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albeit at the cost of higher major bleeding risk.774 These results, combined with similar benefits of rivaroxaban vs. aspirin monotherapy, suggest a benefit of anticoagulants in LEAD. However, further studies are needed. Optimal antithrombotic therapy is addressed in more detail in the 2017 ESC/European Society for Vascular Surgery (ESVS) Guidelines.775 Importantly, in patients with isolated asymptomatic LEAD (e.g. low ABI), antiplatelet treatment is not recommended.775 Recommendations for BP and lipid management are congruent to the general recommendations outlined in sections 4.6 and 4.7. Hypertension targets are based mainly on INVEST (INternational VErapamil-SR/Trandolapril STudy).776 An SBP below 110120 mmHg may increase CV events in patients with LEAD.776 ACE inhibitors and ARBs reduce CV events in patients with LEAD,575,777 and are preferred (as monotherapy or as part of a combination drug regimen).778 Beta-blockers are not contraindicated in mild-to-moderate LEAD as they do not affect walking capacity or adverse limb events,779 and significantly reduce coronary events.780 Nevertheless, beta-blockers should be carefully considered in critical limb-threatening ischaemia.

6.5 Chronic kidney disease

Severe CKD is associated with a very high risk of CVD and is considered a CAD risk equivalent (see section 3.2). As GFR declines, nontraditional risk factors emerge and non-atherosclerotic CVD event risk increases.204 Trials often exclude patients with eGFR <30 mL/ min/1.73 m2. In patients on dialysis, coronary syndromes may present atypically, and angina equivalents—such as shortness of breath or fatigue—are frequent.788 Standard CVD risk management is effective in patients on dialysis, but unique haemodialysis-specific syndromes (i.e. intradialytic hypotension and myocardial stunning) associated with mortality complicate treatment and modify outcomes. Risk classification of patients with various degrees of CKD is summarized in Table 4. Treatment with a statin or statin/ezetimibe combination is recommended in CKD patients with sufficiently high CVD risk, but not in those treated with kidney replacement therapy. This recommendation is built on evidence from SHARP (Study of Heart and Renal Protection), which demonstrated a reduction of major atherosclerotic events.525 Statins should be dosed according to a moderate-intensity regimen based on limited experience and risks associated with high-intensity regimens.543 Subgroup analysis of a recent study with a PCSK9 inhibitor has shown that the benefits may extend to those with earlier CKD stages (6090 as well as 3060 mL/min/1.73 m2).789 Treatment with an ACE inhibitor or an ARB is recommended in patients with DM, hypertension, and albuminuria. These medications should be titrated to the maximum tolerated dose (Kidney Disease Improving Global Outcomes grading 1B). Individualized HbA1c targets, ranging from 6.5% to <8.0% in patients with DM and non-dialysis-dependent CKD, are recommended in parallel. The role of SGLT2 inhibitors and GLP-1RAs in CKD associated with DM is addressed in section 4.8. Dapagliflozin has shown promising reno- and cardioprotective effects,599 and more studies investigating SGLT2 inhibitors in CKD patients without DM are ongoing.790 Overall, the management of CAD in CKD patients must be informed by the modification of its clinical presentation in CKD, as well as comorbidity and risks of treatment side-effects. Treatment of established risk factors is often suboptimal in patients with CKD. 6.6 Atrial fibrillation

The simple ‘Atrial fibrillation Better Care’ (ABC) holistic pathway (‘A’ = Anticoagulation/Avoid stroke; ‘B’ = Better symptom management; ‘C’ = Cardiovascular and Comorbidity optimization) streamlines integrated care of patients with AF.215 The ABC pathway lowers risk of all-cause death and the composite of stroke, major bleeding, CV death, or first hospitalization,791 and lowers rates of CV events792,793 and health-related costs.794 The ‘C’ component of the ABC pathway refers to identification and management of concomitant diseases, cardiometabolic risk factors, and unhealthy lifestyle factors. Therapy of underlying conditions improves rhythm control in persistent AF and HF.216 In obese patients, weight reduction prevents AF recurrences and symptoms.795802 Given that hypertension precipitates AF, treatment of hypertension is mandatory. Alcohol excess is a risk factor for incident AF,803,804 and abstinence reduced AF recurrences in regular drinkers.798 Many studies have demonstrated beneficial effects of moderate exercise/PA.805807 The incidence of AF appears, however, to be increased in elite athletes, mainly related to endurance sports.808811 Patients should be encouraged to practise moderate-intensity exercise and remain physically active to prevent AF incidence or recurrence, but avoid excessive endurance exercise. CR is a universally recommended programme for patients with ACS and/or revascularization, and for patients with HF.639,640,655 The benefits of EBCR are more uncertain in patients with AF, but CR remains recommended in patients with the aforementioned indications.812 Continuous PAP may improve rhythm control and attenuate AF recurrences in OSA patients.813816 Intensive glycaemic control does not affect the rate of new-onset AF.817 Optimal glycaemic control during the 12 months before AF ablation does, however, reduce AF recurrence after ablation.818 All patients with HF and AF should receive guideline-adherent HF therapy.819

Recommendations in patients with chronic kidney disease: best medical therapya

Recommendations Classb Levelc

Treatment with an ACE inhibitor or an ARB is recommended in patients with DM, hypertension, and albuminuria. These medications should be titrated to the highest approved dose that is tolerated. I B An SGLT2 inhibitor with proven outcome benefits should be considered for the prevention of renal deterioration and mortality in patients with CKD.599 IIa B Combination treatment with ACE inhibitors and ARBs is not recommended. III C

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CKD = chronic kidney disease; DM = diabetes mellitus; SGLT2 = sodium-glucose cotransporter 2. aRecommendations on CKD management in patients with DM are found in section 4.8. bClass of recommendation. cLevel of evidence. ................................................................. ESC 2021 Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026