Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De‐novo heart transplant recipients: Design of the randomized controlled EVOLVD trial

Broch, Kaspar; Gude, Einar; Karason, Kristjan; Dellgren, Göran; Rådegran, Göran; Gjesdal, Grunde; Gustafsson, Finn; Eiskjær, Hans; Lommi, Jyri; Pentikäinen, Markku O.; Lemström, Karl; Andreassen, Arne K.; Gullestad, Lars

doi:10.1111/ctr.13984

Cited by 22 publications

(10 citation statements)

References 22 publications

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“…Unfortunately, none of the current patients were treated with PCSK-inhibitors, so evidence cannot be shown on their effectiveness. However, evidence in heart transplant recipients and data regarding their potential influence on CAV is still limited, and further results are expected to be announced in the coming years [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation

et al. 2022

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Background Cardiac allograft vasculopathy (CAV) is a major prognosis limiting factor in heart transplantation (HTx). Disease development and progression are influenced by multiple determinants, but the role of remnant cholesterol (RC) in CAV has not yet been investigated. Therefore, the present study aimed to assess the prevalence of CAV in a very long-term follow-up after orthotopic HTx and to examine the role of RC in residual inflammation despite secondary prevention. Methods Herein, is a retrospective analysis of patient data collected at the last follow-up visit in an outpatient setting. Additionally, RC levels were calculated based upon cholesterol profile. Results The study population consisted of 184 patients with a mean follow-up of 15.0 ± 6.8 years. More than 40% of the overall cohort had CAV at last follow-up. The mean RC was 27.1 ± 14.7 mg/dL. Patients with CAV had significantly elevated RC despite intensified statin treatment (p = 0.018). A positive correlation was observed between RC and interleukin-6 as a marker of residual inflammation. Elevated RC and prolonged follow-up emerged as significant factors related to CAV in a multivariate analysis (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5–5.5, p = 0.001 and OR 3.3, 95% CI 1.4–7.7, p = 0.006, respectively), whereas mycophenolate mofetil was inversely associated with CAV (OR 0.4, 95% CI 0.2–0.9, p = 0.034). Conclusions Remnant cholesterol has proinflammatory properties and is associated with CAV development in HTx. Thus, RC should be concerned as an additional tool for risk assessment.

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Section: Discussionmentioning

confidence: 99%

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation

et al. 2022

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“…PCSK9 may serve as a potential treatment target in HTx patients and at present, there are ongoing randomized controlled studies with PCSK9 inhibition to prevent CAV development in de novo HTx patients 24 …”

Section: Discussionmentioning

confidence: 99%

Micro‐ and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients—An exploratory study

Bjerre

Clemmensen

Poulsen

et al. 2020

Clinical Transplantation

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Background Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro‐ and macrovascular CAV and major adverse cardiac events in HTx patients. Methods We evaluated 91 cardiovascular disease‐related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro‐ and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15O‐H2O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death. Results We found consistent differences in two proteins involved in cholesterol homeostasis: significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p < .05) and significantly decreased paraoxonase 3 (PON3) (p < .05). N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was significantly increased in patients with microvascular CAV (p < .05) and borderline significantly increased in patients experiencing major adverse cardiac events (p = .10) and patients with macrovascular CAV (p = .05). Conclusions We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT‐proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.

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“…In regard to this action on coronary disease, in the next years, the EVOLVD trial will try to prove the reduction in CAV incidence in heart transplant patients treated with evolocumab [ 104 ].…”

Section: Pcsk9 Inhibitors Use In Transplant Patientsmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients

Cuomo

Cioffi

Lorenzo

et al. 2022

JCM

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Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits.

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Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De‐novo heart transplant recipients: Design of the randomized controlled EVOLVD trial

Cited by 22 publications

References 22 publications

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation

Micro‐ and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients—An exploratory study

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients

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