Achieved levels of apolipoprotein B and plaque composition after acute coronary syndromes: Insights from HUYGENS

Background and aims: Addition of the PCSK9 inhibitor, evolocumab, to statin therapy promoted coronary plaque stabilization after an acute coronary syndrome. While apolipoprotein B (ApoB) has been proposed as a goal for lipid-lowering therapy in the prevention of cardiovascular disease, its association with plaque stability has not been studied. Methods: The High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS) used serial optical coherence tomography to assess coronary plaque phenotypes in patients with non-ST elevation myocardial infarction treated with evolocumab plus statin or placebo plus statin for 52 weeks. Changes in plaque composition were studied in patients according to achievement of a goal ApoB level <65 mg/dL. Results: Of 112 patients, 67 (59.8 %) achieved the ApoB goal and had lower ApoB values at follow-up compared with those not at goal (37.1 +/- 15.0 vs 92.7 +/- 19.4 mg/dL, P < 0.001). Patients achieving the ApoB goal demonstrated a greater increase in minimum fibrous cap thickness (+44.6 +/- 36.0 vs +24.9 +/- 38.1 mu m, P = 0.007) and a more pronounced decrease in lipid arc (-57.8 +/- 52.8 vs -27.0 +/- 59.2 degrees, P = 0.005) at follow-up, compared with those who did not achieve the ApoB goal. At follow-up, thin-cap fibroatheroma (TCFA) was less prevalent among patients achieving the ApoB goal compared with those not at goal (9.0 vs. 40.0 %, P < 0.001). Multivariate analysis demonstrated that achieving an ApoB <65 mg/dL at follow-up independently associated with the absence of TCFA at follow-up (P = 0.004). Conclusions: Lower achieved ApoB levels associated with evidence of greater plaque stabilization even after controlling for low-density lipoprotein cholesterol levels. This highlights the importance of optimizing ApoB levels for the reduction of cardiovascular risk.