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........................................................................... • The efficacy and safety of aspirin or other antithrombotic therapy in patients without clinical manifestations of CAD—but with atherosclerotic disease identified on imaging, such as CCTA— requires further assessment. • The optimal long-term antithrombotic therapy in patients at high risk of ischaemic events is uncertain. • Clinical studies comparing the efficacy and safety of P2Y12 inhibitors vs. low-dose rivaroxaban or other factor Xa inhibitors, in combination with aspirin, are warranted to determine which subgroups will derive greater clinical benefit with each strategy. Heart failure • For patients with HFpEF, no specific pharmacotherapy or device implantation has been shown to modify the risk of any CV outcome. • Lower dosage of HF treatments in women with HFrEF needs to be addressed, since women were underrepresented in many HF trials. Cerebrovascular disease • The optimal selection of patient for a short course of DAPT. • The optimal antihypertensive regimen and target BP. • The optimal target level of LDL-C. • Optimal treatment for patients with silent cerebrovascular disease. Lower extremity artery disease • The optimal type and potency of antithrombotic therapy in patients with different manifestations of symptomatic or asymptomatic LEAD are partly unclear. Chronic kidney disease • Few CVD trials have a focus on patients with CKD, particularly those with advanced CKD. • Additional prospective studies focusing on diagnosis, prevention, and treatment of CAD and CVD are needed in CKD. Atrial fibrillation • The effects of various CV risk factors and comorbidities in AF. • Optimal treatment of OSA and its effect on AF progression and symptoms. Multimorbidity • The effect of different clusters or combinations of CV and non- CV comorbidities on CV outcomes. • Optimal, pragmatic treatment strategies in patients with CV and non-CV comorbidities, with particular focus on treatment adherence and therapeutic competition. 9 ‘What to do’ and ‘what not to do’ messages from the guidelines Recommendations Classa Levelb Recommendations for cardiovascular disease risk assessment Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor (i.e. family history of premature CVD, FH, CVD risk factors such as smoking, arterial hypertension, DM, raised lipid level, obesity, or comorbidities increasing CVD risk). I C Systematic CVD risk assessment in men <40 years of age and women <50 years of age with no known CV risk factors is not recommended. III C Recommendations for cardiovascular disease risk estimation In apparently healthy people <70 years of age without established ASCVD, DM, CKD, genetic/rarer lipid or BP disorders, estimation of 10-year fatal and non-fatal CVD risk with SCORE2 is recommended. I B In apparently healthy people >_70 years of age without established ASCVD, DM, CKD, genetic/rarer lipid or BP disorder, estimation of 10-year fatal and nonfatal CVD risk with SCORE2-OP is recommended. I B Patients with established CVD and/or DM and/or moderate-to-severe renal disease and/or genetic/rarer lipid or BP disorders are to be considered at high or very high CVD risk. I A A stepwise treatment-intensification approach aiming at intensive risk factor treatment is recommended for apparently healthy people at high or very high CVD risk, as well as patients with established ASCVD and/or DM, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences. I B Treatment of ASCVD risk factors is recommended in apparently healthy people without DM, CKD, genetic/rarer lipid or BP disorders who are at very high risk (SCORE2 >_7.5% for age under 50; SCORE2 >_10% for age 5069; SCORE2-OP >_15% for age >_70 years). I C Recommendation for cardiovascular disease risk communication An informed discussion about CVD risk and treatment benefits tailored to the needs of a patient is recommended. I C Recommendations for risk modifiers The routine collection of other potential modifiers, such as genetic risk scores, circulating or urinary biomarkers, or vascular tests or imaging methods (other than CAC scoring or carotid ultrasound for plaque determination), is not recommended. III B Continued Downloaded from academic.oup.com/eurheartj/article/42/34/3227/6358713 by guest on 07 October 2026