The addition of evolocumab vs ezetimibe to statin therapy for coronary plaque regression and sd-LDL reduction in patients with ultrahigh-risk ASCVD.

BACKGROUND

Despite achieving target low-density lipoprotein cholesterol (LDL-C) levels, patients with ultrahigh-risk atherosclerotic cardiovascular disease (ASCVD) continue to experience substantial residual cardiovascular risk. Small dense LDL (sd-LDL) is increasingly recognized as a key atherogenic factor.

OBJECTIVE

To compare the efficacy of adding evolocumab vs ezetimibe to statin therapy in promoting coronary plaque regression, and to evaluate the predictive value of sd-LDL reduction in patients with ultrahigh-risk ASCVD.

METHODS

In this prospective, randomized, open-label, single-center trial, 422 patients with ultrahigh-risk ASCVD and LDL-C levels ≥1.4 mmol/L despite moderate-intensity statin therapy were enrolled. Participants were randomly assigned (1:1) to receive either ezetimibe (10 mg daily) or evolocumab (140 mg every 2 weeks) in addition to statins. The primary endpoints were changes in percent diameter stenosis and the rate of plaque regression over 12 months, assessed by coronary angiography or coronary computed tomography angiography.

RESULTS

After 12 months, the evolocumab group showed significantly greater reductions in both LDL-C and sd-LDL compared to the ezetimibe group (P < .001). Coronary plaque regression occurred in 35.6% of patients in the evolocumab group vs 10.5% in the ezetimibe group (P < .001). Multivariable logistic regression identified the percentage reductions in both sd-LDL (adjusted odds ratio [OR]: 0.54; 95% CI: 0.32-0.86; P = .014) and LDL-C (OR: 0.63; 95% CI: 0.47-0.85; P = .002) as independent predictors of plaque regression. Discordance analysis revealed that achieving sd-LDL targets was associated with higher regression rates, regardless of LDL-C levels. A nomogram combining sd-LDL changes and baseline clinical variables demonstrated moderate predictive accuracy (area under the curve = 0.669).

CONCLUSION

In patients with ultrahigh-risk ASCVD, evolocumab was more effective than ezetimibe in promoting coronary plaque regression. Moreover, reductions in sd-LDL were strongly associated with plaque regression alongside reductions in LDL-C. These findings underscore the importance of targeting sd-LDL to reduce residual cardiovascular risk.