Jonathan Los, Frans B. Mensink, Mohamed M Reda Abdelaziz Morsy, Kensuke Nishimiya, Rohit M. Oemrawsingh, Alexander J.J. Ijsselmuiden, Martijn Meuwissen, Jin M. Cheng, Himanshu Rai, Tim J.F ten Cate, Cyril Camaro, Peter Damman, L X Van Nunen, A L Dimitriu-Leen, Marleen van Wely, Aysun Cetinyurek-Yavuz, R. Byrne, N Van Royen, Robert-Jan M. van Geuns
Abstract Aims The aim of this study was to evaluate the short-term potential of very-high-intensity lipid-lowering therapy on lesion-level atheroma burden. Methods The investigator-initiated, double-blind, placebo-controlled FITTER trial (enrollment November 2020 to August 2023) randomized patients presenting with acute coronary syndrome (ACS) and relevant non-culprit coronary artery disease (fractional flow reserve: 0.67–0.85) to receive either evolocumab or placebo for 12 weeks in addition to high-intensity statin therapy to evaluate the short-term potential of lipid-lowering therapy on non-culprit plaque features. Present lesion-level analysis assessed the effects on coronary segments with advanced atherosclerotic plaque characteristics with increased cardiovascular risk and includes all patients who underwent successful serial intravascular ultrasound-near-infrared spectroscopy (IVUS-NIRS) imaging and with presence of IVUS-derived atherosclerotic lesions. Results A total of 126 lesions were identified in 85 patients (mean age 65.1 ± 8.3, 18.8% female), of which 65 lesions were found in the evolocumab group (44 patients) and 61 in the placebo group (41 patients). Compared to placebo, patients treated with evolocumab did not demonstrate significant reductions in maximum lipid core index within any 4 mm segment (maxLCBI 4mm , between-group difference, −9.6 [95% CI, −52.8 to 33.6]; p = 0.7) or percent atheroma volume (PAV, between-group difference, 1.0% [95% CI, −1.3 to 3.2]; p = 0.4). However, an overall reduction in maxLCBI 4mm (overall change, −54.2 [95% CI, −89.6 to −18.7]; p = 0.003) and PAV (overall change, −2.0% [95% CI, −3.9 to −0.1]; p = 0.04) was observed. Conclusions Compared with placebo, the addition of evolocumab did not yield incremental improvements in lesion-level atheroma burden in the first 12 weeks after ACS. However, in the pooled analysis, significant short-term reductions in atheroma volume and plaque lipid content were observed. Trial registration number: clinicaltrials.gov NCT04141579.