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LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry

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Abstract

Purpose

Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting.

Methods

Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included.

Results

The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001).

Conclusion

In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement.

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Data Availability

Not applicable.

References

  1. Mach F, Baigent C, Catapano AL, ESC Scientific Document Group, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):1118–88.

    Article  Google Scholar 

  2. Masana L, Ibarretxe D, Plana N. Maximum low-density lipoprotein cholesterol lowering capacity achievable with drug combinations. When 50 plus 20 equals 60. Rev Esp Cardiol (Engl Ed). 2016;69(3):342–3.

    Article  Google Scholar 

  3. Kotseva K, De Backer G, De Bacquer D, EUROASPIRE Investigators, et al. Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardiol. 2019;26(8):824–35.

    Article  Google Scholar 

  4. Sundbøll J, Larsen AP, Veres K, Adelborg K, Sørensen HT. Cardiovascular event rates and trajectories of LDL-cholesterol levels and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease: a population-based cohort study. Thromb Res. 2019;183:124–30.

    Article  Google Scholar 

  5. Gitt AK, Lautsch D, Ferrieres J, Kastelein J, Drexel H, Horack M, et al. Low-density lipoprotein cholesterol in a global cohort of 57,885 statin-treated patients. Atherosclerosis. 2016;255:200–9.

    Article  CAS  Google Scholar 

  6. Baigent C, Keech A, Kearney PM, Cholesterol Treatment Trialists’ (CTT) Collaborators, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.

    Article  CAS  Google Scholar 

  7. Cholesterol Treatment Trialists’(CTT) Collaboration, Baigent C, Blackwell L, Emberson J, et al. 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(9753):1670–81.

    Article  Google Scholar 

  8. Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–90.

    Article  Google Scholar 

  9. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019;393(10170):407–15.

    Article  Google Scholar 

  10. Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–94.

    Article  CAS  Google Scholar 

  11. Descamps O, Tomassini JE, Lin J, Polis AB, Shah A, Brudi P, et al. Variability of the LDL-C lowering response to ezetimibe and ezetimibe + statin therapy in hypercholesterolemic patients. Atherosclerosis. 2015;240(2):482–9.

    Article  CAS  Google Scholar 

  12. Ridker PM, Mora S, Rose L, JUPITER Trial Study Group. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37(17):1373–9.

    Article  CAS  Google Scholar 

  13. Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG, Black DM, Stein EM, Corella D, et al. Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner. Atherosclerosis. 2001;158(1):183–93.

    Article  CAS  Google Scholar 

  14. Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004;291(23):2821–7.

    Article  CAS  Google Scholar 

  15. Simon JA, Lin F, Hulley SB, Blanche PJ, Waters D, Shiboski S, et al. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) study. Am J Cardiol. 2006;97(6):843–50.

    Article  CAS  Google Scholar 

  16. Bangalore S, Fayyad R, Messerli FH, Laskey R, DeMicco DA, Kastelein JJP, et al. Relation of variability of low-density lipoprotein cholesterol and blood pressure to events in patients with previous myocardial infarction from the IDEAL trial. Am J Cardiol. 2017;119(3):379–87.

    Article  CAS  Google Scholar 

  17. Lin YH, Huang JC, Wu PY, et al. Greater low-density lipoprotein cholesterol variability is associated with increased progression to dialysis in patients with chronic kidney disease stage 3. Oncotarget. 2017;9(3):3242–53.

    Article  Google Scholar 

  18. Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010;35(2):139–51.

    Article  CAS  Google Scholar 

  19. van Himbergen TM, Matthan NR, Resteghini NA, Otokozawa S, Ai M, Stein EA, et al. Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. J Lipid Res. 2009;50(4):730–9.

    Article  Google Scholar 

  20. Karlson BW, Wiklund O, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER. Eur Heart J Cardiovasc Pharmacother. 2016;2(4):212–7.

    Article  CAS  Google Scholar 

  21. Pérez-Calahorra S, Sánchez-Hernández RM, Plana N, Valdivielso P, Civeira F. National dyslipidemia registry of the Spanish Arteriosclerosis Society: current status. Clin Invest Arterioscler. 2017;29(6):248–53.

    Google Scholar 

  22. Nordestgaard BG, Chapman MJ, Humphries SE, European Atherosclerosis Society Consensus Panel, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–90.

    Article  CAS  Google Scholar 

  23. Pedro-Botet J, Rodríguez-Padial L, Brotons C, Esteban-Salán M, García-Lerín A, Pintó X, et al. The ideal lipid report: a need for consensus. Rev Esp Cardiol (Engl Ed). 2018;71(7):512–4.

    Article  Google Scholar 

  24. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81(5):582–7.

    Article  CAS  Google Scholar 

  25. Shaya FT, Sing K, Milam R, Husain F, Del Aguila MA, Patel MY. Lipid-lowering efficacy of ezetimibe in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analyses. Am J Cardiovasc Drugs. 2020;20(3):239–48.

    Article  Google Scholar 

  26. Morrone D, Weintraub WS, Toth PP, Hanson ME, Lowe RS, Lin J, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223(2):251–61.

    Article  CAS  Google Scholar 

  27. Catapano A, Toth PP, Tomassini JE, Tershakovec AM. The efficacy and safety of ezetimibe coadministered with statin therapy in various patient groups. Clin Lipidol. 2013;8(1):13–41.

    Article  CAS  Google Scholar 

  28. Masson M, Lobo M, Maenent D, et al. Response to statins in cardiovascular prevention: hypo-responders’ evaluation. Rev Argent Cardiol. 2014;82:34–41.

    Article  Google Scholar 

  29. Franssen R, Monajemi H, Stroes ES, Kastelein JJ. Obesity and dyslipidemia. Med Clin North Am. 2011;95(5):893–902.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Lipid Units for inclusion of cases in the Dyslipidaemia Registry of the Spanish Arteriosclerosis Society and Miss Christine O’Hara for review of the English version of the manuscript.

Funding

Sanofi provided a research grant to support the trial.

Author information

Authors and Affiliations

  1. Endocrinology and Nutrition Department, Hospital Universitario del Mar, Paseo Marítimo, 25-29, E-08003, Barcelona, Spain

    Elisenda Climent, David Benaiges & Juan Pedro-Botet

  2. Department of Medicine, Universitat Autònoma de Barcelona, Campus Universitari Mar, Dr. Aiguader, 80, E-08003, Barcelona, Spain

    Elisenda Climent, David Benaiges & Juan Pedro-Botet

  3. Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Zaragoza, Spain

    Ana M. Bea

  4. Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Dr. Aiguader, 80, E-08003, Barcelona, Spain

    David Benaiges & Juan Pedro-Botet

  5. Unidad de Lípidos y Riesgo Cardiovascular, Hospital San Pedro, Logroño, Spain

    Ángel Brea-Hernando

  6. Unidad de Lípidos y Riesgo Cardiovascular, Servicio de M. Interna, Hospital Universitario de Bellvitge, Barcelona, Spain

    Xavier Pintó

  7. Unidad de Lípidos y Riesgo Cardiovascular, Hospital San Rafael, A Coruña, Spain

    Manuel Suárez-Tembra

  8. Endocrinology and Nutrition Department, Hospital Universitari Mútua de Terrassa, Terrassa, Spain

    Verónica Perea

  9. Unidad de Medicina Vascular y Metabolismo (UVASMET), Hospital Universitari Sant Joan, IISPV, CIBERDEM, Reus, Tarragona, Spain

    Núria Plana

  10. Biochemistry Service, HSCSP-IIB Sant Pau, Barcelona, Spain

    Francisco Blanco-Vaca

  11. Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Barcelona, Spain

    Francisco Blanco-Vaca

Authors
  1. Elisenda Climent
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  2. Ana M. Bea
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  3. David Benaiges
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  4. Ángel Brea-Hernando
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  5. Xavier Pintó
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  6. Manuel Suárez-Tembra
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  7. Verónica Perea
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  8. Núria Plana
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  9. Francisco Blanco-Vaca
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  10. Juan Pedro-Botet
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Consortia

on behalf of the Dyslipidaemia Registry of the Spanish Atherosclerosis Society

Contributions

The following authors contributed to the study conception and design: AM B, ABH, XP, MST, VP, NP, FBV. Material preparation and data collection were performed by all authors. Data analysis was performed and the first draft of the manuscript was written by EC, DB, and J.P-B, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Juan Pedro-Botet.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval and Consent to Participate

Anonymous clinical data collection in this registry was approved by a central ethics committee (Comité Ético de Investigación Clínica de Aragón, Zaragoza, Spain). Informed consent was obtained from all individual participants included in the study.

Consent for Publication

Not applicable.

Disclaimer

Sanofi had no role in the study design, data collection, analysis, interpretation, report writing, or decision to submit for publication.

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Climent, E., Bea, A.M., Benaiges, D. et al. LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry. Cardiovasc Drugs Ther 36, 301–308 (2022). https://doi.org/10.1007/s10557-020-07137-z

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