Skip to main content
SpringerLink
Log in

Patient-Associated Characteristics Influencing the Risk for Non-Persistence with Statins in Older Patients with Peripheral Arterial Disease

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background and Objectives

Secondary prevention of peripheral arterial disease includes administration of statins regardless of the patient’s serum cholesterol level. Our study aimed to identify patient-associated risk factors for statin non-persistence and comparison of the explanatory power of models based on clusters of patient-associated characteristics.

Methods

Our study cohort (n = 8330) was assembled from the database of the largest health insurance provider in the Slovak Republic. Statin users aged ≥ 65 years in whom peripheral arterial disease was diagnosed during 2012 were included. Patients were followed for 5 years; those with a treatment gap period of at least 6 months without statin prescription were classified as “non-persistent”. The risk factors for non-persistence were identified within six models (sociodemographic, cardiovascular events, comorbid conditions, statin-related characteristics, cardiovascular co-medication and full model) using Cox regression. The explanatory power of models was assessed using Harrell’s C-index.

Results

At the end of the follow-up, 35.7% of patients were found to be non-persistent. The full model had the highest explanatory power (C = 0.632). Female sex, atorvastatin and rosuvastatin as initially administered statins, being a new statin user and an increasing co-payment were associated with an increased risk for non-persistence. Increasing age, history of ischaemic stroke, diabetes mellitus, general practitioner as index prescriber, increasing overall number of medications and co-administration of certain cardiovascular co-medications were associated with a lower likelihood for non-persistence.

Conclusions

Patients identified as high risk for non-persistence require special attention aimed at the improvement of their persistence with statin treatment.

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

Similar content being viewed by others

References

  1. Coppola G, Novo S. Statins and peripheral arterial disease: effects on claudication, disease progression, and prevention of cardiovascular events. Arch Med Res. 2007;38(5):479–88.

    Article  CAS  PubMed  Google Scholar 

  2. Kalbaugh CA, Kucharska-Newton A, Wruck L, et al. Peripheral artery disease prevalence and incidence estimated from both outpatient and inpatient settings among Medicare fee-for-service beneficiaries in the Atherosclerosis Risk in Communities (ARIC) Study. J Am Heart Assoc. 2017;6(5):1–9.

    Article  Google Scholar 

  3. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc. 1985;33(1):13–8.

    Article  CAS  PubMed  Google Scholar 

  4. Tendera M, Aboyans V, Bartelink ML, et al. ESC guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. The Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(22):2851–906.

  5. Markel A. Statins and peripheral arterial disease. Int Angiol. 2015;34(5):416–27.

    CAS  PubMed  Google Scholar 

  6. Bonaca MP, Creager MA. Pharmacological treatment and current management of peripheral artery disease. Circ Res. 2015;116(9):1579–98.

    Article  CAS  PubMed  Google Scholar 

  7. Endres M. Statins and stroke. J Cereb Blood Flow Metab. 2005;25(9):1093–110.

    Article  CAS  PubMed  Google Scholar 

  8. Burton JK, Papworth R, Haig C, et al. Statin use is not associated with future long-term care admission: extended follow-up of two randomised controlled trials. Drugs Aging. 2018;35(7):657–63.

    Article  CAS  PubMed  Google Scholar 

  9. Thompson W, Pottegård A, Nielsen JB, Haastrup P, Jarbøl DE. How common is statin use in the oldest old? Drugs Aging. 2018;35(8):679–86.

    Article  CAS  PubMed  Google Scholar 

  10. Westin GG, Armstrong EJ, Bang H, et al. Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia. J Am Coll Cardiol. 2014;63(7):682–90.

    Article  CAS  PubMed  Google Scholar 

  11. Yandrapalli S, Gupta S, Andries G, Cooper HA, Aronow WS. Drug therapy of dyslipidemia in the elderly. Drugs Aging. 2019;36(4):321–40.

    Article  CAS  PubMed  Google Scholar 

  12. De Geest S, Zullig LL, Dunbar-Jacob J, et al. ESPACOMP medication adherence reporting guideline (EMERGE). Ann Intern Med. 2018;169(1):30–5.

    Article  PubMed  Google Scholar 

  13. Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73(5):691–705.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ofori-Asenso R, Jakhu A, Zomer E, Curtis AJ, Korhonen MJ, Nelson M, et al. Adherence and persistence among statin users aged 65 years and over: a systematic review and meta-analysis. J Gerontol A Biol Sci Med Sci. 2018;73(6):813–9.

    Article  PubMed  Google Scholar 

  15. Ofori-Asenso R, Jakhu A, Curtis AJ, et al. A systematic review and meta-analysis of the factors associated with nonadherence and discontinuation of statins among people aged ≥ 65 years. J Gerontol A Biol Sci Med Sci. 2018;73(6):798–805.

    Article  PubMed  Google Scholar 

  16. Booth JN 3rd, Colantonio LD, Chen L, et al. Statin discontinuation, reinitiation, and persistence patterns among Medicare beneficiaries after myocardial infarction: a cohort study. Circ Cardiovasc Qual Outcomes. 2017;10(10):1–9.

    Article  Google Scholar 

  17. Daskalopoulou SS, Delaney JA, Filion KB, Brophy JM, Mayo NE, Suissa S. Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J. 2008;29(17):2083–91.

    Article  PubMed  Google Scholar 

  18. Muntner P, Yun H, Sharma P, et al. Ability of low antihypertensive medication adherence to predict statin discontinuation and low statin adherence in patients initiating treatment after a coronary event. Am J Cardiol. 2014;114(6):826–31.

    Article  PubMed  Google Scholar 

  19. Wawruch M, Zatko D, Wimmer G Jr, et al. Patient-related characteristics associated with non-persistence with statin therapy in elderly patients following an ischemic stroke. Pharmacoepidemiol Drug Saf. 2017;26(2):201–7.

    Article  CAS  PubMed  Google Scholar 

  20. Wawruch M, Zatko D, Wimmer G Jr, et al. Age-related differences in non-persistence with statin treatment in patients after a transient ischaemic attack. Clin Drug Investig. 2017;37(11):1047–54.

    Article  CAS  PubMed  Google Scholar 

  21. Romppainen T, Rikala M, Aarnio E, Korhonen MJ, Saastamoinen LK, Huupponen R. Measurement of statin exposure in the absence of information on prescribed doses. Eur J Clin Pharmacol. 2014;70(10):1275–6.

    Article  PubMed  Google Scholar 

  22. International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Geneva: WHO; 1992. p. 191.

  23. Stone NJ, Robinson JG, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl. 2):S1–45.

    Article  PubMed  Google Scholar 

  24. Guidelines for ATC classification and DDD assignment 2018. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2018. p. 283.

  25. Newman SC. Biostatistical methods in epidemiology. Chichester: Wiley; 2001. p. 382.

    Google Scholar 

  26. Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87.

    Article  PubMed  Google Scholar 

  27. Uno H, Cai T, Pencina MJ, D’Agostino RB, Wei LJ. On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med. 2011;30(10):1105–17.

    PubMed  PubMed Central  Google Scholar 

  28. Baroletti S, Dell’Orfano H. Medication adherence in cardiovascular disease. Circulation. 2010;121(12):1455–8.

    Article  PubMed  Google Scholar 

  29. Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J Clin Lipidol. 2013;7(5):472–83.

    Article  PubMed  Google Scholar 

  30. Alfian SD, Worawutputtapong P, Schuiling-Veninga CCM, et al. Pharmacy-based predictors of non-persistence with and non-adherence to statin treatment among patients on oral diabetes medication in the Netherlands. Curr Med Res Opin. 2018;34(6):1013–9.

    Article  CAS  PubMed  Google Scholar 

  31. Goldstein KM, Zullig LL, Bastian LA, Bosworth HB. Statin adherence: does gender matter? Curr Atheroscler Rep. 2016;18(11):63.

    Article  CAS  PubMed  Google Scholar 

  32. Miller P. Women and cardiovascular disease: what can health care providers do to reduce the risks? N C Med J. 2016;77(6):406–9.

    PubMed  Google Scholar 

  33. National Clinical Guideline Centre (UK). MI: secondary prevention. Secondary prevention in primary and secondary care for patients following a myocardial infarction: partial update of NICE CG48. London: Royal College of Physicians (UK); 2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK247688/. Accessed 1 Mar 2019.

  34. Arnan MK, Burke GL, Bushnell C. Secondary prevention of stroke in the elderly: focus on drug therapy. Drugs Aging. 2014;31(10):721–30.

    Article  CAS  PubMed  Google Scholar 

  35. Ofori-Asenso R, Ilomaki J, Tacey M, Zomer E, Curtis AJ, Si S, et al. Switching, discontinuation, and reinitiation of statins among older adults. J Am Coll Cardiol. 2018;72(21):2675–7.

    Article  PubMed  Google Scholar 

  36. O’Shea MP, Teeling M, Bennett K. Regional variation in medication-taking behaviour of new users of oral anti-hyperglycaemic therapy in Ireland. Ir J Med Sci. 2015;184(2):403–10.

    Article  CAS  PubMed  Google Scholar 

  37. Helin-Salmivaara A, Lavikainen P, Ruokoniemi P, Korhonen M, Huupponen R. Persistence with statin therapy in diabetic and non-diabetic persons: a nation-wide register study in 1995–2005 in Finland. Diabetes Res Clin Pract. 2009;84(1):e9–11.

    Article  PubMed  Google Scholar 

  38. Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288(4):455–61.

    Article  PubMed  Google Scholar 

  39. Ofori-Asenso R, Ilomaki J, Tacey M, Curtis AJ, Zomer E, Bell JS, Zoungas S, Liew D. Prevalence and incidence of statin use and 3-year adherence and discontinuation rates among older adults with dementia. Am J Alzheimers Dis Other Demen. 2018;33(8):527–34.

    Article  PubMed  Google Scholar 

  40. Ofori-Asenso R, Ilomäki J, Tacey M, et al. Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study. Br J Clin Pharmacol. 2019;85(1):227–35.

    Article  PubMed  Google Scholar 

  41. Ponikowski P, Voors AA, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975.

  42. Ofori-Asenso R, Ilomäki J, Tacey M, et al. Patterns of statin use and long-term adherence and persistence among older adults with diabetes. J Diabetes. 2018;10(9):699–707.

    Article  CAS  PubMed  Google Scholar 

  43. Citarella A, Kieler H, Sundström A, et al. Family history of cardiovascular disease and influence on statin therapy persistence. Eur J Clin Pharmacol. 2014;70(6):701–7.

    Article  CAS  PubMed  Google Scholar 

  44. Watanabe JH, Kazerooni R, Bounthavong M. Association of copayment with likelihood and level of adherence in new users of statins: a retrospective cohort study. J Manag Care Pharm. 2014;20(1):43–50.

    PubMed  Google Scholar 

  45. Aarnio EJ, Martikainen JA, Helin-Salmivaara A, et al. Register-based predictors of adherence among new statin users in Finland. J Clin Lipidol. 2014;8(1):117–25.

    Article  PubMed  Google Scholar 

  46. Morotti K, Lopez J, Vaupel V, Swislocki A, Siegel D. Adherence to and persistence with statin therapy in a veteran population. Ann Pharmacother. 2019;53(1):43–9.

    Article  PubMed  Google Scholar 

  47. Grant RW, O’Leary KM, Weilburg JB, Singer DE, Meigs JB. Impact of concurrent medication use on statin adherence and refill persistence. Arch Intern Med. 2004;164(21):2343–8.

    Article  PubMed  Google Scholar 

  48. Ofori-Asenso R, Zoungas S, Liew D. Reinitiation of statin therapy after discontinuation: a meta-analysis. Mayo Clin Proc. 2018;93(5):666–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08, Bratislava, Slovakia

    Martin Wawruch

  2. Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

    Gejza Wimmer Jr

  3. 1st Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia

    Jan Murin

  4. Department of Angiology, Health Centre, Trnava, Slovakia

    Martina Paduchova

  5. Department of Organisation and Management of Pharmacy, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32, Bratislava, Slovakia

    Tomas Tesar

  6. General Health Insurance Company, Bratislava, Slovakia

    Lubica Hlinkova

  7. Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia

    Peter Slavkovsky

  8. Department of Diabetes and Metabolic Disorders, MetabolKLINIK, Bratislava, Slovakia

    Lubomira Fabryova

  9. Biomedical Research Centre, Slovak Academy of Sciences, Bratislava, Slovakia

    Lubomira Fabryova

  10. Institute of Biomedicine, University of Turku, Turku, Finland

    Emma Aarnio

  11. School of Pharmacy, University of Eastern Finland, Kuopio, Finland

    Emma Aarnio

Authors
  1. Martin Wawruch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gejza Wimmer Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Murin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martina Paduchova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomas Tesar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lubica Hlinkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Slavkovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lubomira Fabryova
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emma Aarnio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Martin Wawruch or Tomas Tesar.

Ethics declarations

Funding

This study was supported by a grant from the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 1/0112/17. Emma Aarnio has received funding from the Finnish Cultural Foundation. The providers of these grants played no role in the study design, methodology, data collection, analysis and interpretation of the data, preparation of the paper, or in the decision to submit the manuscript.

Conflict of interest

Martin Wawruch, Gejza Wimmer Jr, Jan Murin, Martina Paduchova, Tomas Tesar, Lubica Hlinkova, Peter Slavkovsky, Lubomira Fabryova and Emma Aarnio have no conflicts of interest that are directly relevant to the content of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (RTF 131 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wawruch, M., Wimmer, G., Murin, J. et al. Patient-Associated Characteristics Influencing the Risk for Non-Persistence with Statins in Older Patients with Peripheral Arterial Disease. Drugs Aging 36, 863–873 (2019). https://doi.org/10.1007/s40266-019-00689-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-019-00689-2

Search

Navigation