Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients
Graphical abstract
Introduction
Dyslipidaemias are a cardinal cardiovascular (CV) risk factor and their therapeutic targeting is of paramount importance for the prevention of events [1]. Pharmacological therapeutic strategies are based mostly on statins and ezetimibe that have been shown to effectively reduce CV risk [[2], [3], [4]].
However, the therapeutic potential of statins and ezetimibe is not unlimited. A considerable percentage of patients do not reach therapeutic targets despite optimal intensification of regimen. This is more prominent in familial hypercholesterolaemia patients (FH) who have excessively high LDL levels [5,6]. Further, side effects, with myalgia being the most common one in the case of statins [7], prohibit patients from maximizing the dose or even taking any hypolipidaemic agent whatsoever.
Proprotein convertase subtilisin–kexin type 9 (PCSK9) promotes degradation of LDL receptors, thereby diminishing the clearance of LDL from the circulation. [8,9] PCSK9 inhibitors (PCSK-9i) are monoclonal antibodies which effectively impede the binding of the proprotein with LDL receptors (LDLR), and thus reduce low-density cholesterol (LDLc) levels by up to 60% on top of statins and ezetimibe [10,11]. Importantly, major clinical trials, such as the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) [12] and ODYSSEY (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) [13] have shown significant reduction of CV events in high-risk patients.
On the other hand, the cost of PCSK9 inhibitors poses considerations for reimbursement and, accordingly, a realistic estimation of the figures of patients eligible for this treatment is of paramount importance for the planning of national health systems regarding their targeted integration in clinical practice [14]. Currently, there is a considerable worldwide variation of criteria for PCSK9i reimbursement. Further, in light of recent data, treatment goals are continuously evolving towards stricter values [[15], [16], [17]]. The aim of this single-institute cross sectional observational study was to develop a prediction model that is based on individual patient characteristics and would be adjustable according to various guidelines/national criteria and clinical scenarios. Based on a 2000 patient cohort consisting of acute coronary syndrome patients, chronic coronary artery disease patients and specialized lipid outpatients’ clinic, we provide real-world numbers for eligibility for PCSK9i treatment according to the 2019 and 2016 ESC/EAS dyslipidaemia guidelines, the 2017 American College of Cardiology Expert Consensus, and according to LDLc goals of <100 mg/dl and <130 mg/dl (for very high-risk and high-risk patients, respectively) that are currently applicable to various national health systems.
Section snippets
Patient population
We enrolled 2000 patients from August 1, 2018 to August 31, 2019. Inclusion criteria included age ≥18 years and provision of informed consent, while patients were excluded if they had communication problems. We categorised patients into three groups: (i) inpatients diagnosed with acute coronary syndrome (ACS) enrolled in a consecutive manner, (ii) inpatients diagnosed with chronic coronary artery disease (cCAD) enrolled in a random manner through the lottery method at a pace of approximately 20
Baseline characteristics
Baseline characteristics with sub-analysis for each group are shown in Table 1. Age of the total population was 65 ± 13.65 years and 71% were males. A quarter (25.3%) of the total population originated from the OLC and the remaining three quarters (74.6%) from the hospital's inpatient population. The latter were further classified as 54% with cCAD and 20% with ACS. Hypertension was present in 65% of the total population, diabetes in 30%, smoking in 31%, premature familial CAD in 11%, early
Discussion
We present for the first time a realistic estimation of PCSK9i eligibility based on data obtained on a prospective manner in 2000 patients. Eligibility was calculated utilizing a custom-made predictive model that is adjustable according to different thresholds and clinical scenaria. Eligibility for PCSK9i administration varies from 2.15% to 18.85% according to National, ACC and ESC/EAS Guidelines. Eligibility also varies according to the clinical status of the patient, i.e. ACS, chronic CAD and
Financial support
This work was supported by Amgen Hellas LTD, Greece (Funding ID 3PartySpon-148305). The funding company had no involvement in the collection, analysis and interpretation of the data, in the writing of the report, or with the preparation, review, approval and submission of the manuscript.
Author contributions
Dr Vlachopoulos contributed to conception and design of the study, acquisition, analysis and interpretation of data, critically revised the manuscript and gave final approval. Dr Dima has contributed to design, acquisition, analysis and interpretation of data, critically revised the manuscript and gave final approval. Dr Soulis and Dr Terentes-Printzios contributed to design and analysis of data, drafted the manuscript and gave final approval. Dr Skoumas, Dr Aznaouridis, Dr Solomou, Dr Richter
CRediT authorship contribution statement
Charalambos Vlachopoulos: Conceptualization, Methodology, Validation, Writing - review & editing, Supervision, Project administration, Funding acquisition. Ioanna Dima: Investigation, Formal analysis, Data curation, Writing - original draft, Visualization. Dimitrios Soulis: Methodology, Software, Resources, Data curation. Dimitrios Terentes-Printzios: Methodology, Data curation. Ioannis Skoumas: Resources, Validation. Konstantinos Aznaouridis: Validation, Resources. Eirini Solomou: Resources,
Declaration of competing interest
Dr Vlachopoulos and Dr Richter have received research grants and honoraria from Amgen, Elpen, Mylan, MSD, Sanofi and Servier outside the submitted work. Dr Skoumas has received research grants and honoraria from Amgen, Sanofi, MSD, and Elpen and Dr Tousoulis has received research grants and honoraria from Amgen, Pfizer, MSD, Boehringer Ingelheim, and Sanofi outside the submitted work. Dr Dima and Dr Soulis have received a research grant for the submitted work. The other the authors have nothing
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2021, International Journal of CardiologyCitation Excerpt :Furthermore, a study of 2000 patients with hyperlipidemia reported that 18.9% were eligible for PCSK9i treatment based on the latest ESC/EAS guidelines [25]. In a small subgroup of patients (n = 136) which were classified as probable/definite heterozygous FH patients, 39% (n = 53) were eligible for PCSK9i administration [25]. A major barrier for the reimbursement of PCKS9i treatment by healthcare systems is the high economic cost for the expected health benefit [26].
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