defining PAD, and noncompressible vessels requiring alternative physiologic testing ACC/AHA 2024 · Aboyans ESC lower-limb PAD 2017 · Measurement interpretation ankle-brachial 2012. Symptomatic patients and patients at increased risk deserve targeted assessment, while routine population screening of asymptomatic adults is discouraged. All three frameworks treat PAD as both a limb disease and a systemic cardiovascular-risk condition ESVS 2024.

For intermittent claudication, the European vascular, European cardiology, and American approaches also converge more than they differ. Supervised exercise is first-line therapy for intermittent claudication ESVS 2024 · Aboyans ESC lower-limb PAD 2017. Revascularization is reserved for patients with persistent lifestyle-limiting symptoms after exercise-based therapy, or for selected short proximal lesions where endovascular durability is favorable. This is consistent with trial evidence showing that supervised exercise improves walking performance and that combined endovascular therapy plus supervised exercise can improve walking distance in selected lifestyle-limited patients Erase JAMA 2015 · CLEVER 2012.

Best medical therapy is not optional in any guideline framework. The ESVS 2024 PAD guidance requires antiplatelet therapy, statin therapy, and blood-pressure control for PAD patients regardless of symptom status ESVS 2024. The Aboyans ESC lower-limb PAD 2017 guideline recommends antiplatelet plus statin therapy for all symptomatic PAD patients Aboyans ESC lower-limb PAD 2017. The American framework similarly places diagnostic testing, risk-factor treatment, and antithrombotic decisions within a longitudinal PAD-care model ACC/AHA 2024. The difference at the bedside is rarely whether prevention is needed; it is whether the clinician actually prescribes it, reconciles it, and follows adherence Medication adherence patients 2025 · Clinician underprescription patient 2025.

Where guidelines differ in emphasis, the vascular surgeon should translate them into a patient-specific decision rather than a territorial debate. A patient with mild claudication, newly diagnosed PAD, and no prior exercise program should not be rushed to revascularization simply because an anatomic lesion is present ESVS 2024 · Aboyans ESC lower-limb PAD 2017. A patient with severe lifestyle-limiting claudication despite supervised exercise and suitable proximal anatomy may reasonably be considered for endovascular therapy, particularly when the goal is functional restoration rather than limb salvage Erase JAMA 2015. A patient after lower-extremity revascularization may merit intensified antithrombotic therapy if ischemic benefit outweighs bleeding risk Rivaroxaban Peripheral Artery 2020.

The main failure mode is oversimplification. “Exercise first” should not become neglect of a disabled patient with persistent symptoms. “Revascularization works” should not become procedural treatment of every abnormal test. “Antithrombotic intensification reduces events” should not become automatic therapy in a patient at unacceptable bleeding risk or a patient unlikely to adhere. Guideline-concordant PAD care requires the surgeon to integrate symptoms, physiology, anatomy, cardiovascular risk, bleeding risk, and patient goals into a plan that can actually be carried out ESVS 2024 · ACC/AHA 2024 · Rivaroxaban Peripheral Artery 2020 · Rivaroxaban Aspirin Stable 2017.

At the bedside, document the indication, timing, and escalation trigger before choosing surveillance, imaging, intervention, or deferral.