Summary

Comprehensive update to the 2016 AHA/ACC PAD guideline covering diagnosis and management of lower extremity peripheral artery disease across four clinical subsets: asymptomatic PAD, chronic symptomatic PAD (claudication), chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI). New emphasis on PAD-related risk amplifiers, health disparities, multispecialty team-based care for CLTI, structured exercise (including community/home-based), and incorporation of low-dose rivaroxaban plus aspirin for prevention of MACE/MALE. Reflects evidence from BEST-CLI, BASIL-2, VOYAGER PAD, and COMPASS trials.

Key Recommendations

Diagnose PAD using resting ankle-brachial index (ABI) in patients with history/exam findings suggestive of PAD; use toe-brachial index (TBI) when ABI >1.40 due to noncompressible vessels.
Prescribe single antiplatelet therapy (aspirin or clopidogrel) for patients with symptomatic PAD to reduce MACE; clopidogrel is an acceptable alternative to aspirin.
Add low-dose rivaroxaban 2.5 mg twice daily to low-dose aspirin 81 mg daily in patients with PAD (chronic symptomatic or post-revascularization) without high bleeding risk to reduce MACE and MALE.
Prescribe high-intensity statin therapy for all patients with PAD targeting ≥50% LDL-C reduction; add ezetimibe or PCSK9 inhibitor if LDL-C remains ≥70 mg/dL.
Treat hypertension to BP <130/80 mm Hg; use ACE inhibitors or ARBs as first-line agents in PAD with hypertension.
Use GLP-1 agonists (liraglutide, semaglutide) or SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) in patients with PAD and type 2 diabetes to reduce MACE.
Implement smoking cessation with combined behavioral counseling plus pharmacotherapy (varenicline, bupropion, or nicotine replacement) for all patients with PAD who smoke.
Refer all patients with chronic symptomatic PAD/claudication to supervised exercise therapy (SET) as first-line; structured community/home-based programs are an effective alternative.
Avoid revascularization in asymptomatic PAD; reserve revascularization for functionally limiting claudication unresponsive to GDMT and structured exercise, or for CLTI/ALI.
For CLTI candidates with adequate single-segment great saphenous vein, surgical bypass is preferred over endovascular therapy as initial strategy (per BEST-CLI Cohort 1).
Manage CLTI through a multispecialty care team including revascularization, wound care, podiatry, and infection management; evaluate prior to major amputation except in life-threatening sepsis.
For ALI with viable/threatened limb (Rutherford I/IIa/IIb), initiate IV unfractionated heparin and pursue urgent revascularization (catheter-directed thrombolysis, mechanical thrombectomy, or surgery); amputate primarily for Class III irreversible ischemia.
Use cilostazol to improve claudication symptoms and walking distance; contraindicated in heart failure of any severity.
Perform annual comprehensive foot evaluation and provide patient education on self-foot care; prescribe therapeutic footwear for patients with neuropathy, deformities, or prior ulcer/amputation.

Thresholds & Doses

Resting ABI: ≤0.90 diagnostic of PAD; >1.40 indicates noncompressible vessels (use TBI).
TBI ≤0.70 is abnormal; absolute toe pressure <30 mm Hg reflects severe ischemia.
TcPO2 >30 mm Hg or SPP >40 mm Hg predicts wound healing in CLTI.
ALI defined as symptoms ≤2 weeks; CLTI defined as symptoms >2 weeks.
Skeletal muscle tolerates ischemia ~4-6 hours before irreversible damage.
Rivaroxaban 2.5 mg twice daily + aspirin 81 mg daily for PAD (COMPASS/VOYAGER regimen).
Blood pressure target <130/80 mm Hg in PAD.
LDL-C target <70 mg/dL; high-intensity statins: atorvastatin 40-80 mg or rosuvastatin 20-40 mg.
Hemoglobin A1c targets: <7% generally; <8% associated with lower amputation risk in diabetic foot ulcers.
Supervised exercise therapy: ≥3 sessions/week, 30-45 minutes per session, minimum 12 weeks, walking to moderate-maximum claudication pain.
6-minute walk test used for functional assessment; ABI decrease >0.15 from prior suggests revascularization failure.
PAD screening considered: age ≥65; age 50-64 with risk factors; age <50 with diabetes plus 1 additional risk factor.
Foot inspection frequency by ulcer risk: low-risk annually; moderate-risk every 3-6 months; high-risk every 1-3 months.
Cilostazol assessed for tolerance at 2-4 weeks, benefit at 3-6 months.
Catheter-directed thrombolysis effective for arterial/graft occlusion <14 days duration.

Citations

Top 10 Take-Home Messages — overarching principles including 4 clinical subsets and rivaroxaban 2.5 mg BID + aspirin regimen
Section 2.1, Table 4 — definitions of asymptomatic PAD, chronic symptomatic PAD, CLTI, and ALI with Rutherford classification
Section 3.1 — resting ABI thresholds, TBI use in noncompressible vessels, perfusion measures (TcPO2, SPP)
Section 5.1 — antiplatelet/antithrombotic recommendations including COMPASS and VOYAGER PAD trial evidence
Section 5.2, Table 11 — lipid-lowering with high-intensity statin therapy and LDL-C targets
Section 6, Table 14 — supervised exercise therapy and structured community-based exercise programs
Section 10.2, Table 16 — revascularization strategy for CLTI incorporating BEST-CLI and BASIL-2 results
Section 11, Figure 8 — ALI diagnosis and management algorithm with Rutherford classification and anticoagulation
Section 5.8, Tables 12-13 — preventive foot care, risk factors for ulcers, and comprehensive foot evaluation components