Peripheral Arterial Disease and Chronic Limb-Threatening Ischaemia — Claudication Exercise, WIfI-PLAN-GLASS Staging, BEST-CLI versus BASIL-2 Revascularisation, and Vascular-Dose Rivaroxaban

A 66-year-old smoker with 200-metre calf claudication, a 74-year-old woman with forefoot rest pain and a heel ulcer present for a month, and a 70-year-old man with a diabetic plantar ulcer and absent foot pulses. One needs an exercise prescription with honest metre-gains, one needs urgent vascular referral with WIfI staging and a PLAN-based revascularisation choice, and one needs arterial assessment because half of diabetic foot ulcers carry PAD. The examiner will watch you define PAD at ABI 0.90 or below, split claudication from CLTI by the 2-week tissue-loss line, hold exercise as first line by Cochrane and CLEVER, choose bypass versus endo by conduit and anatomy per BEST-CLI and BASIL-2, and add rivaroxaban after revascularisation by VOYAGER — with every number taken from the papers named beside it.^{[1][4][16][8][9]}

Overview & Definition — the 0.90 line, the 2-week line, and the continuum

Peripheral artery disease enters the epidemiologic record at an ankle brachial index of 0.90 or below — the community-study definition behind every global number in this topic.^[1][2] Chronic limb-threatening ischaemia is the clinical syndrome of PAD plus rest pain, gangrene, or a lower-limb ulceration beyond 2 weeks, excluding venous, traumatic, embolic and nonatherosclerotic causes.^[4] The guideline deliberately prefers CLTI over critical limb ischaemia because the older term implies perfusion thresholds rather than a continuum.^[4] The strategic arc fits one sentence: claudication is managed for function with exercise first, CLTI is staged by limb, patient and anatomy then revascularised by conduit logic, and every revascularised leg gets best medical therapy with vascular-dose rivaroxaban where bleeding risk allows.^[16][4][9]

Classification — three stagings for three different questions

• WIfI stages the limb: wound, ischaemia and foot infection jointly set amputation risk and management — perfusion is only one determinant, and wound extent plus infection severity also greatly impact the threat.^[5]
• GLASS stages the arteries: define the preferred target artery path, estimate limb-based patency, and read off three complexity stages for intervention.^[4]
• PLAN stages the decision: patient risk, limb severity and anatomic complexity are three independent axes, and the vein-bypass preference rule runs on them — vein bypass may suit average-risk advanced-threat high-complexity disease, while less complex anatomy, intermediate threat or high patient risk may favour endovascular intervention.^[4]
• Fontaine and Rutherford are the older two-group habit: they split ischaemic rest pain from tissue loss only, which fails in diabetic limbs where wound and infection dominate — name their limit, never their stage numbers.^[5]
• The 2024 multisociety PAD guideline frames the presentations: asymptomatic, chronic symptomatic, CLTI and acute limb ischaemia subsets — this topic owns the middle two.^[3]

Each staging answers a different viva question — limb threat, arterial complexity, then the revascularisation choice.^[4][5]

Epidemiology & Risk Factors — the denominators that frame every decision

In 2010, 202 million people lived with PAD and 69.7% of them were in low- and middle-income countries, including 54.8 million in southeast Asia and 45.9 million in the western Pacific.^[1] By 2015 the count reached 236.62 million people aged 25 and older at a global prevalence of 5.56%, with 72.91% in LMICs and the Western Pacific holding the most cases at 74.08 million against 14.67 million in the Eastern Mediterranean.^[2] The clinic face of those numbers: PAD affects between 4% and 12% of people aged 55 to 70 and 20% of those over 70, carrying a three- to six-fold increase in cardiovascular mortality.^[17]

Risk concentrates where the surgeon already counsels: smoking leads in both high-income and low/middle-income settings with meta-odds of 2.72 and 1.42 for current smoking, followed by diabetes, hypertension and hypercholesterolaemia in that order.^[1] The revascularisation trials randomise at scale: BASIL-1 452 patients, BASIL-2 345, BEST-CLI 1830, VOYAGER 6564, EUCLID 13,885, CAPRIE 19,185, CLEVER 111, ERASE 212, and the Almasri synthesis 44 studies with 8602 patients.^{[6][7][8][9][11][12][14][15][20]}

Clinical Presentation — claudicant, rest pain, tissue loss, diabetic foot

The claudicant declares through exertion: stable leg pain on walking in the Cochrane, CLEVER and ERASE populations, measured on treadmills in pain-free and maximum distances.^[16][14][15] The CLTI leg declares through rest or loss: ischaemic rest pain, gangrene, or an ulcer beyond 2 weeks — and every suspected CLTI leg goes urgently to a vascular specialist.^[4] The diabetic foot declares through overlap: approximately half of diabetic foot ulcers carry PAD, which significantly raises limb and cardiovascular risk — so the ulcer is an arterial case until proven otherwise.^[19] The post-MALE leg declares through jeopardy: after severe limb ischaemia requiring intervention or major amputation, the 1-year toll is 61.5% rehospitalised, 20.5% amputated, 8.3% dead and 3.7% with major cardiovascular events — prevention outranks salvage.^[13]

Differential Diagnosis — function versus threat versus overlap

Split stable claudication (exercise-first, function-driven) from CLTI rest pain or tissue loss beyond 2 weeks (urgent staging and revascularisation) from the diabetic foot ulcer (arterial assessment first, then the IWGDF diagnosis-prognosis-treatment structure).^[16][4][19] Split atherosclerotic CLTI from the excluded mimics — venous, traumatic, embolic and nonatherosclerotic disease sit outside the GVG syndrome and its trials.^[4] Split the threatened limb that needs a vein (average risk, advanced threat, complex anatomy) from the one that needs a wire (simpler anatomy, intermediate threat, high patient risk) before booking the list.^[4] Split the claudicant who needs metres (exercise, with stenting or cilostazol as adjuncts) from the CLTI leg that needs perfusion (revascularisation plus best medical therapy).^[14][17][4]

Name the category aloud before ordering the scan — the viva rewards the candidate who separates what function decides from what only threat, anatomy or conduit decides.^[4][5]

Clinical & Bedside Assessment — pressures, staging and honest metres

Anchor the diagnosis on ABI of 0.90 or below as the community-study definition, then require objective haemodynamics for CLTI with toe pressures as the preferred measure.^[1][4] Stage the limb by WIfI — wound, ischaemia and infection together — because perfusion alone misleads, especially in diabetes.^[5] Stage the arteries by GLASS and the decision by PLAN, checking vein availability the way BEST-CLI did: single-segment great saphenous vein present or not determines which trial result applies to your patient.^[4][8] Measure claudication honestly on walking distance: exercise adds about 82 m pain-free and 120 m maximum by Cochrane pooling, supervised programmes add minutes on the treadmill by CLEVER, and cilostazol adds about 26 m initial and 40 m absolute at the price of headache — quote metres, never adjectives.^[16][14][17] State the haemodynamic honesty the examiner probes: exercise does not move ABI, so the better walk is function, not fixed arteries.^[16]

Investigations — ABI to define, toe pressures to stage, anatomy to plan

Define PAD with ABI at or below 0.90 in the community-study sense, and assess CLTI with objective haemodynamics led by toe pressures.^[1][4] Run the diabetic-foot diagnostic lane by the IWGDF structure — five recommendations for diagnosing PAD with and without ulcer or gangrene — rather than inventing your own workup.^[19] Map the target artery path for GLASS staging before choosing open versus endo, because anatomic complexity is an independent decision axis.^[4] State the honesty the examiner probes: no keeper abstract supplies duplex velocities, CTA stenosis percentages or angiosome maps, so report named-trial anatomy and vascular-surgical judgement rather than invented imaging cutoffs.

Management — Claudication: exercise first, stent durable, cilostazol modest

Give Cochrane exercise exactly: 32 trials with 1835 participants of stable leg pain — pain-free distance up 82.11 m and maximum distance up 120.36 m, both high-quality evidence, with no ABI, mortality or amputation signal and benefits seen up to two years.^[16] Give CLEVER exactly: 111 aortoiliac patients to optimal medical care with or without supervised exercise or stenting — at 18 months peak walking time gained 5.0 minutes with exercise and 3.2 with stenting against 0.2 with medical care alone, exercise versus stenting not significantly different, and both durable on function and quality of life.^[14] Give ERASE long-term exactly: 106 combination versus 106 exercise-only patients followed a median 5.4 years — the 1-year walking advantage of adding endovascular revascularisation fades to a nonsignificant 53 m at 5 years, exercise-only carries 2.50-fold hazard of a later revascularisation, yet lifetime totals run 65 versus 149 procedures in favour of exercise-only.^[15] Give cilostazol exactly: 16 double-blind trials with 3972 participants — initial distance up 26.49 m and absolute distance up 39.57 m, headache odds 2.83, and no conclusions possible on revascularisation, amputation or cardiovascular events.^[17]

The resolution is the viva sentence: prescribe supervised exercise as the durable first line that also defers procedures; add stenting for aortoiliac disease where disease-specific quality of life matters; add cilostazol for metres with headache honesty — and never promise a fixed artery.^[16][14][17]

Management — CLTI revascularisation: three trials, conduit decides

Give BASIL-1 exactly: 452 patients with severe limb ischaemia from infra-inguinal disease across 27 UK hospitals, surgery-first versus angioplasty-first — amputation-free survival similar (unadjusted HR 1.07, adjusted 0.73), quality of life tied, and surgery about one-third costlier in year one.^[6] Give BASIL-2 exactly, because this is the infrapopliteal trial: 345 patients needing an infrapopliteal with or without proximal infra-inguinal procedure, vein-bypass-first versus best-endo-first — major amputation or death 63 versus 53% (adjusted HR 1.35, p=0.037), driven by deaths at 53 versus 45% (HR 1.37), mostly cardiovascular and respiratory.^[7] Give BEST-CLI exactly, because this is the conduit trial: 1830 patients with infrainguinal disease in two cohorts — adequate single-segment saphenous vein (cohort 1) gives MALE-or-death at 42.6 versus 57.4% favouring surgery (HR 0.68, p < 0.001) over 2.7 years, while alternative conduit (cohort 2) ties at HR 0.79 over 1.6 years.^[8] Give the patency synthesis exactly: 44 studies with 8602 infrainguinal CLTI patients — vein grafts lead infrapopliteal patency at 87% primary and 94% secondary at 1 year (78% and 87% at 2 years), prosthetic grafts run markedly inferior below the knee, drug-eluting stents beat bare metal 73 versus 50% at 1 year in focal tibial disease, and 2-year survival, amputation and amputation-free survival otherwise run broadly similar between endo and vein.^[20]

The surgical resolution: offer vein bypass where good saphenous vein, average risk and complex anatomy meet advanced threat — BEST-CLI's winning ground; offer endo-first where disease is mandatorily infrapopliteal, threat intermediate, or patient risk high — BASIL-2's winning ground; and never average the two into a universal winner.^[8][7][4]

Management — Antithrombotic: clopidogrel over aspirin, rivaroxaban after revascularisation, dual therapy for prosthetic grafts

Give CAPRIE exactly: 19,185 atherosclerotic patients over 3 years with mean 1.91-year follow-up — clopidogrel beats aspirin 325 mg on ischaemic stroke, MI or vascular death at 5.32 versus 5.83% annually, relative-risk reduction 8.7% (p=0.043).^[12] Give EUCLID exactly: 13,885 symptomatic PAD patients to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily — primary endpoint 10.8 versus 10.6% (HR 1.02, tied), acute limb ischaemia 1.7% in both arms, major bleeding 1.6% in both — ticagrelor is not superior to clopidogrel here.^[11] Give VOYAGER exactly: 6564 post-revascularisation patients to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone — primary composite 17.3 versus 19.9% at 3 years (HR 0.85, p=0.009), TIMI major bleeding tied at 2.65 versus 1.87% (p=0.07), ISTH major bleeding higher at 5.94 versus 4.06% (p=0.007).^[9] Give the burden framing exactly: 4714 total first and subsequent vascular events behind the first-event analysis, with rivaroxaban avoiding an estimated 4.4 primary and 12.5 vascular events per 100 participants over 3 years.^[10] Give COMPASS-PAD exactly: 6391 PAD patients where MALE means severe limb ischaemia needing intervention or major amputation — rivaroxaban plus aspirin cuts MALE by 43% and total vascular amputations by 58%, which matters because the post-MALE year amputates 1 in 5 and kills 1 in 12.^[13] Give CASPAR exactly: 851 below-knee bypasses to clopidogrel plus aspirin or aspirin alone — overall tied (HR 0.98), but prosthetic grafts gain (HR 0.65, p=0.025) while venous grafts do not (HR 1.25), interaction p=0.008.^[18]

The prescribing resolution: single antiplatelet with a clopidogrel flavour by CAPRIE and EUCLID; add vascular-dose rivaroxaban after lower-limb revascularisation by VOYAGER with ISTH-bleed counselling; upgrade prosthetic below-knee grafts to dual therapy by CASPAR — and layer antithrombotic, lipid-lowering, antihypertensive and glycaemic agents with smoking, diet, exercise and foot-care counselling for every CLTI patient by GVG.^{[12][11][9][18][4]}

Management — Diabetic foot with PAD: the IWGDF lane

Assume the overlap: approximately half of diabetic foot ulcers carry PAD with raised limb and cardiovascular risk, so arterial assessment is mandatory, not optional.^[19] Work the IWGDF structure — five recommendations for diagnosis, five for prognosis of healing and amputation, fifteen for treatment covering prioritisation, procedure choice and post-surgical care — rather than improvising.^[19] Revascularise by the same PLAN and conduit logic as non-diabetic CLTI, and state the non-revascularisation honesty: spinal stimulation, pneumatic compression, prostanoids and hyperbaric oxygen are unestablished, and cell or gene therapy belongs only inside rigorous randomised trials.^[4]

Complications & Pitfalls — the six traps

The perfusion-only trap — staging by pulses or ABI while ignoring wound and infection, when WIfI exists precisely because perfusion alone misleads in diabetic limbs.^[5][19] The universal-winner trap — quoting BEST-CLI for an infrapopliteal leg without vein or BASIL-2 for an aortoiliac claudicant; the trials enrolled different legs, so match population to patient.^[8][7] The prosthetic-vein equivalence trap — treating a below-knee prosthetic graft like vein when patency and limb loss run markedly inferior and dual therapy only partly rescues it.^[20][18] The claudication-intervention trap — stenting or bypassing stable claudication first-line when exercise matches stenting at 18 months and combination walking gains fade by 5 years.^[14][15][16] The rivaroxaban-free-lunch trap — adding vascular-dose rivaroxaban without ISTH-bleed counselling when major bleeds rise from 4.06 to 5.94%.^[9] The MALE-aftermath trap — discharging the post-MALE patient to routine follow-up when 1 in 5 loses more limb and 1 in 12 dies within the year.^[13]

Prognosis & Disposition — the numbers that set expectations

^{[16] [8] [7] [9] [13] [20]}

Special Populations — surgical contexts that change the emphasis

The diabetic foot carries PAD in about half of ulcers — assess arteries first, prognosticate by the IWGDF five, and revascularise by PLAN rather than defaulting to minor amputation.^[19][4] The high-risk CLTI patient — the BASIL-2 deaths were mostly cardiovascular and respiratory — gets endo-first consideration and full medical optimisation, because the operation is not what kills most of them.^[7][4] The no-vein patient lives in BEST-CLI cohort 2: outcomes tie between surgery and endo, so anatomy, risk and preference carry the decision without a conduit trump card.^[8] The prosthetic-graft leg earns dual antiplatelet therapy by CASPAR where a venous graft does not.^[18] BASIL-2 enrolled 19% women and BEST-CLI populations reflect CLTI demographics — apply PLAN individually rather than quoting sex-specific thresholds this set never verified.

Evidence, Guidelines & Regional Differences — the four stories and who led them

The burden story is Fowkes-to-Song: 202 million in 2010 to 236.62 million aged 25-plus in 2015, settling around 5.56% globally with LMIC majorities — the denominator behind every screening and service claim.^[1][2] The staging story is Mills-to-Conte: WIfI replaces the two-group habit, then GVG adds toe-pressure-led haemodynamics, PLAN decision axes and GLASS anatomy.^[5][4] The revascularisation story is Adam-to-Bradbury-to-Farber: BASIL-1 ties surgery and angioplasty, BASIL-2 favours endo-first in infrapopliteal disease, BEST-CLI favours surgery with good vein — level-1 evidence that splits by anatomy and conduit, exactly as GVG's pending-evidence note anticipated.^[6][7][8][4] The antithrombotic story is CAPRIE-to-EUCLID-to-VOYAGER-to-COMPASS: clopidogrel over aspirin, ticagrelor not over clopidogrel, vascular-dose rivaroxaban after revascularisation and for MALE prevention, dual therapy for prosthetic grafts.^{[12][11][9][13][18]} The current container is the 2024 multisociety PAD guideline across asymptomatic, chronic symptomatic, CLTI and acute limb ischaemia subsets; regional drug availability and service patterns vary, so name the source body beside every protocol claim.^[3]

Exam Pearls — the one-liners that score

• PAD is ABI 0.90 or below; CLTI is PAD plus rest pain, gangrene or ulcer beyond 2 weeks — continuum, not threshold.^[1][4]
• WIfI stages the limb, GLASS the arteries, PLAN the decision.^[5][4]
• Exercise first for claudication: +82 m pain-free, +120 m max, ABI unchanged.^[16]
• CLEVER at 18 months: exercise 5.0 min, stent 3.2 min, medical care 0.2 min — exercise versus stent tied.^[14]
• ERASE at 5 years: 53 m nonsignificant; exercise-only means more later procedures but fewer lifetime totals (65 vs 149).^[15]
• Cilostazol: +26 m initial, +40 m absolute, headache odds 2.83.^[17]
• BEST-CLI with vein: HR 0.68 surgery; without vein: HR 0.79 tied.^[8]
• BASIL-2 infrapopliteal: HR 1.35 endo-first, death-driven.^[7]
• Vein infrapopliteal patency 87/78% at 1/2 years; prosthetic inferior below knee; DES 73 vs BMS 50%.^[20]
• VOYAGER: riva 2.5 mg twice daily plus aspirin, HR 0.85, TIMI tied, ISTH up.^[9]
• Post-MALE year: 20.5% amputated, 8.3% dead — rivaroxaban plus aspirin cuts MALE 43%.^[13]
• Half of diabetic foot ulcers carry PAD — assess arteries in every ulcer.^[19]

Revision summary

Claudication is function: exercise first by Cochrane (+82/+120 m), stenting durable per CLEVER, cilostazol modest with headache. CLTI is threat: define by the 2-week line, stage limb-artery-decision by WIfI-GLASS-PLAN, revascularise by conduit — vein bypass where good vein exists (BEST-CLI HR 0.68), endo-first where disease is infrapopliteal (BASIL-2 HR 1.35). Protect every leg medically: clopidogrel-flavoured single therapy, vascular-dose rivaroxaban after revascularisation with bleed honesty, dual therapy for prosthetic grafts. Special-case the diabetic foot and the post-MALE year.^{[16][4][8][7][9][18][13][19]}

References21ShowHide

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