Skip to main content

Advertisement

SpringerLink
Log in

Statin withdrawal and health-related quality of life in a primary cardiovascular prevention cohort

  • Published:
Quality of Life Research Aims and scope Submit manuscript

Abstract

Purpose

While some work has been done on Health-Related Quality of Life (HRQoL) in statin users, none has focused specifically on statin-associated muscle symptoms (SAMS) sufferers. The objective was to assess self-reported HRQoL, before and after statin withdrawal, in patients reporting SAMS. We hypothesized that the presence of SAMS associated with decreased self-reported physical and mental well-being.

Methods

Patients (50 men/28 women [M/W], aged 49 ± 9 years [Mean ± SD]) in primary cardiovascular prevention were recruited into three cohorts: statin users with (SAMS, 29 M/18W) or without symptoms (No SAMS, 10 M/5W) and controls (11 M/5W). The Short Form 36 Health Survey (SF-36) was used to assess HRQoL. All variables were measured before and after 2 months of statin withdrawal, and repeated measures analyses were used to verify withdrawal and group effects as well as their interaction.

Results

SF-36 physical and mental component scores (respectively, PCS and MCS) were lower in the SAMS group compared with other groups (both p < 0.01). Statin withdrawal led to an increase in LDL cholesterol for statin users (+69.0%, p < 0.01) and an improvement in well-being in the SAMS group, other groups showing no change. A time x category interaction (p = 0.02) was seen for PCS and post hoc analyses showed that statin withdrawal improved PCS and MCS (respectively, +12.5% [ES 0.77] and +5.1% [ES 0.27], both p < 0.05) in the SAMS group.

Conclusion

Patients self-reporting SAMS showed improved HRQoL following drug withdrawal, but this was mirrored by a rise in LDL cholesterol. These findings should be considered by clinicians in the evaluation and follow-up of treatment with statins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig.3

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author [DRJ].

References

  1. Cohen, J. D., Brinton, E. A., Ito, M. K., & Jacobson, T. A. (2012). Understanding Statin use in America and gaps in patient Education (USAGE): an internet-based survey of 10138 current and former statin users. Journal of Clinical Lipidology, 6(3), 208–215. https://doi.org/10.1016/j.jacl.2012.03.003

    Article  PubMed  Google Scholar 

  2. Sivashanmugarajah, A., Fulcher, J., Sullivan, D., Elam, M., Jenkins, A., & Keech, A. (2019). Suggested clinical approach for the diagnosis and management of ‘statin intolerance’ with an emphasis on muscle-related side-effects. Internal Medicine Journal, 49(9), 1081–1091. https://doi.org/10.1111/imj.14429

    Article  PubMed  Google Scholar 

  3. Ridker, P. M., Danielson, E., Fonseca, F. A., Genest, J., Gotto, A. M., Jr., Kastelein, J. J., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., Nordestgaard, B. G., Shepherd, J., Willerson, J. T., & Glynn, R. J. (2008). Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New England Journal of Medicine, 359(21), 2195–2207. https://doi.org/10.1056/NEJMoa0807646

    Article  CAS  PubMed  Google Scholar 

  4. Thompson, P. D., Panza, G., Zaleski, A., & Taylor, B. (2016). Statin-associated side effects. Journal of the American College of Cardiology, 67(20), 2395–2410. https://doi.org/10.1016/j.jacc.2016.02.071

    Article  CAS  PubMed  Google Scholar 

  5. Wagstaff, L. R., Mitton, M. W., Arvik, B. M., & Doraiswamy, P. M. (2003). Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 23(7), 871–880. https://doi.org/10.1592/phco.23.7.871.32720

    Article  Google Scholar 

  6. Bruckert, E., Hayem, G., Dejager, S., Yau, C., & Begaud, B. (2005). Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients–the PRIMO study. Cardiovascular Drugs and Therapy, 19(6), 403–414. https://doi.org/10.1007/s10557-005-5686-z

    Article  CAS  PubMed  Google Scholar 

  7. Selva-O’Callaghan, A., Alvarado-Cardenas, M., Pinal-Fernandez, I., Trallero-Araguas, E., Milisenda, J. C., Martinez, M. A., Marin, A., Labrador-Horrillo, M., Juarez, C., & Grau-Junyent, J. M. (2018). Statin-induced myalgia and myositis: An update on pathogenesis and clinical recommendations. Expert Review of Clinical Immunology, 14(3), 215–224. https://doi.org/10.1080/1744666X.2018.1440206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stroes, E. S., Thompson, P. D., Corsini, A., Vladutiu, G. D., Raal, F. J., Ray, K. K., Roden, M., Stein, E., Tokgozoglu, L., Nordestgaard, B. G., Bruckert, E., De Backer, G., Krauss, R. M., Laufs, U., Santos, R. D., Hegele, R. A., Hovingh, G. K., Leiter, L. A., Mach, F., … P European Atherosclerosis Society Consensus. (2015). Statin-associated muscle symptoms: impact on statin therapy-European atherosclerosis Society consensus panel statement on assessment aetiology and management. European Heart Journal, 36(17), 1012–1022. https://doi.org/10.1093/eurheartj/ehv043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bouitbir, J., Sanvee, G. M., Panajatovic, M. V., Singh, F., & Krahenbuhl, S. (2020). Mechanisms of statin-associated skeletal muscle-associated symptoms. Pharmacological Research, 154, 104201. https://doi.org/10.1016/j.phrs.2019.03.010

    Article  CAS  PubMed  Google Scholar 

  10. Taylor, B. A., & Thompson, P. D. (2018). Statin-associated muscle disease: Advances in diagnosis and management. Neurotherapeutics, 15(4), 1006–1017. https://doi.org/10.1007/s13311-018-0670-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Turner, R. M., & Pirmohamed, M. (2019). Statin-related myotoxicity: A comprehensive review of pharmacokinetic, pharmacogenomic and muscle components. Journal of Clinical Medicine, 9, 1. https://doi.org/10.3390/jcm9010022

    Article  CAS  Google Scholar 

  12. Blacher, J., Bruckert, E., Farnier, M., Ferrieres, J., Henry, P., Krempf, M., & Mourad, J. J. (2019). Myalgia and statins: Separating the true from the false. La Presse Médicale, 48(10), 1059–1064. https://doi.org/10.1016/j.lpm.2019.07.034. (Myalgies et statines : demeler le vrai du faux.).

    Article  PubMed  Google Scholar 

  13. Hauser, W., Hansen, E., & Enck, P. (2012). Nocebo phenomena in medicine: their relevance in everyday clinical practice. Deutsches Ärzteblatt international, 109(26), 459–465. https://doi.org/10.3238/arztebl.2012.0459

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pedro-Botet, J., Climent, E., & Benaiges, D. (2019). Muscle and statins from toxicity to the nocebo effect. Expert Opinion on Drug Safety, 18(7), 573–579. https://doi.org/10.1080/14740338.2019.1615053

    Article  PubMed  Google Scholar 

  15. Robinson, J. G. (2019). New insights into managing symptoms during statin therapy. Progress in Cardiovascular Diseases, 62(5), 390–394. https://doi.org/10.1016/j.pcad.2019.10.005

    Article  PubMed  Google Scholar 

  16. Alonso, R., Cuevas, A., & Cafferata, A. (2019). Diagnosis and management of statin intolerance. Journal of Atherosclerosis and Thrombosis, 26(3), 207–215. https://doi.org/10.5551/jat.RV17030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rosenson, R. S., Miller, K., Bayliss, M., Sanchez, R. J., Baccara-Dinet, M. T., Chibedi-De-Roche, D., Taylor, B., Khan, I., Manvelian, G., White, M., & Jacobson, T. A. (2017). The statin-associated muscle symptom clinical index (SAMS-CI): Revision for clinical use, content validation, and inter-rater reliability. Cardiovascular Drugs and Therapy, 31(2), 179–186. https://doi.org/10.1007/s10557-017-6723-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carlsson, C. M., Papcke-Benson, K., Carnes, M., McBride, P. E., & Stein, J. H. (2002). Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Drugs & aging, 19(10), 793–805. https://doi.org/10.2165/00002512-200219100-00008

    Article  CAS  Google Scholar 

  19. Hyttinen, L., Kekalainen, P., Vuorio, A. F., Sintonen, H., & Strandberg, T. E. (2008). Health-related quality of life in elderly patients with familial hypercholesterolemia. International Journal Of Technology Assessment In Health Care, 24(2), 228–234. https://doi.org/10.1017/S0266462308080318

    Article  PubMed  Google Scholar 

  20. Mohler, E. R., 3rd., Hiatt, W. R., & Creager, M. A. (2003). Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation, 108(12), 1481–1486. https://doi.org/10.1161/01.CIR.0000090686.57897.F5

    Article  CAS  PubMed  Google Scholar 

  21. Solberg, O. G., Stavem, K., Ragnarsson, A., Beitnes, J. O., Skårdal, R., Seljeflot, I., Ueland, T., Aukrust, P., Gullestad, L., & Aaberge, L. (2019). Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study. Catheterization and Cardiovascular Interventions, 94(5), 660–668. https://doi.org/10.1002/ccd.28157

    Article  PubMed  Google Scholar 

  22. Strandberg, T. E., Urtamo, A., Kahara, J., Strandberg, A. Y., Pitkala, K. H., & Kautiainen, H. (2018). Statin treatment is associated with a neutral effect on health-related quality of life among community-dwelling octogenarian men: The helsinki businessmen study. The Journals of Gerontology: Series A, 73(10), 1418–1423. https://doi.org/10.1093/gerona/gly073

    Article  Google Scholar 

  23. van Boheemen, L., Tett, S. E., Sohl, E., Hugtenburg, J. G., van Schoor, N. M., & Peeters, G. M. (2016). Associations between statin use and physical function in older adults from the Netherlands and Australia: longitudinal aging study Amsterdam and Australian longitudinal study on women’s health. Drugs Aging., 33(6), 437–445. https://doi.org/10.1007/s40266-016-0370-5

    Article  CAS  PubMed  Google Scholar 

  24. Downs, J. R., Oster, G., & Santanello, N. C. (1993). HMG CoA reductase inhibitors and quality of life. JAMA, 269(24), 3107–3108. https://doi.org/10.1001/jama.1993.03500240051020

    Article  CAS  PubMed  Google Scholar 

  25. Cham, S., Evans, M. A., Denenberg, J. O., & Golomb, B. A. (2010). Statin-associated muscle-related adverse effects: A case series of 354 patients. Pharmacotherapy, 30(6), 541–553. https://doi.org/10.1592/phco.30.6.541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Evans, M. A., & Golomb, B. A. (2009). Statin-associated adverse cognitive effects: Survey results from 171 patients. Pharmacotherapy, 29(7), 541–553. https://doi.org/10.1592/phco.29.7.800

    Article  Google Scholar 

  27. Bhardwaj, S., Selvarajah, S., & Schneider, E. B. (2013). Muscular effects of statins in the elderly female: A review. Clinical Interventions in Aging, 8, 47–59. https://doi.org/10.2147/CIA.S29686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Phillips, P. S., Haas, R. H., Bannykh, S., Hathaway, S., Gray, N. L., Kimura, B. J., Vladutiu, G. D., & England, J. D. F. (2002). Statin-associated myopathy with normal creatine kinase levels. Annals of Internal Medicine, 137(7), 581–585. https://doi.org/10.7326/0003-4819-137-7-200210010-00009

    Article  PubMed  Google Scholar 

  29. Leplège, A., Ecosse, E., Coste, J., Pouchot, J., & Perneger, T. (2001). Le questionnaire MOS SF-36: manuel de l’utilisateur et guide d’interprétation des scores. Éditions ESTEM.

    Google Scholar 

  30. Ware, J. E., & Gandek, B. (1998). Overview of the SF-36 health survey and the international quality of life assessment (IQOLA) project. Journal of Clinical Epidemiology, 51(11), 903–912. https://doi.org/10.1016/s0895-4356(98)00081-x

    Article  PubMed  Google Scholar 

  31. Ware, J. E., & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care, 30(6), 473–483.

    Article  PubMed  Google Scholar 

  32. Ware, J. E., Kosinski, M., & Keller, S. D. (1994). SF-36 Physical and Mental Health Summary Scales: A Users’ Manual. The Health Institute.

    Google Scholar 

  33. Riesco, E., Tessier, S., Pérusse, F., Turgeon, S., Tremblay, A., Weisnagel, J., Doré, J., & Mauriège, P. (2010). Impact of walking on eating behaviors and quality of life of premenopausal and early postmenopausal obese women. Menopause, 17(3), 529–538. https://doi.org/10.1097/gme.0b013e3181d12361

    Article  PubMed  Google Scholar 

  34. Ware, J. E., & Kosinski, M. (2001). Interpreting SF-36 summary health measures: a response. Quality of Life Research, 10(5), 405–413. https://doi.org/10.1023/a:1012588218728. discussion 415-420.

    Article  CAS  PubMed  Google Scholar 

  35. Add-Ins, J. (2014). Full Factorial Repeated Measures ANOVA Add-In. Retrieved 11/11 from https://community.jmp.com/t5/JMP-Add-Ins/Full-Factorial-Repeated-Measures-ANOVA-Add-In/ta-p/23904?trMode=source

  36. Berent, T., Berent, R., Steiner, S., & Sinzinger, H. (2019). Statin-induced muscular side effects at rest and exercise—An anatomical mapping. Atherosclerosis Supplements, 40, 73–78. https://doi.org/10.1016/j.atherosclerosissup.2019.08.026

    Article  PubMed  Google Scholar 

  37. Finegold, J. A., Manisty, C. H., Goldacre, B., Barron, A. J., & Francis, D. P. (2014). What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. European journal of preventive cardiology, 21(4), 464–474. https://doi.org/10.1177/2047487314525531

    Article  PubMed  Google Scholar 

  38. Gupta, A., Thompson, D., Whitehouse, A., Collier, T., Dahlof, B., Poulter, N., Collins, R., & Sever, P. (2017). Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian cardiac outcomes trial—lipid-lowering Arm (ASCOT-LLA): A randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. The Lancet, 389(10088), 2473–2481. https://doi.org/10.1016/s0140-6736(17)31075-9

    Article  CAS  Google Scholar 

  39. Howard, J. P., Wood, F. A., Finegold, J. A., Nowbar, A. N., Thompson, D. M., Arnold, A. D., Rajkumar, C. A., Connolly, S., Cegla, J., Stride, C., Sever, P., Norton, C., Thom, S. A. M., Shun-Shin, M. J., & Francis, D. P. (2021). Side effect patterns in a crossover trial of statin, placebo, and no treatment. Journal of the American College of Cardiology, 78(12), 1210–1222. https://doi.org/10.1016/j.jacc.2021.07.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cruz, A. C., & Pedreira, M. (2020). Patient-and Family-Centered Care and Patient Safety: reflections upon emerging proximity. Revista Brasileira de Enfermagem, 73(6), e20190672. https://doi.org/10.1590/0034-7167-2019-0672

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank all participants.

Funding

The study was supported by the Canadian Institutes of Health Research (CIHR grant MOP 114917 to DRJ, JB, and JF).

Author information

Authors and Affiliations

  1. Department of Kinesiology, Université Laval, Québec, QC, G1V 0A6, Canada

    P. Peyrel, P. Mauriège, C. Huth & D. R. Joanisse

  2. Research Center of the University Institute of Cardiology and Pulmonology of Québec, Québec, QC, G1V 4G5, Canada

    P. Peyrel, P. Mauriège, C. Huth & D. R. Joanisse

  3. CHU de Québec—Université Laval Research Center, Québec, QC, G1V 4G2, Canada

    J. Frenette, N. Laflamme, K. Greffard & J. Bergeron

  4. Department of Rehabilitation, Université Laval, Québec, QC, G1V 0A6, Canada

    J. Frenette

  5. Department of Laboratory Medicine and of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada

    J. Bergeron

Authors
  1. P. Peyrel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Mauriège
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Frenette
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Laflamme
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Greffard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Huth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Bergeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. R. Joanisse
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DRJ, JF, and JB designed the study. NL and KG provided clinical coordination, CH participated in data collection, CH managed data validation and entry, and PP, CH, and DRJ performed statistical analyses. All participated in data interpretation. PP, under the direction of DRJ and PM, wrote the manuscript. All authors critically reviewed and accepted the final version of the article.

Corresponding author

Correspondence to D. R. Joanisse.

Ethics declarations

Competing interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The protocol was approved by the CHU de Québec—Université Laval ethics committee. All patients provided written informed consent, and the study design complied with the principles of the Declaration of Helsinki and was registered in clinicaltrials.gov (NCT01493648).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 111 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peyrel, P., Mauriège, P., Frenette, J. et al. Statin withdrawal and health-related quality of life in a primary cardiovascular prevention cohort. Qual Life Res 32, 1943–1954 (2023). https://doi.org/10.1007/s11136-023-03362-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11136-023-03362-9

Keywords

Search

Navigation