Functional Improvement of Coronary Artery Narrowing by Cholesterol Reduction With a PCSK9 Antibody
Summary
In a large number of patients who experienced an acute coronary syndrome, multiple narrowings of the coronary arteries are identified. Mechanical treatment of the infarct related artery is indisputable, yet mechanical treatment of other bystander lesions in non-infarct related arteries is controversial. Low-density lipoprotein cholesterol can speed up the formation of these coronary artery narrowings, and can increase the risk of a second event. The investigators want to investigate if treating patients with the new cholesterol-lowering drug evolocumab in addition to statin therapy ameliorates blood flow and reduces atherosclerotic plaque size compared with placebo. Improved blood flow and a reduction of plaque size could prevent the need for additional stenting or surgery.
Timeline
- Start
- 2020-11-10
- Primary completion
- 2023-11-09
- Completion
- 2023-11-09
Outcome
Missed primary endpoint
paper 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). PMID 40828313 ↗
paper 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). PMID 40828313 ↗
paper the addition of evolocumab to HIST for 12 weeks, compared to placebo, did not result in improvement of FFR or maxLCBI4mm. PMID 40828313 ↗
Publications
- Los J, Mensink FB, Reda Morsy MM, Nishimiya K, Oemrawsingh RM, IJsselmuiden AJJ, Meuwissen M, Cheng JM, Rai H, Ten Cate TJF, Camaro C, Damman P, van Nunen LX, Dimitriu-Leen AC, van Wely MH, Cetinyurek-Yavuz A, Byrne RA, van Royen N, van Geuns RM. Short-term lesion-level impact of extensive LDL-C reduction with statins and PCSK9 inhibitors: a pre-specified subgroup analysis of the randomized FITTER trial. Clin Res Cardiol. 2026 Mar 23. doi: 10.1007/s00392-026-02869-8. Online ahead of print.
- Mensink FB, Los J, Reda Morsy MM, Oemrawsingh RM, von Birgelen C, Ijsselmuiden AJJ, Meuwissen M, Cheng JM, van Wijk DF, Smits PC, Paradies V, van Wijk DJ, Rai H, Ten Cate TJF, Camaro C, Damman P, van Nunen LX, Dimitriu-Leen AC, van Wely MH, Cetinyurek-Yavuz A, Byrne RA, van Royen N, van Geuns RM. Changes in non-culprit coronary lesions with PCSK9 inhibitors: the randomised, placebo-controlled FITTER trial. EuroIntervention. 2025 Aug 18;21(16):910-920. doi: 10.4244/EIJ-D-24-01065.
- Mensink FB, Los J, Oemrawsingh RM, von Birgelen C, Ijsselmuiden A, Meuwissen M, Cheng JM, van Wijk DF, Smits PC, Paradies V, van der Heijden DJ, Rai H, Ten Cate TJ, Camaro C, Damman P, van Nunen LX, Dimitriu-Leen AC, van Wely MH, Cetinyurek-Yavuz A, Byrne RA, van Royen N, van Geuns RM. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody: Rationale and design of the randomized FITTER trial. Heliyon. 2024 Sep 18;10(19):e38077. doi: 10.1016/j.heliyon.2024.e38077. eCollection 2024 Oct 15.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Evolocumab | Monoclonal antibody | 140 mg | Subcutaneous |