Abstract

BackgroundProprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited.MethodsIn this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up.ResultsLDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8–29.2] μm vs 13.2 [7.4–18.6] μm; P = 0.029), greater increases in minimum lumen area (0.20[0.10–0.33] mm2 vs 0.13 [0.12–0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8–24.5] vs. 8.4̊ [2.0–10.5]; P = 0.008).ConclusionsThe addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype.Trial registrationClinicalTrials.gov Identifier: NCT04851769. Registered 2 Mar 2019.

Highlights

  • Low-density lipoprotein (LDL) cholesterol lowering therapy with statins is the cornerstone for effective treatment of coronary artery disease [1, 2]

  • Due to the limited spatial resolution, intravascular ultrasound (IVUS) is unable to evaluate the effects of Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors on fibrous cap thickness (FCT), which has been confirmed as an important indicator of plaque vulnerability [12, 13]

  • It has been well established that LDL cholesterol lowering therapy with statins has favorable effects on reducing coronary atheroma burden and increasing fibrous cap thickness [14, 15], it remains unclear whether the addition of PCSK9 inhibitors could further improve FCT

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Summary

Introduction

Low-density lipoprotein (LDL) cholesterol lowering therapy with statins is the cornerstone for effective treatment of coronary artery disease [1, 2]. Due to the limited spatial resolution, IVUS is unable to evaluate the effects of PCSK9 inhibitors on fibrous cap thickness (FCT), which has been confirmed as an important indicator of plaque vulnerability [12, 13]. It has been well established that LDL cholesterol lowering therapy with statins has favorable effects on reducing coronary atheroma burden and increasing fibrous cap thickness [14, 15], it remains unclear whether the addition of PCSK9 inhibitors could further improve FCT. The aim of this study was to evaluate the effects of PCSK9 inhibitors on fibrous cap thickness by OCT imaging in patients with intermediate coronary lesions. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. Evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited

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