PROMISE-Lp(a)

Atherosclerotic cardiovascular disease, especially ischemic heart disease, remains one of the leading causes of morbidity and mortality worldwide. To reduce cardiovascular risk, several secondary prevention strategies are recommended. Conversely, current evidence on the optimal treatment for primary prevention is lacking in patients who show evidence of atherosclerosis but have not yet developed established ischemic heart disease. A subset of patients at high cardiovascular risk and with a greater likelihood of disease progression is identified by elevated lipoprotein(a) levels. Currently, these patients receive lipid-lowering therapy with statins, ezetimibe or additional drugs as needed; in addition, they also receive antiplatelet therapy, with aspirin being the standard choice. Waiting for specific therapies to reduce lipoprotein(a) levels and in the absence of established risk mitigation strategies for primary prevention, the PROMISE-Lp(a) study aims to investigate a multimodal therapeutic approach for high-risk patients with early-stage atherosclerotic disease. Elevated lipoprotein (a) levels are associated with higher thrombotic and infllammatory risks. A total of 207 patients with elevated lipoprotein(a) levels and nonobstructive coronary artery disease at coronary computed tomography angiography (CCTA) will be randomized with a 2x2 factorial design to: Colchicine vs. no colchicine; Ticagrelor vs. aspirin. The study hypothesis is that colchicine may exert anti-inflammatory effects and promote the stabilization of coronary plaques identified at the screening CCTA. A follow-up CCTA will be performed after one year to assess disease progression and plaque characteristics, with a particular focus on local inflammation measured by fat attenuation index (FAI). Another study hypothesis is that ticagrelor may reduce the thrombotic burden, as represented by the soluble CD40 ligand (sCD40L), which is released by activated platelets and indicates atherosclerotic disease progression and plaque destabilization (i.e., platelet aggregation and thrombosis). The co-primary endpoints of the study are the difference in FAI between baseline and 1-year CCTA and the difference in sCD40L levels between baseline and 1-year follow-up.