Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease

Inclusion Criteria: * Individuals aged ≥ 45 years AND * Signature of the Informed Consent Form (ICF) AND at least one of the following criteria: * Previous atherothrombotic cardiovascular event (acute coronary syndrome, ischemic stroke, high-risk transient ischemic stroke, acute limb ischemia/arterial occlusion, or non-traumatic limb amputation) AND/OR * Previous arterial revascularization (percutaneous, surgical, and/or hybrid) OR * Diagnosis of significant atherosclerotic disease with ≥ 50% obstruction in any arterial territory (coronary, cerebrovascular, or peripheral), in the absence of a prior cardiovascular event or arterial revascularization. Exclusion Criteria: * Pregnant or lactating women; * Women of childbearing age who do not use any form of contraception; * Known history of chronic kidney disease, stage ≥ 4 (estimated glomerular filtration rate ≤ 30 mL/min, if available); * Known history of cirrhosis or severe liver disease (e.g., transaminase levels \> 3 times the upper limit of normal, if available); * Known history of inflammatory muscle disease (e.g., dermatomyositis or polymyositis) or creatine phosphokinase (CPK) levels \> 3 times the upper limit of normal, if available); * Known history of moderate or severe valvular heart disease with anticipated need for valvular intervention within the next 12 months; * Planned arterial revascularization (inclusion is possible 30 days after completion of all planned procedures); * Left ventricular ejection fraction ≤40% (with the exception of patients with documented intolerance to ACE inhibitors and/or sacubitril/valsartan, who remain eligible for study enrollment); * Heart failure with functional class ≥ III according to the New York Heart Association (NYHA), regardless of left ventricular ejection fraction; * Blood pressure \< 120/80 mmHg in the absence of antihypertensive therapy; * Life expectancy ≤ 12 months; * Acute arterial event (acute coronary syndrome, non-cardioembolic ischemic stroke, acute limb ischemia) in the past 30 days; * Substance abuse/alcoholism; * Psychiatric and/or neurodegenerative disorder limiting self-care capacity; * Concurrent participation in another randomized clinical trial; * Contraindication to any component of the polypill; * Current or planned use of oral anticoagulant therapy within the next 12 months (except rivaroxaban 2.5 mg twice daily for patients with peripheral artery disease); * High risk of bleeding (e.g., but not limited to: blood dyscrasias, hemophilia, previous gastrointestinal or central nervous system bleeding); * Contraindication to colchicine; * Current use of colchicine.