Effect of PCSK9 inhibitor usage on coronary endothelial dysfunction in patients with hypercholesterolemia after coronary stenting: The CuVIC-2 trial.

Background: The effects of evolocumab on coronary endothelial dysfunction (CED), a hallmark of atherogenesis, are unknown. The aim of this study was to investigate whether evolocumab, in combination with high-dose statins, could ameliorate CED in patients who underwent coronary stenting.

Methods: The CuVIC-2 trial was a multicenter randomized controlled trial. CED was defined as intracoronary acetylcholine (ACh)-induced contractile responses with signs of myocardial ischemia. We originally intended to enroll 160 participants but altered the study design due to the COVID-19 pandemic and then recruited 41 participants. The revised primary endpoint was the coronary contraction rate in response to ACh assessed in a core laboratory, ensuring a statistical power of over 80 % using the mixed model for repeated measures.

Results: The evolocumab in combination with high-dose statins with or without ezetimibe (EV + S) group included 19 males and 4 females aged 62 ± 13 years. The high-dose statins with or without ezetimibe (S) group included 13 males and 5 females aged 64 ± 11 years. Compared with the S group, the EV + S group presented a significantly greater decrease in low-density lipoprotein cholesterol at 28 weeks; 83 ± 17 to 20 ± 16 mg/dL (-76 % from the baseline) in the EV + S group and 88 ± 16 to 81 ± 20 mg/dL (-7 % from the baseline) in the S group (p < 0.0001). At 28 weeks, there was no difference between the two groups in terms of the coronary artery constriction rate across all doses [mean difference: 4.8 % (95 % CI: -13.6 to 23.2); p = 0.6].

Conclusions: Amelioration of CED by evolocumab was not observed in this trial with several limitations.