The effectiveness of statins in secondary prevention of peripheral arterial disease (PAD) largely depends on patients' adherence to treatment. The aims of our study were: (a) to analyze non-adherence during the whole follow-up in persistent patients, and only during persistence for non-persistent patients; (b) to identify factors associated with non-adherence separately among persistent and non-persistent patients. A cohort of 8330 statin users aged ≥65 years, in whom PAD was newly diagnosed between January 2012-December 2012, included 5353 patients persistent with statin treatment, and 2977 subjects who became non-persistent during the 5-year follow-up. Non-adherence was defined using the proportion of days covered <80%. Patient- and statin-related characteristics associated with non-adherence were identified with binary logistic regression. A significantly higher proportion of non-adherent patients was found among non-persistent patients compared to persistent subjects (43.6% vs. 29.6%; p < 0.001). Associated with non-adherence in both persistent and non-persistent patients was high intensity statin treatment, while in non-persistent patients, it was employment and increasing number of medications. In patients with a poor adherence during their persistent period, an increased risk for discontinuation may be expected. However, there is also non-adherence among persistent patients. There are differences in factors associated with non-adherence depending on patients' persistence.

1st Department of Internal Medicine Faculty of Medicine Comenius University 813 69 Bratislava Slovakia

Department of Angiology Health Centre 917 01 Trnava Slovakia

Department of Organisation and Management of Pharmacy Faculty of Pharmacy Comenius University 832 32 Bratislava Slovakia

Department of Pharmacology Faculty of Medicine and Dentistry Palacky University 775 15 Olomouc Czech Republic

General Health Insurance Company 851 04 Bratislava Slovakia

Institute of Biomedicine University of Turku 20014 Turku Finland

Institute of Measurement Science Slovak Academy of Sciences 841 04 Bratislava Slovakia

Institute of Medical Physics Biophysics Informatics and Telemedicine Faculty of Medicine Comenius University 813 72 Bratislava Slovakia

Institute of Pharmacology and Clinical Pharmacology Faculty of Medicine Comenius University 811 08 Bratislava Slovakia

School of Pharmacy University of Eastern Finland 70211 Kuopio Finland

Zobrazit více v PubMed

Dua A., Lee C.J. Epidemiology of Peripheral Arterial Disease and Critical Limb Ischemia. Tech. Vasc. Interv. Radiol. 2016;19:91–95. doi: 10.1053/j.tvir.2016.04.001. PubMed DOI

Norgren L., Hiatt W.R., Dormandy J.A., Nehler M.R., Harris K.A., Fowkes F.G.R., TASC II Working Group Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) J. Vasc. Surg. 2007;45:S5–S67. doi: 10.1016/j.jvs.2006.12.037. PubMed DOI

Markel A. Statins and peripheral arterial disease. Int. Angiol. 2015;34:416–427. PubMed

Morley R.L., Sharma A., Horsch A.D., Hinchliffe R.J. Peripheral artery disease. BMJ. 2018;360:j5842. doi: 10.1136/bmj.j5842. PubMed DOI

Firnhaber J.M., Powell C.S. Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment. Am. Fam. Physician. 2019;99:362–369. PubMed

European Stroke Organisation. Tendera M., Aboyans V., Bartelink M.-L., Baumgartner I., Clément D., Collet J.-P., Cremonesi A., De Carlo M., Erbel R., 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;32:2851–2906. doi: 10.1093/eurheartj/ehr211. PubMed DOI

Kumbhani D.J., Steg P.G., Cannon C.P., Eagle K.A., Smith S.C., Jr., Goto S., Ohman E.M., Elbez Y., Sritara P., Baumgartner I., et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: Insights from the REACH registry. Eur. Heart J. 2014;35:2864–2872. doi: 10.1093/eurheartj/ehu080. PubMed DOI PMC

Mohler E.R., 3rd, Hiatt W.R., Creager M.A. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108:1481–1486. doi: 10.1161/01.CIR.0000090686.57897.F5. PubMed DOI

De Geest S., Zullig L.L., Dunbar-Jacob J., Helmy R., Hughes D.A., Wilson I.B., Vrijens B. ESPACOMP Medication Adherence Reporting Guideline (EMERGE) Ann. Intern. Med. 2018;169:30–35. doi: 10.7326/M18-0543. PubMed DOI PMC

Vrijens B., De Geest S., Hughes D.A., Przemyslaw K., Demonceau J., Ruppar T., Dobbels F., Fargher E., Morrison V., Lewek P., et al. A new taxonomy for describing and defining adherence to medications. Br. J. Clin. Pharmacol. 2012;73:691–705. doi: 10.1111/j.1365-2125.2012.04167.x. PubMed DOI PMC

Wawruch M., Wimmer G., Jr., Murin J., Paduchova M., Tesar T., Hlinkova L., Slavkovsky P., Fabryova L., Aarnio E. Patient-Associated Characteristics Influencing the Risk for Non-Persistence with Statins in Older Patients with Peripheral Arterial Disease. Drugs Aging. 2019;36:863–873. doi: 10.1007/s40266-019-00689-2. PubMed DOI

Giardini A., Martin M.T., Cahir C., Lehane E., Menditto E., Strano M., Pecorelli S., Monaco A., Marengoni A. Toward appropriate criteria in medication adherence assessment in older persons: Position Paper. Aging Clin. Exp. Res. 2016;28:371–381. doi: 10.1007/s40520-015-0435-z. PubMed DOI

Gregoire J.P., Moisan J. Assessment of adherence to drug treatment in database research. In: Elseviers M., editor. Drug Utilization Research: Methods and Applications. 1st ed. John Wiley & Sons; Hoboken, NJ, USA: 2016. pp. 369–380.

Peterson A.M., Nau D.P., Cramer J.A., Benner J., Gwadry-Sridhar F., Nichol M. A checklist for medication compliance and persistence studies using retrospective databases. Value Health. 2007;10:3–12. doi: 10.1111/j.1524-4733.2006.00139.x. PubMed DOI

Aarnio E., Martikainen J., Helin-Salmivaara A., Huupponen R.K., Hartikainen J.E., Peura P.K., Korhonen M.J. Register-based predictors of adherence among new statin users in Finland. J. Clin. Lipidol. 2014;8:117–125. doi: 10.1016/j.jacl.2013.09.008. PubMed DOI

Korhonen M.J., Helin-Salmivaara A., Huupponen R. Dynamics of long-term statin therapy. Eur. J. Clin. Pharmacol. 2011;67:925–931. doi: 10.1007/s00228-011-1019-2. PubMed DOI

Alfian S.D., Worawutputtapong P., Schuiling-Veninga C.C.M., van der Schans J., Bos J.H.J., Hak E., Denig P. 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;34:1013–1019. doi: 10.1080/03007995.2017.1417242. PubMed DOI

Alfian S.D., Denig P., Coelho A., Hak E. Pharmacy-based predictors of non-adherence, non-persistence and reinitiation of antihypertensive drugs among patients on oral diabetes drugs in the Netherlands. PLoS ONE. 2019;14:e0225390. doi: 10.1371/journal.pone.0225390. PubMed DOI PMC

Bohensky M., Tacey M., Brand C., Sundararajan V., Wicks I., Van Doornum S. Statin initiation and treatment non-adherence following a first acute myocardial infarction in patients with inflammatory rheumatic disease versus the general population. Arthritis Res. Ther. 2014;16:443–451. doi: 10.1186/s13075-014-0443-y. PubMed DOI PMC

Muntner P., Yun H., Sharma P., Delzell E., Kent S.T., Kilgore M.L., Farkouh M.E., Vupputuri S., Bittner V., Rosenson R.S., 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;114:826–831. doi: 10.1016/j.amjcard.2014.06.009. PubMed DOI

Wawruch M., Zatko D., Wimmer G., Jr., Luha J., Wimmerova S., Matalova P., Kukumberg P., Murin J., Tesar T., Havelkova B., et al. Age-Related Differences in Non-Persistence with Statin Treatment in Patients after a Transient Ischaemic Attack. Clin. Drug Investig. 2017;37:1047–1054. doi: 10.1007/s40261-017-0559-3. PubMed DOI

Wawruch M., Zatko D., Wimmer G., Jr., Luha J., Hricak V., Jr., Murin J., Kukumberg P., Tesar T., Hloska A., Shah R. Patient-related characteristics associated with non-persistence with statin therapy in elderly patients following an ischemic stroke. Pharmacoepidemiol. Drug Saf. 2017;26:201–207. doi: 10.1002/pds.4148. PubMed DOI

Romppainen T., Rikala M., Aarnio E., Korhonen M.J., Saastamoinen L.K., Huupponen R. Measurement of statin exposure in the absence of information on prescribed doses. Eur. J. Clin. Pharmacol. 2014;70:1275–1276. doi: 10.1007/s00228-014-1737-3. PubMed DOI

Karve S., Cleves M.A., Helm M., Hudson T.J., West D.S., Martin B.C. Good and poor adherence: Optimal cut-point for adherence measures using administrative claims data. Curr. Med. Res. Opin. 2009;25:2303–2310. doi: 10.1185/03007990903126833. PubMed DOI

Newman S.C. Biostatistical Methods in Epidemiology. Wiley; Chichester, UK: 2001. p. 382.

Warren J.R., Falster M.O., Fox D., Jorm L. Factors influencing adherence in long-term use of statins. Pharmacoepidemiol. Drug Saf. 2013;22:1298–1307. doi: 10.1002/pds.3526. PubMed DOI

Ofori-Asenso R., Ilomäki J., Tacey M., Curtis A.J., Zomer E., Bell J.S., 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;33:527–534. doi: 10.1177/1533317518787314. PubMed DOI PMC

Gellad W.F., Grenard J.L., Marcum Z.A. A systematic review of barriers to medication adherence in the elderly: Looking beyond cost and regimen complexity. Am. J. Geriatr. Pharmacother. 2011;9:11–23. doi: 10.1016/j.amjopharm.2011.02.004. PubMed DOI PMC

Ofori-Asenso R., Ilomäki J., Tacey M., Si S., Curtis A.J., Zomer E., Bell J.S., Zoungas S., Liew D. Predictors of first-year nonadherence and discontinuation of statins among older adults: A retrospective cohort study. Br. J. Clin. Pharmacol. 2019;85:227–235. doi: 10.1111/bcp.13797. PubMed DOI PMC

Lemstra M., Blackburn D., Crawley A., Fung R. Proportion and risk indicators of nonadherence to statin therapy: A meta-analysis. Can. J. Cardiol. 2012;28:574–580. doi: 10.1016/j.cjca.2012.05.007. PubMed DOI

Wouters H., Van Dijk L., Geers H.C., Winters N.A., Van Geffen E.C., Stiggelbout A.M., Bouvy M.L. Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients. PLoS ONE. 2016;11:e0146272. doi: 10.1371/journal.pone.0146272. PubMed DOI PMC

Ofori-Asenso R., Jakhu A., Curtis A.J., Zomer E., Gambhir M., Korhonen M.J., Nelson M., Tonkin A., Liew D., Zoungas S. 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;73:798–805. doi: 10.1093/gerona/glx256. PubMed DOI

Charlson M.E., Pompei P., Ales K.L., MacKenzie C.R. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J. Chronic Dis. 1987;40:373–383. doi: 10.1016/0021-9681(87)90171-8. PubMed DOI

Adherence to Antiplatelet Medications among Persistent and Non-Persistent Older Patients with Peripheral Arterial Disease