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Despite recent achievements in secondary cardiovascular prevention, the risk of further events in patients with chronic coronary syndromes (CCS) remains elevated. Highest risk is seen in patients with recurrent events, comorbidities or multisite atherosclerosis. Optimising antithrombotic strategies in this setting may significantly improve outcomes. The higher the baseline risk, the higher the absolute event reduction with approaches using combined antithrombotic treatments. Tailoring such strategies to the individual patient risk appears crucial to achieve net benefit (i.e., substantial ischaemic event prevention at a limited cost in terms of bleeding). This paper focuses on antithrombotic and non-pharmacological approaches to secondary cardiovascular disease prevention in CCS. In particular, we critically review current evidence on the use of dual antithrombotic therapy, including the newest approach of aspirin plus low-dose anticoagulation and its net clinical outcome according to baseline risk.