Adding Alirocumab to Rosuvastatin Helps Reduce the Vulnerability of Thin-Cap Fibroatheroma

Sugizaki, Yoichiro; Otake, Hiromasa; Kawamori, Hiroyuki; Toba, Takayoshi; Nagano, Yuichiro; Tsukiyama, Yoshiro; Yanaka, Kenichi; Yamamoto, Hiroyuki; Nagasawa, Akira; Onishi, Hideaki; Takeshige, Ryo; Nakano, Shinsuke; Matsuoka, Yoichiro; Tanimura, Kosuke; Takahashi, Yu; Fukuyama, Yoshikazu; Shinke, Toshiro; Ishida, Tatsuro; Hirata, Ken-ichi

doi:10.1016/j.jcmg.2020.01.021

Cited by 28 publications

(16 citation statements)

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“…A recent retrospective, observational OCT study revealed that evolocumab provided a greater increase in FCT in patients with recent acute coronary syndrome than statin monotherapy [ 25 ]. To date, there is only one randomized study evaluating the effects of PCSK9 inhibitors on plaque morphology by OCT – the ALTAIR study [ 26 ]. It enrolled 24 patients randomized to either alirocumab or statins (rosuvastatin 10 mg/d).…”

Section: Discussionmentioning

confidence: 99%

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

et al. 2021

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Background 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. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited. Methods In 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. Results LDL 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). Conclusions The 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 registration ClinicalTrials.gov Identifier: NCT04851769. Registered 2 Mar 2019.

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Section: Discussionmentioning

confidence: 99%

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

et al. 2021

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“…Two single-center trials used optical coherence tomography to investigate the effects of PCSK9-antibodies vascular structure: Firstly, a retrospective study reported that treatment with evolocumab for 12 weeks increased fibrous-cap thickness and reduced the lipid-rich plaque proportion in 18 patients (intervention group) with acute coronary syndromes [ 9 ]. Secondly, a prospective randomized trial reported that treatment with alirocumab for 36 weeks also increased fibrous cap thickness and reduced the lipid content of plaques in 12 patients (intervention group) with coronary artery disease [ 10 ]. Most recently, the HUYGENS phase 3 trial investigated the effects of 52 weeks evolocumab treatment on fibrous cap thickness by optical coherence tomography.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies reduces plasma LDL-cholesterol by as much as 60% [ 4 , 5 , 6 ]. In addition, treatment with PCSK9-antibodies has been demonstrated to be associated with plaque regression and higher plaque stability measured by intravascular ultrasound and optical coherence tomography [ 7 , 8 , 9 , 10 ]. However, intravascular ultrasound and optical coherence tomography both carry the risk of invasive procedures such as hematoma after an arterial puncture, infection, allergy against contrast media, or catheter-induced endothelial damage.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

et al. 2022

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Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

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“…Therefore, intensive LDL-C lowering with alirocumab has a favourable effect on plaque stabilization. 24 More recently, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy in patients with acute MI resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. 25 Whether earlier initiation of treatment (i.e., prior to hospital discharge after ACS) would magnify an early treatment benefit is a hypothesis worthy of testing prospectively.…”

Section: A Previous Analysis Of the Further Cardiovascular Outcomes R...mentioning

confidence: 99%

Alirocumab and Cardiovascular Outcomes in Patients With Previous Myocardial Infarction: Prespecified Subanalysis From ODYSSEY OUTCOMES

Chiang¹,

Schwartz²,

Elbez³

et al. 2022

Canadian Journal of Cardiology

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Adding Alirocumab to Rosuvastatin Helps Reduce the Vulnerability of Thin-Cap Fibroatheroma

Cited by 28 publications

References 1 publication

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

Alirocumab and Cardiovascular Outcomes in Patients With Previous Myocardial Infarction: Prespecified Subanalysis From ODYSSEY OUTCOMES

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