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Pharmacotherapy to decrease walking impairment Verapamil,516 statins,517,518 antiplatelet agents, and prostanoids (prostaglandins I2 and E1)519 can alleviate walking impairment in patients with symptomatic PAD. However, drugs like cilostazol, naftidrofuryl, pentoxifylline, buflomedil, carnitine, and propionyl-L-carnitine are suggested to increase walking distance in patients with IC without impacting CV health.339,520 Their objective benefit is generally limited, ranging from mild to moderate, with considerable variability.339 The additional benefit of these drugs alongside antithrombotics, antihypertensives, and statins remains unknown. Cilostazol, a phosphodiesterase type III inhibitor, improved MWD compared with placebo and pentoxifylline.520–522 In a Cochrane analysis, 100 mg twice daily increased MWD by 76%,521 while another review reported a 25% average improvement.520 Cilostazol also has antiplatelet effects, requiring cautious combination with other anticoagulant and antiplatelet treatments.522 Notably, it increases bleeding complications.523 Naftidrofuryl oxalate, tested for IC,524 demonstrated a 74% average increase in MWD and improved HRQoL.524,525 In a systematic review, the average MWD improvement was 60% compared with placebo.520 However, inconsistent results for other medications, such as prostanoids, pentoxifylline, L-arginine, buflomedil, or Gingko biloba, preclude their recommendation for patients with IC.519,526,527

8.1.1.2.3 Aorto-iliac lesion revascularization. Aorto-iliac lesions can

be treated by either an endovascular or a surgical approach according to the lesion morphology and patient risk. Long-term patency with a low risk of complications can be achieved by balloon angioplasty with or without stenting in external iliac arteries or primary stenting in common iliac arteries.528 A meta-analysis evaluated outcomes of open surgery vs. an endovascular approach in aorto-iliac lesions (TASC II C-D) and found that short-term morbidity and mortality favours the endovascular approach, but early and mid-term primary patency favours open surgery; however, secondary patency is comparable in all groups.

Treatment with combination rivaroxaban (2.5 mg b.i.d.) and aspirin (100 mg o.d.) should be considered for patients with PAD and non-high bleeding risk following lower-limb revascularization.490,505 IIa B Use of antiplatelet therapy with clopidogrel alone (75 mg o.d.) may be considered over aspirin to reduce MI, stroke, and vascular death.493,494 IIb B Aspirin (75–100 mg) for primary prevention may be considered in patients with asymptomatic PAD and DM, in the absence of contraindications.419,487 IIb A DAPT for at least 1 month after revascularization may be considered to reduce limb events.500,501,503,513,514 IIb B Long-term DAPT in patients with PAD is not recommended.489 III A Oral anticoagulant monotherapy for PAD (unless for another indication) is not recommended.515 III A The routine use of ticagrelor in patients with PAD is not recommended.495 III A It is not recommended to systematically treat patients with asymptomatic PAD without any sign of clinically relevant ASCVD with antiplatelet drugs.485 III B © ESC 2024

ASCVD, atherosclerotic cardiovascular disease; DAPT, dual antiplatelet therapy; DM, diabetes mellitus; MACE, major adverse cardiovascular events; MI, myocardial infarction; o.d., once daily; PAD, peripheral arterial disease. aClass of recommendation. bLevel of evidence. cHigh ischaemic risk: previous amputation, critical limb threatening ischaemia, previous revascularization, high-risk comorbidities (heart failure, diabetes, vascular disease in two or more vascular beds), eGFR <60 mL/min/1.73 m2.498 dHigh bleeding risk: dialysis or renal impairment GFR <15 mL/min/1.73 m2, acute coronary syndrome <30 days, history of intracranial haemorrhage, stroke or TIA, active or clinically significant bleeding.

Patients with chronic symptomatic PAD

Assess risk level at every follow-up

High-risk limb presentation or high-risk comorbiditiesa without high bleeding risk

Non high-risk limb presentation

or high-risk comorbiditiesa

Single antiplatelet therapy

(ASA or clopidogrel)

(Class I) ASA and 2.5 mg rivaroxaban b.i.d.

(Class IIa) Single OAC monotherapy

(Class IIb)

Patients requiring long-term anticoagulation

Figure 14 Long-term antithrombotic therapy in patients with symptomatic peripheral arterial disease. b.i.d., twice daily; OAC, oral anticoagulant; PAD, peripheral arterial disease; ASA, aspirin aHigh-risk limb presentation: previous amputation, chronic limb-threatening ischaemia, previous revascularization, high-risk comorbidities: heart failure, diabetes, vascular disease in two or more vascular beds, moderate kidney dysfunction; eGFR <60 mL/min/1.73 m2.

ESC Guidelines                                                                                                                                                                                          3583

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