Alirocumab reduces total coronary plaque burden in patients with familial hypercholesterolaemia and no previous clinical atherosclerotic disease

Abstract Background It is well known that statins, ezetimibe and other lipid lowering treatments such as Evolocumab (PCSK9-Inhibitor) reduce cardiovascular events by decreasing LDL-cholesterol (LDL-C) levels and slowing the progression of coronary atherosclerosis. Nevertheless, cardiovascular (CV) risk remains. Alirocumab, a PCSK9 inhibitor has demonstrated a reduction in cardiovascular events but its relationship with coronary atherosclerosis reduction has not been adequately demonstrated. Purpose The ARCHITECT trial sought to determine whether Alirocumab 150 mg/2 weeks is able to stop or reverse coronary atherosclerosis progression, by assessing coronary plaque burden (CPB) by serial multidetector computed tomography (MDCT). Methods A total of 104 patients with molecularly characterized heterozygous familial hypercholesterolaemia (FH) without clinical cardiovascular disease were enrolled in this trial. Patients had to have CPB >30% as documented by MDCT, be on maximum tolerated statin therapy with or without ezetimibe and LDL-C >100 mg/dL. Patients underwent a MDCT at enrollment and after 18-month treatment with alirocumab and they were analyzed by means of QAngio CT (Medis medical imaging system, the Netherlans). The pre-specified primary endpoint was change in CPB. Results Median age was 53.3 (46.2–59.4) years (54, 51.9% woman). Median LDL-cholesterol was 138.9 mg/dL. There was a significant reduction in the primary endpoint as Alirocumab reduced CPB from 34.6 (32.9–36.8)% to 30.4 (27.4–33.4)%. Significant reductions in LDL-C (67%) and atherosclerotic plaque volume were also found. Plaque regression as estimated by CPB was found in 91 (87.5%) patients. Main resuts may be found in figure 1. Conclusions Alirocumab demonstrated significant regression of CPB on MDCT over 18 months. ARCHITECT provides crucial mechanistic clues on coronary plaque behavior under the use of Alirocumab and its results could link and explain ODYSSEY-OUTCOMES results. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi