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Randomized Controlled Trial
. 2025 Aug 18;21(16):910-920.
doi: 10.4244/EIJ-D-24-01065.

Changes in non-culprit coronary lesions with PCSK9 inhibitors: the randomised, placebo-controlled FITTER trial

Frans B Mensink  1 , Jonathan Los  1 , Mohamed M Reda Morsy  2 , Rohit M Oemrawsingh  3 , Clemens von Birgelen  4 , Alexander J J Ijsselmuiden  5   6 , Martijn Meuwissen  5 , Jin M Cheng  3   5 , Diederik F van Wijk  7 , Pieter C Smits  8 , Valeria Paradies  8 , Dirk J van Wijk  9 , Himanshu Rai  10   11 , Tim J F Ten Cate  1 , Cyril Camaro  1 , Peter Damman  1 , Lokien X van Nunen  1 , Aukelien C Dimitriu-Leen  1 , Marleen H van Wely  1 , Aysun Cetinyurek-Yavuz  1 , Robert A Byrne  10   11 , Niels van Royen  1 , Robert-Jan M van Geuns  1
Affiliations
Randomized Controlled Trial

Changes in non-culprit coronary lesions with PCSK9 inhibitors: the randomised, placebo-controlled FITTER trial

Frans B Mensink et al. EuroIntervention. .

Abstract

Background: Prolonged lipid-lowering therapy has demonstrated its ability to induce plaque regression and improve the plaque morphology of mild atherosclerotic lesions.

Aims: This trial aimed to assess the short-term effect of evolocumab in addition to high-intensity statin therapy (HIST) on relevant non-culprit coronary artery lesions using fractional flow reserve (FFR) measurements and multimodality intracoronary imaging.

Methods: Patients with an acute coronary syndrome (ACS) and relevant multivessel disease were randomised to receive either evolocumab or placebo for 12 weeks in addition to HIST. Patients underwent serial FFR and intravascular ultrasound (IVUS)-near-infrared spectroscopy imaging of a non-culprit vessel. The primary endpoints were the differences in the change in FFR and in the maximum lipid core burden index within any 4 mm segment (maxLCBI4mm). The secondary endpoints were the differences in the change in IVUS-derived atheroma volume parameters.

Results: Among 150 patients (mean age 64.2±8.5 years; 27 [18.0%] female) randomised to evolocumab (n=74) or placebo (n=76), 143 underwent follow-up coronary angiography. After 12 weeks of treatment, the adjusted mean change in FFR was 0.00 (95% confidence interval [CI]: -0.02 to 0.02) with evolocumab versus 0.01 (95% CI: -0.01 to 0.03) with placebo (adjusted mean difference: -0.01, 95% CI: -0.03 to 0.01; p=0.6). The adjusted mean change in the maxLCBI4mm was -27.8 (95% CI: -72.2 to 16.6) for evolocumab-treated patients versus -35.6 (95% CI: -82.5 to 11.4) for placebo-treated patients (adjusted mean difference: 7.8, 95% CI: -40.9 to 56.4; p=0.8). No between-group differences in any IVUS-derived parameter were found.

Conclusions: In patients with ACS and relevant non-culprit coronary artery lesions, the addition of evolocumab to HIST for 12 weeks, compared to placebo, did not result in improvement of FFR or maxLCBI4mm. (ClinicalTrials.gov: NCT04141579).

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Conflict of interest statement

M.M. Reda Morsy reports funding from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Education and Training Grants Programme. R.M. Oemrawsingh reports speaker fees from Abbott and Terumo. C. von Birgelen reports institutional research grants from Abbott, Boston Scientific, Biotronik, and Medtronic, outside the current study. A.J.J. IJsselmuiden reports institutional fees from Medtronic, Meril Life Sciences, and Abbott; and consulting fees from Meril Life Sciences, Angiocare, Abbott, Philips, and Translumina. P.C. Smits reports institutional research grants from Abbott and SMT; and consulting or speaker fees from Abbott, MicroPort, SMT, and Terumo; he participates on a data safety monitoring board or advisory board of the LEGACY trial, PROCTOR trial, and on the global coronary advisory board of Abbott; he is a minor shareholder of the European Cardiovascular Research Center. V. Paradies reports institutional grants from Abbott; and personal consulting or speaker fees from Abbott, Boston Scientific, Elixir, and Novo Nordisk; she participates on advisory boards or committees of Boston Scientific, EAPCI Chair Congress Committee, and is an ESC CPC member. C. Camaro reports institutional speaker fees from AstraZeneca and from regional interventional cardiology meetings. P. Damman reports research grants from Abbott, Philips, Pie Medical Imaging, and AstraZeneca; and consulting fees from Philips and Abbott. M.H. van Wely reports consulting fees from Boston Scientific and Abbott. R.A. Byrne reports grants received by the institutions of employment for research or education from Abbott, Biosensors, Boston Scientific, and Translumina, without impact on personal remuneration, and he does not accept personal payments from the medical device or pharmaceutical industry. N. van Royen reports research grants from Biotronik, Abbott, Medtronic, and Philips; and speaker fees from Abbott, RainMed, MicroPort, and Bayer. R.-J.M. van Geuns reports consulting and speaker fees from Abbott and AstraZeneca; and has received institutional research grants from Amgen, InfraRedx, AstraZeneca, and Sanofi. The other authors have no conflicts of interest to declare.

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