ABSTRACT
Purpose
The lowered LDL-C treatment goal of the 2019 European Society of Cardiology dyslipidemia
guidelines results in a significant increase in the projected need for cost-intensive
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Addition of bempedoic
acid (BA) to established oral lipid-lowering medication (LLM) has the potential to
enable affordable LDL-C goal attainment, particularly in patients with statin intolerance
(SI). The goal of this study was to quantify the target populations for BA and PCSK9
inhibitors as well as the related treatment costs to achieve the LDL-C goal of <55
mg/dL and a ≥50% reduction assuming the addition of BA to LLM.
Methods
This study included 1922 patients with coronary artery disease (CAD) from the contemporary
observational cohort study INTERCATH. A Monte Carlo simulation incorporating an algorithm
adding sequentially a statin, ezetimibe, optionally BA, and a PCSK9 inhibitor was
applied to achieve the LDL-C treatment goal, with consideration of both partial and
total SI. Two scenarios were simulated for both a moderate (2% full and 10% partial)
and a high (12% full) rate of SI: (1) without BA; and (2) with BA.
Findings
Patients’ mean age was 69.3 years, and the median baseline LDL-C level was 86.0 mg/dL.
The need for a PCSK9 inhibitor would be 41.4% for a moderate rate of SI and 46.1%
for a high rate of SI. Addition of BA would: (1) reduce the need for a PCSK9 inhibitor
to 25.3% and 29.4%, thus lowering the annual overall treatment cost incurred through
PCSK9 inhibitor ± BA per 1 million patients with CAD by 13.3% and 10.5%; (2) lower
the cost per prevented event in the entire cohort (–5.0% and –6.3%), although at the
price of fewer prevented events (–8.7% and –4.5%); and (3) reduce the cost per prevented
event (–6.8% for both rates of SI) while preventing more events (7.6% and 6.9%) in
the subpopulation of patients with full SI.
Implications
Use of BA is projected to reduce the need for PCSK9 inhibitors as well as the treatment
cost for add-on LLM. The subpopulation of patients with full SI might profit particularly.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.Eur Heart J. 2020; 41: 111-188
- Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study.Eur Heart J. 2020; 41: 3900-3909
- Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines.Eur J Prev Cardiol. 2021; 28: 59-65
- The need for PCSK9 inhibitors and associated treatment costs according to the 2019 ESC dyslipidaemia guidelines vs. the risk based allocation algorithm of the 2017 ESC consensus statement: a simulation study in a contemporary CAD cohort.Eur J Prev Cardiol. 2021; 28: 47-56
- Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis.Nat Commun. 2016; 7: 13457
- Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia.JAMA Cardiol. 2020; e202314
- Safety and efficacy of bempedoic acid to reduce LDL cholesterol.N Engl J Med. 2019; 380: 1022-1032
CGM Lauer. LAUER-TAXE(R), https://www.cgm.com/lauer-fischer/loesungen_lf/lauer_taxe_lf/lauertaxe_online_4_0/online_en.de.jsp (accessed 6 November 2020).
- Lipid management after first diagnosis of coronary artery disease: contemporary results from an observational cohort study.Clin Ther. 2017; 39 (e2): 2311-2320
- Adherence to Mediterranean diet, high-sensitive C-reactive protein, and severity of coronary artery disease: contemporary data from the INTERCATH cohort.Atherosclerosis. 2018; 275: 256-261
- Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: implications for an anti-inflammatory treatment target population.Eur J Prev Cardiol. 2021; 28: 152-158
- Association of high-sensitivity troponin T and I with the severity of stable coronary artery disease in patients with chronic kidney disease.Atherosclerosis. 2020; 28: 81-87
- Simulation of lipid-lowering therapy intensification in a population with atherosclerotic cardiovascular disease.JAMA Cardiol. 2017; 2: 959-966
- Statin safety and associated adverse events: a scientific statement from the American Heart Association.Arterioscler Thromb Vasc Biol. 2019; 39: e38-e81
- Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet. 2016; 388: 2532-2561
- Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study.Ann Intern Med. 2017; 167: 221-227
- Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; 376: 1713-1722
- Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials.Lancet. 2010; 376: 1670-1681
- Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement fromthe European Atherosclerosis Society Consensus Panel.Eur Heart J. 2017; 38: 2459-2472
- Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy.Eur J Prev Cardiol. 2020; 27: 593-603
- Bempedoic acid for high-risk patients with CVD as adjunct lipid-lowering therapy: a cost-effectiveness analysis.J Clin Lipidol. 2020; 14: 772-783
- Rationale and design of the CLEAR-outcomes trial: evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance.Am Heart J. 2021; 235: 104-112
- Mendelian randomization study of ACLY and cardiovascular disease.N Engl J Med. 2019; 380: 1033-1042
- Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.JAMA. 2016; 316: 1289-1297
- Impact of PCSK9 inhibitors on the quality of life of patients at high cardiovascular risk.Eur J Prev Cardiol. 2020; 27: 556-558
- Two Phase 3 trials of inclisiran in patients with elevated LDL cholesterol.N Engl J Med. 2020; 382: 1507-1519
- EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study.Eur J Prev Cardiol. 28 August 2020; (Epub ahead of print)
Article info
Publication history
Published online: August 27, 2021
Accepted:
July 26,
2021
Identification
Copyright
© 2021 Elsevier Inc.
