Assessing the Adherence to and the Therapeutic Effectiveness of Hypolipidemic Agents in a Population of Patients in Brazil: a Retrospective Cohort Study
Objective: to evaluate the relation between patient adherence and therapeutic effectiveness of hypolipemiant agents in clinical practice.
Methods: A retrospective study of 417 patients using hypolipemiant drugs (simvastatin, atorvastatin) between 2003 and 2010 was performed. The study population consisted in patients assisted by the Public Health Service in the far-west region of the State of Santa Catarina, Brazil. The Medication Possession Ratio obtained from pharmacy refill data was used to measure patient adherence. Therapeutic effectiveness was evaluated based on the difference obtained in the serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides, before and after taking the drug, in an average time of 8.3 months.
Results: Following the treatment with hypolipemiant agents, it has been observed a reduction of 14.3% for total cholesterol, 19.6% for LDL-cholesterol, and 14.4% for triglycerides. HDL-cholesterol increased by an 8.0% average. Atorvastatin 20 mg daily promoted the major changes in lipid profile. The medication adherence rate decreased over the monitoring period. Rates of compliance below 60% were associated with therapeutic failure, while rates equal to 80% or higher were associated with the best response to the lipid-lowering drugs.
Conclusion: Adherence to hypolipemiant agents is higher at the beginning of the treatment, but it decreases over time, affecting the achievement of therapeutic goals. The adoption by the pharmacist of actions to monitoring patient compliance to pharmacy refills can be helpful to identify patient at high risk for therapeutic failure and can potentially improve treatment success.
2 Sposito AC, Caramelli B, Fonseca FA, Bertolami MC, Afiune Neto A, Souza AD, Lottenberg AM, Chacra AP, Faludi AA, Loures-Vale AA, Carvalho AC, Duncan B, Gelonese B, Polanczyk C, Rodrigues Sobrinho CR, Scherr C, Karla C, Armaganijan D, Moriguchi E, Saraiva F, Pichetti G, Xavier HT, Chaves H, Borges JL, Diament J, Guimarães JI, Nicolau JC, dos Santos JE, de Lima JJ, Vieira JL, Novazzi JP, Faria Neto JR, Torres KP, Pinto Lde A, Bricarello L, Bodanese LC, Introcaso L, Malachias MV, Izar MC, Magalhães ME, Schmidt MI, Scartezini M, Nobre M, Foppa M, Forti NA, Berwanger O, Gebara OC, Coelho OR, Maranhão RC, dos Santos Filho RD, Costa RP, Barreto S, Kaiser S, Ihara S, Carvalho Td, Martinez TL, Relvas WG, Salgado W; Sociedade Brasileira de Cardiologia. [IV Brazilian Guideline for Dyslipidemia and Atherosclerosis prevention: Department of Atherosclerosis of Brazilian Society of Cardiology]. Arq Bras Cardiol. 2007;88(Suppl 1):2-19.
3 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-2497.
4 Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC, Fonseca FA, dos Santos JE, Santos RD, Bertolami MC, Faludi AA, Martinez TL, Diament J, Guimarães A, Forti NA, Moriguchi E, Chagas AC, Coelho OR, Ramires JA. V Diretriz brasileira de dislipidemia e prevenção da aterosclerose. Arq Bras Cardiol. 2013 Oct;101(4 Suppl 1):1-20. doi: 10.5935/abc.2013S010
5 Olson KL, Potts LA. Role of the pharmacist in the management of dyslipidemia. J Pharm Pract. 2006;19(2):94-102. doi: 10.1177/0897190006290046
6 Ward S, Lloyd Jones M, Pandor A, Holmes M, Ara R, Ryan A, Yeo W, Payne N. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess. 2007;11(14):1-160.
7 Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; Cholesterol Treatment Trialists' (CTT) Collaborators. 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):1267-1278.
8 Li ZY, Tang TY, Jiang F, Zhang Y, Gillard JH. Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease. Circ J. 2011;75(6):1486-1492.
9 Sposito AR, Aguiar Filho GB, Aarão AR, Sousa FTT, Bertolami MC. Statins in acute coronary syndromes. Arq Bras Cardiol. 2011;97(4):350-356.
10 Leite SN, Vasconcellos MPC. Adherence to prescribed therapy: points for concepts and presuppositions discussion. Cienc Saude Coletiva. 2003;8(3):775-782.
11 Fikri-Benbrahim N, García-Cárdenas V, Sáez-Benito L, Gastelurrutia MA, Faus MJ. Adherence: a review of education, research, practice and policy in Spain. Pharm Pract (Granada). 2009;7(3):125-138.
12 WHO. Adherence to long-term therapies. Evidence for actions. Geneve: World health Organization. 2003 http://www.who.int/chp/knowledge/publications/adherence_report/en/ (accessed 3-29-2014).
13 Schneider MP, Krummenacher I, Figueiredo H, Marquis J, Bugnon O. Adherence: a review of education, research, practice and policy in Switzerland. Pharm Pract (Granada). 2009;7(2):63-73.
14 Haugbølle LS, Herborg H. Adherence to treatment: practice, education and research in Danish community pharmacy. Pharm Pract (Granada). 2009;7(4):185-194.
15 Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med. 2005;353(5):487-497.
16 Cooper J, Hall L, Penland A, Krueger A, May J. Measuring medication adherence. Popul Health Manag. 2009;12(1):25-30.
17 Dezii CM. Persistence with drug therapy: a practical approach using administrative claims data. Manag Care. 2001;10(2):42-45.
18 Haynes RB, McDonald HP, Garg AX. Helping patients follow prescribed treatment: clinical applications. JAMA. 2002;288(22):2880-2883.
19 Mabotuwana T, Warren J, Harrison J, Kenealy T. What can primary care prescribing data tell us about individual adherence to long-term medication? - Comparison to pharmacy dispensing data. Pharmacoepidemiol Drug Saf. 2009;18(10):956-964. doi: 10.1002/pds.1803
20 Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24(1):67-74.
21 Aslani P, Krass I. Adherence: a review of education, research, practice and policy in Australia. Pharm Pract (Granada). 2009;7(1):1-10.
22. Mauskop A, Borden WB. Predictors of statin adherence. Curr Cardiol Rep. 2011;13(6):553-558. doi: 10.1007/s11886-011-0221-2
23. Catalan VS, LeLorier J. Predictors of long-term persistence on statins in a subsidized clinical population. Value Health. 2000;3(6):417-426.
24 Rickles NM, Brown TA, McGivney MS, Snyder ME, White KA. Adherence: a review of education, research, practice, and policy in the United States. Pharm Pract (Granada). 2010;8(1):1-17.
25 Thunander Sundbom L, Bingefors K. Women and men report different behaviours in, and reasons for medication nonadherence:a nationwide Swedish survey. Pharm Pract (Granada). 2012;10(4):207-221.
26 Mangan MN, Powers MF, Lengel AJ. Student Pharmacists' Perceptions of Barriers to Medication Adherence Counseling J Pharm Pract. 2013 Aug;26(4):376-381. doi: 10.1177/0897190012466896
27 Schneider MP, Aslani P. Adherence policy, education and practice - an international perspective. Pharm Pract (Granada). 2010;8(4):209-212.
28 BRASIL. Ministério da Saúde. Secretaria de Assistência à Saúde. Portaria nº 1.015 de 23 de dezembro de 2002. Aprova o Protocolo Clínico e Diretrizes Terapêuticas para as Dislipidemias em pacientes de alto risco de desenvolver eventos cardiovasculares. Diário Oficial da União, Brasília, DF, 24 dez. 2002.
29 Santos RD, Giannini SD, Fonseca FH, Moriguchi EH: Sociedade Brasileira de Cardiologia. III Diretrizes brasileiras sobre dislipidemias e diretriz de prevenção da aterosclerose do Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2001;77(supl 3):1-48.
30 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):582-587.
31 Brown AS, Bakker-Arkema RG, Yellen L, Henley RW Jr, Guthrie R, Campbell CF, Koren M, Woo W, McLain R, Black DM. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol. 1998;32(3):665-672.
32 Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med. 2001;111(3):185-191.
33 Shalansky SJ, Levy RA, Ignaszewski AP. Self-reported morisky score for identifying nonadherende with cardiovascular medications. Ann Pharmacother. 2004;38(9):1363-1368.
34 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):455-461.
35 Ruokoniemi P, Korhonen MJ, Helin-Salmivaara A, Lavikainen P, Jula A, Junnila SY, Kettunen R, Huupponen R. Statin adherence and the risk of major coronary events in patients with diabetes: a nested case–control study. Br J Clin Pharmacol. 2011;71(5):766-776. doi: 10.1111/j.1365-2125.2010.03895.x
36 Andrade SE, Walker AM, Gottlieb LK, Hollenberg NK, Testa MA, Saperia GM, Platt R. Discontinuation of antihyperlipidemic drugs - do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med. 1995;332(17):1125-1131.
37 Applegate WB. Elderly patients' adherence to statin therapy. JAMA. 2002;288(4):495-497.
38 Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288(4):462-467.
39. Avorn J, Monette J, Lacour A, Bohn RL, Monane M, Mogun H, LeLorier J. Persistence of use of lipid-lowering medications. A Cross-National Study. JAMA. 1998;279(18):1458-1462.
40 Eussen SR, van der Elst ME, Klungel OH, Rompelberg CJ, Garssen J, Oosterveld MH, de Boer A, de Gier JJ, Bouvy ML. A pharmaceutical care program to improve adherence to statin therapy: a randomized controlled trial. Ann Pharmacother. 2010;44(12):1905-1913. doi: 10.1345/aph.1P281
41 Giberson S, Yoder S, Lee MP. Improving Patient and Health System Outcomes through Advanced Pharmacy Practice. A Report to the U.S. Surgeon General. Office of the Chief Pharmacist. U.S. Public Health Service, 2011.
42 Murray MD, Ritchey ME, Wu J, Tu W. Effect of a pharmacist on adverse drug events and medication errors in outpatients with cardiovascular disease. Arch Intern Med. 2009;169(8):757-763. doi: 10.1001/archinternmed.2009.59
43 Machado M, Nassor N, Bajcar JM, Guzzo GC, Einarson TR. Sensitivity of patient outcomes to pharmacist interventions. Part III: systematic review and meta-analysis in hyperlipidemia management. Ann Pharmacother. 2008;42(9):1195-1207. doi: 10.1345/aph.1K618
44 Odum L, Whaley-Connell A. The role of team-based care involving pharmacists to improve cardiovascular and renal outcomes. Cardiorenal Med. 2012;2(4):243-250.
45 Shoulders BR, Franks AS, Barlow PB, Williams JD, Farland MZ. Impact of pharmacists' interventions and simvastatin dose restrictions. Ann Pharmacother. 2014;48(1):54-61. doi: 10.1177/1060028013511323
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