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............................................................... source (e.g. embolic stroke of undetermined cause), neither dabigatran nor rivaroxaban are better than aspirin.756,757

Recommendations for BP and lipid management are congruent to the general recommendations outlined in sections 4.6 and 4.7.4. In patients with either ischaemic or haemorrhagic cerebrovascular disease who have a BP of 140/90 mmHg or higher, lowering BP reduces the risk of recurrent stroke.758,759 Optimal BP targets in these patients are uncertain, as is the optimal drug regimen.760 Most evidence is available for ACE inhibitors, ARBs, and diuretics. Comorbidities may guide the choice of antihypertensive agent. In patients with recent lacunar stroke, the target SBP is <130 mmHg.761 In patients with stroke (ischaemic or haemorrhagic) or TIA with an LDL-C level of 100 - 190 mg/dL, atorvastatin 80 mg/day reduced the overall incidence of strokes and CV events.762 A recent trial supported an LDL-C target of <1.8 mmol/L (70 mg/dL).508 Evidence of cerebrovascular lesions (e.g. white matter hyperintensities, lacunes, non-lacunar ischaemia) in the absence of any stroke history is a relatively common finding at neuroimaging, especially in older patients. Silent cerebrovascular disease is a marker of increased risk of stroke.763,764 Arterial hypertension, DM, and cigarette smoking contribute to these lesions and should be attended to. There are no studies addressing the best treatment options for silent cerebral ischaemia.765 6.4 Lower extremity artery disease

Symptomatic or asymptomatic LEAD (ABI <_0.90) is associated with a doubling of the 10-year rate of coronary events, CV mortality, and total mortality.125 Within 5 years of LEAD diagnosis, 20% develop AMI or stroke, and mortality is 1015%.767 All LEAD patients require lifestyle improvement and pharmacological therapy. Smoking cessation increases walking distance and lowers amputation risk.2 In patients with DM, glycaemic control improves limb outcomes.768 Statins provide modest improvements in walking distance, and lower the risk of adverse limb events.769,770 Combining a statin with ezetimibe771 or a PCSK9 inhibitor also has beneficial effects.772 Platelet inhibitors are used to prevent limb-related and general CV events. The optimal antiplatelet strategy remains unclear.773 DAPT is currently recommended only after intervention (irrespective of the stent type) for at least 1 month. In the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, low-dose rivaroxaban added to aspirin in CVD patients with an ABI <0.90 reduced not only ASCVD events, but also major adverse limb events, including amputation (HR 0.54),

Recommendations for patients with cerebrovascular disease

Recommendations Classa Levelb

In patients with a cerebrovascular event, improvement of lifestyle factors in addition to appropriate pharmacological management is recommended.732,733,741 I A In patients with ischaemic stroke or TIA, prevention with antithrombotics is recommended; choice of antithrombotic depends on the mechanism of event. Use of an antiplatelet is recommended for patients with non-cardioembolic ischaemic stroke or TIA, and use of an anticoagulant is recommended in patients with cardioembolic ischaemic stroke or TIA.732,741 I A In patients with non-cardioembolic ischaemic stroke or TIA, prevention with aspirin only, or dipyridamole plus aspirin, or clopidogrel alone is recommended.620,743745 I A In patients with minor ischaemic strokec or TIA, DAPT with aspirin and clopidogrel or with aspirin and ticagrelor, for 3 weeks after the acute event should be considered.750,751,755 IIa A In patients with stroke or TIA who have BP of 140/90 mmHg or higher, BP lowering is recommended.757,766 I A

BP = blood pressure; DAPT = dual antiplatelet therapy; TIA = transient ischaemic attack. aClass of recommendation. bLevel of evidence. cMinor ischaemic stroke defined as score at National Institutes of Health Stroke Scale <_3, or <_5 depending on the trial. ESC 2021 Recommendations for patients with lower extremity artery disease: best medical therapy

Recommendations Classa Levelb

Smoking cessation is recommended in all patients with LEAD.29,781 I B Healthy diet and PA are recommended for all patients with LEAD. I C In patients with intermittent claudication:  Supervised exercise training is recommended782784 I A  Non-supervised exercise training is recommended when supervised exercise training is not feasible or available. I C Antiplatelet therapy is recommended in patients with symptomatic LEAD.c I C In patients with LEAD and hypertension, it is recommended to control BP at <140/90 mmHg.776,785,786 I A In patients with LEAD and DM, strict glycaemic control is recommended.768 I A ACE inhibitors or ARBs should be considered as first-line therapy in patients with PAD and hypertension.d 575,787 IIa B In patients with DM and chronic symptomatic LEAD without high bleeding risk, a combination of low-dose rivaroxaban (2.5 mg b.i.d.) and aspirin (100 mg o.d.) may be considered.774 IIb B

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; b.i.d. = bis in die (twice a day); BP = blood pressure; CCB = calcium channel blocker; DM = diabetes mellitus; LEAD = lower extremity artery disease; o.d. = omni die (once a day); PA = physical activity; PAD = peripheral artery disease. aClass of recommendation. bLevel of evidence. cEvidence is not available for all sites. When evidence is available, recommendations specific for the vascular site are presented in corresponding sections. dCCBs should be proposed in black individuals. ESC 2021

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