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Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 European Society of Cardiology Congress

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Abstract

Purpose of Review

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 European Society of Cardiology (ESC) congress.

Recent Findings

The NATURE-PARADOX was a naturally randomized trial that used genetic data from the UK Biobank registry to create “cumulative exposure to low-density lipoprotein-cholesterol (LDL-C)” biomarker and evaluate its association with major CV events regardless of plasma LDL-C levels or age. Safety and efficacy data of inclisiran, a PCSK9-interfering mRNA (PCSK9i) administered subcutaneously twice annually, were presented. Data on two new PCSK9is were presented, recaticimab, an oral drug, and lerodalcibep, a subcutaneous drug with a slightly different architecture than currently available PSCK9is. A phase 1 trial on muvalaplin, an oral lipoprotein (a) inhibitor, was presented. An atherosclerotic CV disease (ASCVD) risk prediction algorithm for the Asian population using SCORE2 data was presented. Long-term follow-up of patients enrolled in the CLEAR outcomes trial showed sustained and more significant ASCVD risk reduction with bempedoic acid in high-risk patients.

Summary

The late-breaking clinical science at the 2023 congress of the ESC extends the known safety and efficacy data of a PCSK9i with the introduction of new drugs in this class. Using cumulative exposure to LDL-C rather than a single value will help clinicians tailor the LDL-C reduction strategy to individual risk and is an important step towards personalized medicine.

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Abbreviations

ADA:

Anti-drug antibodies

apo:

Apolipoprotein

ARR:

Absolute risk reduction

ASCVD:

Atherosclerotic cardiovascular disease

BMI:

Body mass index

CAD:

Coronary artery disease

CI:

Confidence interval

CKD:

Chronic kidney disease

CV:

Cardiovascular

DM:

Diabetes mellitus

ESC:

European Society of Cardiology

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

HeFH:

Heterozygous familial hypercholesterolemia

HIS:

High-intensity statin

HR:

Hazard ratio

Hrs:

Hours

HTN:

Hypertension

LCHF:

Low carbohydrate-high fat

LDL-C:

Low-density lipoprotein cholesterol

MACE:

Major adverse cardiovascular events

MAD:

Multiple ascending doses

MCE:

Major coronary events

MI:

Myocardial infarction

NNH:

Number needed to harm

NNI:

Number needed to invite

oxPL:

Oxidized phospholipids

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PET:

Positron emission tomography

RCT:

Randomized control trial

SAD:

Single ascending dose

SBP:

Systolic blood pressure

TG:

Triglycerides

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gupta K, Balachandran I, Foy J, et al. Highlights of cardiovascular disease prevention studies presented at the 2023 American College of Cardiology Conference. Curr Atheroscler Rep. 2023;25(6):309–21. https://doi.org/10.1007/s11883-023-01103-4.

    Article  CAS  PubMed  Google Scholar 

  2. Gupta K, Hirsch JR, Kalsi J, Patel V, Gad MM, Virani SS. Highlights of cardiovascular disease prevention studies presented at the 2022 American Heart Association Scientific Sessions. Curr Atheroscler Rep. 2023;25(1):31–41. https://doi.org/10.1007/s11883-022-01079-7.

    Article  CAS  PubMed  Google Scholar 

  3. • Shapiro MD, Bhatt DL. “Cholesterol-years” for ASCVD risk prediction and treatment∗. J Am Coll Cardiol. 2020;76(13):1517–20. https://doi.org/10.1016/j.jacc.2020.08.004. Provides context to the studies discussed here.

    Article  PubMed  Google Scholar 

  4. Nayor M, Brown KJ, Vasan RS. The molecular basis of predicting atherosclerotic cardiovascular disease risk. Circ Res. 2021;128(2):287–303. https://doi.org/10.1161/CIRCRESAHA.120.315890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. • Virani SS, Ballantyne CM. Low-density lipoprotein cholesterol. Circulation. 2018;138(21):2326–9. https://doi.org/10.1161/CIRCULATIONAHA.118.034922. Provides context to the studies discussed here.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kitkungvan D, Johnson NP, Kirkeeide R, et al. Design and rationale of the randomized trial of comprehensive lifestyle modification, optimal pharmacological treatment and utilizing PET imaging for quantifying and managing stable coronary artery disease (the CENTURY study). Am Heart J. 2021;237:135–46. https://doi.org/10.1016/j.ahj.2021.03.012.

    Article  CAS  PubMed  Google Scholar 

  7. • Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–46. https://doi.org/10.1093/eurheartj/ehac361. Laid the groundwork and provides context to the studies discussed here.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. • Nicholls SJ, Nissen SE, Fleming C, Urva S, Suico J, Berg PH, Linnebjerg H, Ruotolo G, Turner PK, Michael LF. Muvalaplin, an oral small molecule inhibitor of lipoprotein(a) formation: a randomized clinical trial. JAMA. 2023;330(11):1042–53. https://doi.org/10.1001/jama.2023.16503. Original article for the study discussed that was simultaneously published.

  9. Koren MJ, Moriarty PM, Baum SJ, et al. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med. 2022;28(1):96–103. https://doi.org/10.1038/s41591-021-01634-w.

    Article  CAS  PubMed  Google Scholar 

  10. O’Donoghue ML, G López JA, Knusel B, et al. Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE). Am Heart J. 2022;251:61–9. https://doi.org/10.1016/j.ahj.2022.05.004. Laid the groundwork and provides context to the studies discussed here.

    Article  CAS  PubMed  Google Scholar 

  11. Kronenberg F, Mora S, Stroes ESG, et al. Frequent questions and responses on the 2022 lipoprotein(a) consensus statement of the European Atherosclerosis Society. Atherosclerosis. 2023;374:107–20. https://doi.org/10.1016/j.atherosclerosis.2023.04.012.

    Article  CAS  PubMed  Google Scholar 

  12. Virani SS, Koschinsky ML, Maher L, et al. Global think tank on the clinical considerations and management of lipoprotein(a): the top questions and answers regarding what clinicians need to know. Prog Cardiovasc Dis. 2022;73:32–40. https://doi.org/10.1016/j.pcad.2022.01.002.

    Article  PubMed  Google Scholar 

  13. O’Donoghue ML, Rosenson RS, Gencer B, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med. 2022;387(20):1855–64. https://doi.org/10.1056/NEJMoa2211023.

    Article  PubMed  Google Scholar 

  14. Lindholt JS, Søgaard R, Rasmussen LM, et al. Five-year outcomes of the danish cardiovascular screening (DANCAVAS) trial. N Engl J Med. 2022;387(15):1385–94. https://doi.org/10.1056/NEJMoa2208681.

    Article  PubMed  Google Scholar 

  15. •• Ray KK, Wright RS, Kallend D, et al. Two Phase 3 Trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507–19. https://doi.org/10.1056/NEJMoa1912387. Laid the groundwork and provides context to the studies discussed here.

    Article  CAS  PubMed  Google Scholar 

  16. •• Ray KK, Troquay RPT, Visseren FLJ, et al. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023;11(2):109–19. https://doi.org/10.1016/S2213-8587(22)00353-9. Laid the groundwork and provides context to the studies discussed here.

    Article  CAS  PubMed  Google Scholar 

  17. Ray KK, Kallend D, Leiter LA, et al. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J. 2022;43(48):5047–57. https://doi.org/10.1093/eurheartj/ehac615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388(15):1353–64. https://doi.org/10.1056/NEJMoa2215024.

    Article  PubMed  Google Scholar 

  19. Andersen PK, Gill RD. Cox’s regression model for counting processes: a large sample study. Ann Stat. 1982;10(4):1100–20. https://doi.org/10.1214/aos/1176345976.

    Article  Google Scholar 

  20. SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021;42(25):2439–54. https://doi.org/10.1093/eurheartj/ehab309.

    Article  CAS  Google Scholar 

  21. Xu M, Zhu X, Wu J, et al. PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study. BMC Med. 2022;20(1):13. https://doi.org/10.1186/s12916-021-02208-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol. 2020;75(20):2553–66. https://doi.org/10.1016/j.jacc.2020.03.057.

    Article  CAS  PubMed  Google Scholar 

  23. Stein EA, Turner T, Kereiakes DJ, Butcher B, Mangu P, Zhou R. Abstract 17222: Safety, tolerability and LDL-C reduction with LIB003 a novel anti-PCSK9 recombinant fusion protein: Results of open-label extension phase 2B study. Circulation. 2019;140(Suppl_1):A17222–A17222. https://doi.org/10.1161/circ.140.suppl_1.17222.

    Article  Google Scholar 

  24. •• Raal F, Fourie N, Scott R, Blom D, De Vries Basson M, Kayikcioglu M, Caldwell K, Kallend D, Stein E; LIBerate-HeFH Investigators. Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial. Eur Heart J. 2023;44(40):4272–80. https://doi.org/10.1093/eurheartj/ehad596. Original article for the study discussed that was simultaneously published.

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Funding

Dr. Virani is supported by the Department of Veterans Affairs, NIH, Tahir, and Jooma Family Foundation. Dr. Slipczuk has received institutional grants from Amgen and Philips.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Diseases, Henry Ford Hospital, Detroit, MI, USA

    Kartik Gupta

  2. Division of Cardiovascular Diseases, The Texas Heart Institute, Houston, TX, USA

    Colin Hinkamp, Chelsea Meloche & Salim S. Virani

  3. Department of Medicine, Henry Ford Hospital, Detroit, MI, USA

    Tyler Andrews

  4. Section of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Abdul Mannan Khan Minhas, Elizabeth Vaughan & Salim S. Virani

  5. Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA

    Leandro Slipczuk

  6. Department of Internal Medicine, Medical Branch, University of Texas, Galveston, TX, USA

    Elizabeth Vaughan

  7. Section of Cardiology, Department of Medicine, The Aga Khan University, Karachi, Pakistan

    Fatima Zohra Habib, Sana Sheikh & Salim S. Virani

  8. Rudd Heart & Lung Center, University of Louisville School of Medicine, Louisville, KY, USA

    Dinesh Kalra

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  1. Kartik Gupta
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Contributions

KG, CH, TA, CM, and AMKM reviewed the literature independently and wrote the first draft of the manuscript. LS, EV, FZH, SS, DK reviewed the content for accuracy and clinical implications. KG and SSV concevied the idea. SSV provided overall supervision.

Corresponding author

Correspondence to Salim S. Virani.

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Competing Interests

Dr. Virani is a Section Editor for the Springer journals Current Atherosclerosis Reports and Current Cardiology Reports. Dr. Slipczuk has received consulting honorarium from Amgen and Philips, participated in the advisory board for Bristol-Myers-Squib, and serves as site PI for V-INITIATE and Ocean(a) trials. The other authors declare that they have no conflict of interest.

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Gupta, K., Hinkamp, C., Andrews, T. et al. Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 European Society of Cardiology Congress. Curr Atheroscler Rep 25, 965–978 (2023). https://doi.org/10.1007/s11883-023-01164-5

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