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Meta-Analysis
. 2016 Dec 21;12(12):CD004371.
doi: 10.1002/14651858.CD004371.pub4.

Interventions to improve adherence to lipid-lowering medication

Mieke L van Driel  1   2 , Michael D Morledge  3 , Robin Ulep  3 , Johnathon P Shaffer  3 , Philippa Davies  4 , Richard Deichmann  5
Affiliations
Meta-Analysis

Interventions to improve adherence to lipid-lowering medication

Mieke L van Driel et al. Cochrane Database Syst Rev. .

Abstract

Background: Lipid-lowering drugs are widely underused, despite strong evidence indicating they improve cardiovascular end points. Poor patient adherence to a medication regimen can affect the success of lipid-lowering treatment.

Objectives: To assess the effects of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and CINAHL up to 3 February 2016, and clinical trials registers (ANZCTR and ClinicalTrials.gov) up to 27 July 2016. We applied no language restrictions.

Selection criteria: We evaluated randomised controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with a variety of measurable outcomes, such as adherence to treatment and changes to serum lipid levels. Two teams of review authors independently selected the studies.

Data collection and analysis: Three review authors extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the quality of the evidence using GRADEPro.

Main results: For this updated review, we added 24 new studies meeting the eligibility criteria to the 11 studies from prior updates. We have therefore included 35 studies, randomising 925,171 participants. Seven studies including 11,204 individuals compared adherence rates of those in an intensification of a patient care intervention (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) versus usual care over the short term (six months or less), and were pooled in a meta-analysis. Participants in the intervention group had better adherence than those receiving usual care (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.29 to 2.88; 7 studies; 11,204 participants; moderate-quality evidence). A separate analysis also showed improvements in long-term adherence rates (more than six months) using intensification of care (OR 2.87, 95% CI 1.91 to 4.29; 3 studies; 663 participants; high-quality evidence). Analyses of the effect on total cholesterol and LDL-cholesterol levels also showed a positive effect of intensified interventions over both short- and long-term follow-up. Over the short term, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17 to 33.14; 4 studies; 430 participants; low-quality evidence) and LDL-cholesterol decreased by a mean of 19.51 mg/dL (95% CI 8.51 to 30.51; 3 studies; 333 participants; moderate-quality evidence). Over the long term (more than six months) total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95 to 20.19; 2 studies; 127 participants; high-quality evidence). Included studies did not report usable data for health outcome indications, adverse effects or costs/resource use, so we could not pool these outcomes. We assessed each included study for bias using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. In general, the risk of bias assessment revealed a low risk of selection bias, attrition bias, and reporting bias. There was unclear risk of bias relating to blinding for most studies.

Authors' conclusions: The evidence in our review demonstrates that intensification of patient care interventions improves short- and long-term medication adherence, as well as total cholesterol and LDL-cholesterol levels. Healthcare systems which can implement team-based intensification of patient care interventions may be successful in improving patient adherence rates to lipid-lowering medicines.

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Conflict of interest statement

Mieke L van Driel declares that there is no conflict of interest.

Michael D Morledge declares that there is no conflict of interest.

Robin Ulep declares that there is no conflict of interest.

Johnathon P Shaffer declares that there is no conflict of interest.

Philippa Davies declares that there is no conflict of interest.

Richard Deichmann declares that there is no conflict of interest.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 1: Medication adherence at ≤ 6 months
1.2
1.2. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 2: Medication adherence at > 6 months
1.3
1.3. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 3: Reduction in total serum cholesterol at ≤ 6 mos (mg/dL)
1.4
1.4. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 4: Reduction in total serum cholesterol at > 6 mos (mg/dL)
1.5
1.5. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 5: Reduction in LDL‐C at ≤ 6 months (mg/dL)
1.6
1.6. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 6: Reduction in LDL‐C > 6 months (mg/dL)
1.7
1.7. Analysis
Comparison 1: Intensified patient care vs usual care, Outcome 7: Attrition rate sensitivity analysis (medication adherence at ≤ 6 months)
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Aslani 2010 {published data only}
    1. Aslani P, Rose G, Chen TF, Whitehead PA, Krass I. A community pharmacist delivered adherence support service for dyslipidaemia. European Journal of Public Health 2010;21(5):567-72. - PubMed
Brown 1997 {published data only}
    1. Brown BG, Bardsley J, Poulin D, Hillger LA, Dowdy A, Maher VM, et al. Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease. American Journal of Cardiology 1997;80(2):111-15. - PubMed
Castellano 2014 {published data only}
    1. Castellano JM, Gines S, Penalvo JL, Bansilal S, Fernandez-Ortiz A, Alvarez L, et al. A polypill strategy to improve adherence: results from the FOCUS Project. Journal of the American College of Cardiology 2014;64(20):2071-82. [DOI: 10.1016/j.jacc.2014.08.021] - DOI - PubMed
Choudhry 2011 {published data only}
    1. Choudhry NK, Avorn J, Glynn RJ, Antman EM, Schneeweiss S, Toscano M, et al. Full coverage for preventive medications after myocardial infarction. New England Journal of Medicine 2011;365(22):2088-97. - PubMed
Derose 2012 {published data only}
    1. Derose SF, Green K, Marrett E, Tunceli K, Cheetham TC, Chiu VY, et al. Automated outreach to increase primary adherence to cholesterol-lowering medications. JAMA Internal Medicine 2013;173(1):38-43. [DOI: 10.1001/2013.jamainternmed.717] - DOI - PubMed
Eussen 2010 {published data only}
    1. Eussen SR, Van der Elst ME, Klungel OH, Rompelberg CJ, Garssen J, Oosterveld MH, et al. A pharmaceutical care program to improve adherence to statin therapy: a randomized controlled trial. Annals of Pharmacotherapy 2010;44(12):1905-13. - PubMed
Fang 2015 {published data only}
    1. Fang R, Li X. Electronic messaging support service programs improve adherence to lipid‐lowering therapy among outpatients with coronary artery disease: an exploratory randomised control study. Journal of Clinical Nursing 2015;25(5-6):664-71. [DOI: 10.1111/jocn.12988] - DOI - PubMed
Faulkner 2000 {published data only}
    1. Faulkner MA, Wadibia EC, Lucas BD, Hilleman DE. Impact of pharmacy counseling on compliance and effectiveness of combination lipid-lowering therapy in patients undergoing coronary artery revascularization: a randomized, controlled trial. Pharmacotherapy 2000;20(4):410-6. - PubMed
Fischer 2014 {published data only}
    1. Fischer MA, Choudhry NK, Bykov K, Brill G, Bopp G, Wurst AM, et al. Pharmacy-based interventions to reduce primary medication nonadherence to cardiovascular medications. Medical Care 2014;52(12):1050-4. - PubMed
Goswami 2013 {published data only}
    1. Goswami NJ, Dekoven M, Kuznik A, Mardekian J, Krukas MR, Liu LZ, et al. Impact of an integrated intervention program on atorvastatin adherence: a randomized controlled trial. International Journal of General Medicine 2013;6:647-55. [DOI: 10.2147/IJGM.S47518] - DOI - PMC - PubMed
Gujral 2014 {published data only}
    1. Gujral G, Winckel K, Nissen LM, Cottrell WN. Impact of community pharmacist intervention discussing patients’ beliefs to improve medication adherence. International Journal of Clinical Pharmacy 2014;36(5):1048-58. - PubMed
Guthrie 2001 {published data only}
    1. Guthrie RM. The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program. Clinical Therapeutics 2001;23(6):970-80. - PubMed
Ho 2014 {published data only}
    1. Ho PM, Lambert-Kerzner A, Carey EP, Fahdi IE, Bryson CL, Melnyk SD, et al. Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge: a randomized clinical trial. JAMA Internal Medicine 2014;174(2):186-93. - PubMed
Kardas 2013 {published data only}
    1. Kardas P. An education-behavioural intervention improves adherence to statins. Central European Journal of Medicine 2013;8(5):580-5.
Kooy 2013 {published data only}
    1. Kooy MJ, Van Wijk BL, Heerdink ER, De Boer A, Bouvy ML. Does the use of an electronic reminder device with or without counseling improve adherence to lipid-lowering treatment? The results of a randomized controlled trial. Frontiers in Pharmacology 2013;4:69. - PMC - PubMed
Ma 2010 {published data only}
    1. Ma YS, Ockene IS, Rosal MC, Merriam PA, Ockene JK, Gandhi PJ. Randomized trial of a pharmacist-delivered intervention for improving lipid-lowering medication adherence among patients with coronary heart disease. Cholesterol 2010;2010:383281. [DOI: 10.1155/2010/383281] - DOI - PMC - PubMed
Márquez 1998 {published data only}
    1. Márquez Contreras E, Casado Martínez JJ, López de Andrés M, Corés Prieto E, López Zamorano JM, Moreno García JP, et al. Therapeutic compliance in dyslipidemias. A trial of the efficacy of health education. Atencion Primaria 1998;22(2):79-84. - PubMed
Márquez 2004 {published data only}
    1. Márquez Contreras E, Casado Martínez JJ, Corchado Albalat Y, Chaves Gonzalez R, Grandio A, Losada Velasco C, et al. Efficacy of an intervention to improve therapy compliance in lipaemia cases. Atencion Primaria 2004;33(8):15. - PMC - PubMed
Márquez 2007 {published data only}
    1. Márquez Contreras E, Casado Martínez JJ, Motero Carrasco J, Martín de Pablos JL, Chaves Gonzales R, Losada Ruiz C, et al. Therapy compliance in cases of hyperlipaemia, as measured through electronic monitors. Is a reminder calendar to avoid forgetfulness effective? Atencion Primaria 2007;39(12):661-8. - PMC - PubMed
Nieuwkerk 2012 {published data only}
    1. Nieuwkerk PT, Nierman MC, Vissers MN, Locadia M, Greggers-Peusch P, Knape LPM, et al. Intervention to improve adherence to lipid-lowering medication and lipid-levels in patients with an increased cardiovascular risk. American Journal of Cardiology 2012;110(5):666-72. - PubMed
Park 2013 {published data only}
    1. Park LG, Howie-Esquivel J, Chung ML, Dracup K. A text messaging intervention to promote medication adherence for patients with coronary heart disease: A randomized controlled trial. Patient Education and Counseling 2013;94(2):261-8. - PubMed
Patel 2015 {published data only}
    1. Patel A, Cass A, Peiris D, Usherwood T, Brown A, Jan S, et al. A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk. European Journal of Preventive Cardiology 2015;22(7):920-30. - PubMed
PILL 2011 {published data only}
    1. PILL Collaborative Group. An international randomised placebo-controlled trial of a four-component combination pill (‘‘Polypill’’) in people with raised cardiovascular risk. PLOS One 2011;6(5):e19857. - PMC - PubMed
Pladevall 2014 {published data only}
    1. Pladevall M, Divine G, Wells KE, Resnicow K, Williams LK. A randomized controlled trial to provide adherence information and motivational interviewing to improve diabetes and lipid control. Diabetes Educator 2015;41(1):136-46. - PMC - PubMed
Poston 1998 {published data only}
    1. Poston J, Loh E, Dunham W. The medication use study. Canadian Pharmaceutical Journal 1998;131(10):31-8.
Powell 1995 {published data only}
    1. Powell KM, Edgren B. Failure of educational videotapes to improve medication compliance in a health maintenance organization. American Journal of Health-System Pharmacy 1995;52(20):2196-9. - PubMed
Schectman 1994 {published data only}
    1. Schectman G, Hiatt J, Hartz A. Telephone contacts do not improve adherence to niacin or bile acid sequestrant therapy. Annals of Pharmacotherapy 1994;28(1):29-35. - PubMed
Selak 2014 {published data only}
    1. Selak V, Elley CR, Bullen C, Crengle S, Wadham A, Rafter N, et al. Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care. BMJ 2014;348:g3318. - PubMed
Sweeney 1991 {published data only}
    1. Sweeney ME, Fletcher BJ, Rice CR, Berra KA, Rudd CM, Fletcher GF, et al. Efficacy and compliance with cholestyramine bar versus powder in the treatment of hyperlipidemia. American Journal of Medicine 1991;90(4):469-73. - PubMed
Tamblyn 2009 {published data only}
    1. Tamblyn R, Reidel K, Huang A, Taylor L, Winslade N, Bartlett G, et al. Increasing the detection and response to adherence problems with cardiovascular medication in primary care through computerized drug management systems: a randomized controlled trial. Medical Decision Making 2009;30(2):176-88. - PubMed
Thom 2013 {published data only}
    1. Thom S, Poulter N, Field J, Patel A, Prabhakaran D, Stanton A, et al. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD (UMPIRE). JAMA 2013;310(9):918-29. - PubMed
Vollmer 2014 {published data only}
    1. Vollmer WM, Owen-Smith AA, Tom JO, Laws R, Ditmer DG, Smith DH, et al. Improving adherence to cardiovascular disease medications with information technology. American Journal of Managed Care 2014;20(11 Spec No. 17):SP502-10. - PMC - PubMed
Vrijens 2006 {published data only}
    1. Vrijens B, Belmans A, Matthys K, De Klerke E, Lesaffre E. Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin. Pharmacoepidemiology and Drug Safety 2006;15(2):115-21. - PubMed
Wald 2014 {published data only}
    1. Wald DS, Bestwick JP, Raiman L, Brendell R, Wald NJ. Randomised trial of text messaging on adherence to cardiovascular preventive treatment (INTERACT Trial). PLoS ONE 2014;9(12):e114268. - PMC - PubMed
Willich 2009 {published data only}
    1. Willich SN, Englert H, Sonntag F, Voller H, Meyer-Sabellek W, Wegscheider K, et al. Impact of a compliance program on cholesterol control: results of the randomized ORBITAL study in 8108 patients treated with rosuvastatin. European Journal of Cardiovascular Prevention and Rehabilitation 2009;16(2):180-7. - PubMed

References to studies excluded from this review

Allen 2000 {published data only}
    1. Allen JK. Cholesterol management: an opportunity for nurse case managers. Journal of Cardiovascular Nursing 2000;14(2):50-8. - PubMed
Anon 2002 {published data only}
    1. Anonymous. Is alternate day dosing more cost-effective? Pharmaceutical Journal 2002;269(7224):706.
Athyros 2002b {published data only}
    1. Athyros VG, Mikhailidis DP, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, et al. Attaining United Kingdom-European Atherosclerosis Society low-density lipoprotein cholesterol guideline target values in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Current Medical Research and Opinion 2002;18(8):499-502. - PubMed
Becker 1998 {published data only}
    1. Becker DM, Raqueno JV, Yook RM, Kral BG, Blumenthal RS, Moy TF, et al. Nurse-mediated cholesterol management compared with enhanced primary care in siblings of individuals with premature coronary disease. Archives of Internal Medicine 1998;158(14):1533-9. - PubMed
Bogden 1997 {published data only}
    1. Bogden PE, Koontz LM, Williamson P, Abbott RD. The physician and pharmacist team. An effective approach to cholesterol reduction. Journal of General Internal Medicine 1997;12(3):158-64. [MEDLINE: ] - PMC - PubMed
Bruckert 1999 {published data only}
    1. Bruckert E, Simonetta C, Giral P. Compliance with fluvastatin treatment characterization of the noncompliant population within a population of 3845 patients with hyperlipidemia: CREOLE Study Team. Journal of Clinical Epidemiology 1999;52(6):589-94. - PubMed
Burkett 1990 {published data only}
    1. Burkett PA, Southard DR, Herbert WG, Walberg J. Frequent cholesterol feedback as an aid in lowering cholesterol levels. Journal of Cardiopulmonary Rehabilitation 1990;10(4):141-6. [EMBASE: 1990218703]
Casebeer 1999 {published data only}
    1. Casebeer LL, Klapow JC, Centor RM, Stafford MA, Renkl LA, Mallinger AP, et al. An intervention to increase physicians' use of adherence-enhancing strategies in managing hypercholesterolemic patients. Academic Medicine 1999;74(12):1334-9. - PubMed
Coates 1982 {published data only}
    1. Coates TJ, Jeffery RW, Slinkard LA. Frequency of contact and monetary reward in weight loss, lipid change, and blood pressure reduction with adolescents. Behavior Therapy 1982;13(2):175-85.
DeBusk 1994 {published data only}
    1. DeBusk RF, Miller NH, Superko HR, Dennis CA, Thomas RJ, Lew HT, et al. A case-management system for coronary risk factor modification after acute myocardial infarction. Annals of Internal Medicine 1994;120(9):721-9. - PubMed
Diabetes 2000 {published data only}
    1. Diabetes Prevention Program Research Group. The Diabetes Prevention Program: baseline characteristics of the randomized cohort. Diabetes Care 2000;23(11):1619-29. - PMC - PubMed
Diwan 1995 {published data only}
    1. Diwan VK, Wahlstrom R, Tomson G, Beermann B, Sterky G, Eriksson B. Effects of "group detailing" on the prescribing of lipid-lowering drugs: a randomized controlled trial in Swedish primary care. Journal of Clinical Epidemiology 1995;48(5):705-11. - PubMed
Dobs 1994 {published data only}
    1. Dobs AS, Masters RB, Rajaram L, Stillman FA, Wilder LB, Margolis S, et al. A comparison of education methods and their impact on behavioral change in patients with hyperlipidemia. Patient Education and Counseling 1994;24(2):157-64. - PubMed
Dunham 2000 {published data only}
    1. Dunham DM, Stewart RD, Laucka PV. Low-density-lipoprotein cholesterol in patients treated by a lipid clinic versus a primary care clinic. American Journal of Health-System Pharmacy 2000;57(24):2285-6. - PubMed
Ellis 2000 {published data only}
    1. Ellis SL, Carter BL, Malone DC, Billups SJ, Okano GJ, Valuck RJ, et al. Clinical and economic impact of ambulatory care clinical pharmacists in management of dyslipidemia in older adults: the IMPROVE study. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers. Pharmacotherapy 2000;20(12):1508-16. - PubMed
Eriksson 1998 {published data only}
    1. Eriksson M, Hadell K, Holme I, Walldius G, Kjellstrom T. Compliance with and efficacy of treatment with pravastatin and cholestyramine: a randomized study on lipid-lowering in primary care. Athereosclerosis 1997;134:55. - PubMed
    1. Eriksson M, Hadell K, Holme I, Walldius G, Kjellstrom T. Compliance with and efficacy of treatment with pravastatin and cholestyramine: A randomized study on lipid-lowering in primary care. Journal of Internal Medicine 1998;243(5):373-80. - PubMed
Frances 2001 {published data only}
    1. Frances CD, Alperin P, Adler JS, Grady D. Does a fixed physician reminder system improve the care of patients with coronary artery disease? A randomized controlled trial. Western Journal of Medicine 2001;175(3):165-6. - PMC - PubMed
Fretheim 2006 {published data only}
    1. Fretheim A, Oxman AD, Havelsrud K, Treweek S, Kristoffersen DT, Bjorndal A. Rational prescribing in primary care (RaPP): a cluster randomized trial of a tailored intervention. PLoS Medicine / Public Library of Science 2006;3(6):e134. - PMC - PubMed
Friedman 1998 {published data only}
    1. Friedman RH. Automated telephone conversations to assess health behavior and deliver behavioral interventions. Journal of Medical Systems 1998;22(2):95-102. - PubMed
Gaede 1999 {published data only}
    1. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999;353(9153):617-22. - PubMed
Gaede 2003 {published data only}
    1. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. New England Journal of Medicine 2003;348(5):383-93. - PubMed
Hae 2007 {published data only}
    1. Hae MC. Impact of patient financial incentives on participation and outcomes in a statin pill-splitting program. American Journal of Managed Care 2007;13(6):298-304. - PubMed
Ives 1993 {published data only}
    1. Ives DG, Kuller LH, Traven ND. Use and outcomes of a cholesterol-lowering intervention for rural elderly subjects. American Journal of Preventive Medicine 1993;9(5):274-81. [MEDLINE: ] - PubMed
Jafari 2003 {published data only}
    1. Jafari M, Ebrahimi R, Ahmadi-Kashani M, Balian H, Bashir M. Efficacy of alternate-day dosing versus daily dosing of atorvastatin. Journal of Cardiovascular Pharmacology and Therapeutics 2003;8(2):123-6. - PubMed
Jiang 2007 {published data only}
    1. Jiang X, Sit JW, Wong TK. A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu, China. Journal of Clinical Nursing 2007;16(10):1886-97. - PubMed
Johannesson 1996 {published data only}
    1. Johannesson M, Borgquist L, Jonsson B, Lindholm LH. The cost effectiveness of lipid lowering in Swedish primary health care. The CELL Study Group. Journal of Internal Medicine 1996;240(1):23-9. - PubMed
Jolly 1998 {published data only}
    1. Jolly K, Bradley F, Sharp S, Smith H, Mant D. Follow-up care in general practice of patients with myocardial infarction or angina pectoris: initial results of the SHIP trial. Southampton Heart Integrated Care Project. Family Practice 1998;15(6):548-55. [MEDLINE: ] - PubMed
Keyserling 1997 {published data only}
    1. Keyserling TC, Ammerman AS, Davis CE, Mok MC, Garrett J, Simpson R Jr. A randomized controlled trial of a physician-directed treatment program for low-income patients with high blood cholesterol: the Southeast Cholesterol Project. Archives of Family Medicine 1997;6(2):135-45. [MEDLINE: ] - PubMed
Kirkman 1994 {published data only}
    1. Kirkman MS, Weinberger M, Landsman PB, Samsa GP, Shortliffe EA, Simel DL, et al. A telephone-delivered intervention for patients with NIDDM. Effect on coronary risk factors. Diabetes Care 1994;17(8):840-6. [MEDLINE: ] - PubMed
Kjelsberg 1990 {published data only}
    1. Kjelsberg MO. Mortality after 10 1/2 years for hypertensive participants in the multiple risk factor intervention trial. Circulation 1990;82(5):1616-28. - PubMed
Kulik 2013 {published data only}
    1. Kulik A, Desai NR, Shrank WH, Antman EM, Glynn RJ, Levin R, et al. Full prescription coverage versus usual prescription coverage after coronary artery bypass graft surgery: analysis from the post-myocardial infarction free Rx event and economic evaluation (FREEE) randomized trial. Circulation 2013;128(Suppl 1):S219-S225. - PubMed
Kuznar 2002 {published data only}
    1. Kuznar W. Protocol helps drug adherence. Cardiology Review 2002;19(3):6.
Lee 2007 {published data only}
    1. Lee JK. How should we measure medication adherence in clinical trials and practice? Therapeutics and Clinical Risk Management 2007;3(4):2007. - PMC - PubMed
Lesaffre 2000 {published data only}
    1. Lesaffre E, De Klerk E. Estimating the power of compliance - Improving methods. Controlled Clinical Trials 2000;21(6):540-51. - PubMed
Lin 2006 {published data only}
    1. Lin EH, Katon W, Rutter C, Simon GE, Ludman EJ, Von Korff M, et al. Effects of enhanced depression treatment on diabetes self-care. Annals of Family Medicine 2006;4(1):46-53. - PMC - PubMed
Lindholm 1996 {published data only}
    1. Lindholm LH, Ekbom T, Dash C, Isacsson A, Schersten B. Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study. Journal of Internal Medicine 1996;240(1):13-22. - PubMed
Merriam 1997 {published data only}
    1. Merriam PA, Ockene IS, Hebert JR, Ma Y. A lipid trial tracking system. Journal of Public Health Management and Practice 1997;3(6):74-8. - PubMed
Moher 2001 {published data only}
    1. Moher M, Yudkin P, Wright L, Turner R, Fuller A, Schofield T, et al. Cluster randomised controlled trial to compare three methods of promoting secondary prevention of coronary heart disease in primary care. BMJ 2001;322(7298):1338-42. - PMC - PubMed
Oi 1998 {published data only}
    1. Oi K, Komori H. Escape phenomenon with pravastatin during long-term treatment of patients with hyperlipidemia associated with diabetes mellitus. Current Therapeutic Research, Clinical and Experimental 1998;59(2):130-8.
Oosterhoff 2011 {published data only}
    1. Oosterhof P, Van Boven JF, Visser ST, Hiddink EG, Stuurman-Bieze AG, Postma MJ, et al. Cost effectiveness of increasing statin adherence for secondary prevention in community pharmacies. Value in Health 2011;14:A379.
Polack 2008 {published data only}
    1. Polack J, Jorgenson D, Robertson P. Evaluation of different methods of providing medication-related education to patients following myocardial infarction. Canadian Pharmacists Journal / Revue des Pharmaciens du Canada 2008;141:241.
Rachmani 2002 {published data only}
    1. Rachmani R, Levi Z, Slavachevski I, Avin M, Ravid M. Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus: a randomized prospective study. Diabetic Medicine 2002;19(5):385-92. - PubMed
Rastam 1996 {published data only}
    1. Rastam L, Frick J-O. Nurses counseling for hypercholesterolemia: Efficient strategy in middle-aged men. Cardiovascular Risk Factors 1996;6(1):36-41.
Rindone 1998 {published data only}
    1. Rindone JP, Hiller D, Arriola G. A comparison of fluvastatin 40 mg every other day versus 20 mg every day in patients with hypercholesterolemia. Pharmacotherapy 1998;18(4):836-9. [MEDLINE: ] - PubMed
Robin 2002 {published data only}
    1. Robin DM, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Medical Care 2002;40(9):794-811. - PubMed
Rodgers 2000 {published data only}
    1. Rodgers J. Pharmacological interventions in type 2 diabetes: the role of nurses. British Journal of Nursing 2000;9(13):866-70. - PubMed
Rubenfire 2004 {published data only}
    1. Rubenfire M, Impact of Medical Subspecialty on Patient Compliance to Treatment Study Group. Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. American Journal of Cardiology 2004;94(3):306-11. - PubMed
Schectman 1996 {published data only}
    1. Schectman G, Wolff N, Byrd JC, Hiatt JG, Hartz A. Physician extenders for cost-effective management of hypercholesterolemia. Journal of General Internal Medicine 1996;11(5):277-86. [MEDLINE: ] - PubMed
Scherwitz 1995 {published data only}
    1. Scherwitz LW, Brusis OA, Kesten D, Safian PA, Hasper E, Berg A, et al. Life style changes in patients with myocardial infarct in the framework of intramural and ambulatory rehabilitation--results of a German pilot study [Lebensstilanderung bei Herzinfarktpatienten im Rahmen der stationaren und ambulanten Rehabilitation--Ergebnisse einer deutschen Pilotstudie]. Zeitschrift fur Kardiologie 1995;84(3):216-21. - PubMed
Shaffer 1995 {published data only}
    1. Shaffer JW. Reducing low-density lipoprotein cholesterol levels in an ambulatory care system. Results of a multidisciplinary collaborative practice lipid clinic compared with traditional physician-based care. Archives of Internal Medicine 1995;155(21):2330-5. - PubMed
Simpson 2001 {published data only}
    1. Simpson SH, Johnson JA, Tsuyuki RT. Economic impact of community pharmacist intervention in cholesterol risk management: an evaluation of the study of cardiovascular risk intervention by pharmacists. Pharmacotherapy 2001;21(5):627-35. - PubMed
Toobert 2000 {published data only}
    1. Toobert DJ, Glasgow RE, Radcliffe JL. Physiologic and related behavioral outcomes from the women's lifestyle heart trial. Annals of Behavioural Medicine 2000;22(1):1-16. - PubMed
Tsuyuki 1999 {published data only}
    1. Tsuyuki RT, Johnson JA, Teo KK, Ackman ML, Biggs RS, Cave A, et al. Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP): a randomized trial design of the effect of a community pharmacist intervention program on serum cholesterol risk. Annals of Pharmacotherapy 1999;33(9):910-9. - PubMed
Tully 2000 {published data only}
    1. Tully MP, Seston EM. Impact of pharmacists providing a prescription review and monitoring service in ambulatory care or community practice. Annals of Pharmacotherapy 2000;34(11):1320-31. - PubMed
Vale 2002 {published data only}
    1. Vale MJ, Jelinek MV, Best JD, Santamaria JD. Coaching patients with coronary heart disease to achieve the target cholesterol: a method to bridge the gap between evidence-based medicine and the "real world"--randomized controlled trial. Journal of Clinical Epidemiology 2002;55(3):245-52. - PubMed
Wahlstrom 1995 {published data only}
    1. Wahlstrom R, Tomson G, Diwan VK, Beermann B, Sterky G. Hyperlipidaemia in primary care - a randomized controlled trial on treatment information in Sweden: Design and methodology. Pharmacoepidemiology and Drug Safety 1995;4(2):75-90.
Weymiller 2007 {published data only}
    1. Weymiller AJ. Helping patients with type 2 diabetes mellitus make treatment decisions: Statin choice randomized trial. Archives of Internal Medicine 2007;167(10):28. - PubMed
Wright 2002 {published data only}
    1. Wright L. The specialist nurse in coronary heart disease prevention: Evidence for effectiveness. British Journal of Cardiology 2002;9 Suppl 3:S15-9.
Wu 2006 {published data only}
    1. Wu JY, Leung WY, Chang S, Lee B, Zee B, Tong PCY, et al. Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: Randomised controlled trial. BMJ 2006;333(7567):522-7. - PMC - PubMed
Yigit 2004 {published data only}
    1. Yigit F, Muderrisoglu H, Guz G, Bozbas H, Korkmaz ME, Ozin MB, et al. Comparison of intermittent with continuous simvastatin treatment in hypercholesterolemic patients with end stage renal failure. Japanese Heart Journal 2004;45(6):959-68. - PubMed
Yilmaz 2005 {published data only}
    1. Yilmaz MB, Pinar M, Naharci I, Demirkan B, Baysan O, Yokusoglu M, et al. Being well-informed about statin is associated with continuous adherence and reaching targets. Cardiovascular Drugs and Therapy 2005;19(6):437-40. - PubMed
Zermansky 2002 {published data only}
    1. Zermansky AG, Petty DR, Raynor DK, Lowe CJ, Freemantle N, Vail A. Clinical medication review by a pharmacist of patients on repeat prescriptions in general practice: A randomised controlled trial. Health Technology Assessment 2002;6(20):76. - PubMed

References to studies awaiting assessment

Harrison 2015 {published data only}
    1. Harrison TN, Green KR, Liu IA, Vansomphone SS, Handler J, Scott RD, et al. Automated outreach for cardiovascular-related medication refill reminders. Journal of Clinical Hypertension 2015;18(7):641-6. [DOI: 10.1111/jch.12723] - DOI - PMC - PubMed
    1. Reynolds K, Green KR, Vansomphone SS, Scott RD, Cheetham TC. Automated outreach for cholesterol-lowering medication refill reminders. European Heart Journal 2011;32(Abstract Suppl):230-1.
Johnson 2006 {published data only}
    1. Johnson SS, Driskell MM, Johnson JL, Dyment SJ, Prochaska JO, Prochaska JM, et al. Transtheoretical model intervention for adherence to lipid-lowering drugs. Disease Management 2006;9(2):102-14. - PubMed
Lee 2006 {published data only}
    1. Lee JK. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA 2006;296(21):2563-71. - PubMed

References to ongoing studies

ACTRN12616000233426 {published data only}
    1. ACTRN12616000233426. INtegrated combination Therapy, Electronic General practice support tool, phaRmacy led intervention And combination Therapy Evaluation (INTEGRATE): A pragmatic cluster randomised controlled trial. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370068 19th February 2016.
ACTRN12616000422426 {published data only}
    1. ACTRN12616000422426. Text4Heart Partnership: a text messaging program to enhance self-management of cardiovascular disease. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370398 1st April 2016.
Thom 2014 {published data only}
    1. Thom S, Field J, Poulter N, Patel A, Prabhakaran D, Stanton A, et al. Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe. European Journal of Preventive Cardiology 2014;21:252-61. - PubMed

Additional references

4S 1994
    1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344(8934):1383-9. - PubMed
ACC/AHA Guidelines 2013
    1. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in AdultsA Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):s1-45. - PubMed
Armour 2007
    1. Armour C, Bosnic-Anticevich S, Brilliant M, Burton D, Emmerton L, Krass I, et al. Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community. Thorax 2007;62:496-592. - PMC - PubMed
Athyros 2002a
    1. Athyros VG, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, Basayannis EO, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Current Medical Research and Opinion 2002;18(4):220-8. - PubMed
Avorn 1998
    1. Avorn J, Monette J, Lacour A, Bohn RL, Monane M, Mogun H, et al. Persistence of use of lipid-lowering medications. JAMA 1998;279(18):1458-62. - PubMed
Baigent 2005
    1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al, 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):1267-78. - PubMed
Benner 2002
    1. 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. - PubMed
Blackburn 2005
    1. Blackburn DF, Dobson RT, Blackburn JL, Wilson TW. Cardiovascular morbidity associated with nonadherence to statin therapy. Pharmacotherapy 2005;25(8):1035-43. - PubMed
Brown 2011
    1. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clinic Proceedings 2011;86(4):304-14. - PMC - PubMed
Cheng 2004
    1. Cheng CW, Woo K-S, Chan JC, Tomlinson B, You JH. Association between adherence to statin therapy and lipid control in Hong Kong Chinese patients at high risk of coronary heart disease. British Journal of Clinical Pharmacology 2004;58(5):528-35. - PMC - PubMed
Costa 2015
    1. Costa E, Giardini A, Savin M, Menditto E, Lehane E, Laosa O, et al. Interventional tools to improve medication adherence: review of literature. Patient Preference and Adherence 2015;9:1303–14. - PMC - PubMed
Dickersin 1994
    1. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964):1286-91. - PMC - PubMed
Downs 1998
    1. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279(20):1615-22. - PubMed
Ebrahim 1998
    1. Ebrahim S. Detection, adherence and control of hypertension for the prevention of stroke: a systematic review. Health Technology Assessment 1998;2(11):1-78. [www.hta.ac.uk/project.asp?PjtId=881] - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Handbook of Systemtic Reviess of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Jackevicius 2002
    1. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288(4):462-7. - PubMed
Lefebvre 1996
    1. Lefebvre C, McDonald S. Development of a sensitive search strategy for reports of randomized controlled trials in EMBASE. In: Paper presented at the Fourth International Cochrane Colloquium, 20-24 Oct 1996; Adelaide, Australia. 1996.
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Lewis 2003
    1. Lewis DK, Robinson J, Wilkinson E. Factors involved in deciding to start preventive treatment: qualitative study of clinicians' and lay people's attitudes. BMJ 2003;327(7419):841-5. - PMC - PubMed
LIPID 1998
    1. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. New England Journal of Medicine 1998;339(19):1349-57. - PubMed
Mahtani 2011
    1. Mahtani KR, Heneghan CJ, Glasziou PP, Perera R. Reminder packaging for improving adherence to self-administered long-term medications. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No: CD005025. [DOI: 10.1002/14651858.CD005025.pub3] - DOI - PubMed
Marinker 1997
    1. Marinker M. From Compliance to Concordance: Towards Shared Goals in Medicine taking. London: Royal Pharmaceutical Society of Great Britain, 1997.
MRC/BHF 2002
    1. Heart Protection Study Collaborative Group. MRC/BHF Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360(9326):7-22. - PubMed
Mullen 1997
    1. Mullen PD. Compliance becomes concordance. BMJ 1997;314(7082):691-2. - PMC - PubMed
Muller‐Nordhorn 2005
    1. Muller-Nordhorn J, Willich SN. Effectiveness of interventions to increase adherence to statin therapy. Disease Management of Health Outcomes 2005;13(2):72-82. [1173-8790/05/0002-0073/$34.95/0]
NICE 2014
    1. National Institute for Health and Care Excellence (NICE). Cardiovascular Disease: risk assessment and reduction, including lipid modification. www.nice.org.uk/guidance/cg181 (accessed 18th December 2016). - PubMed
Nieuwlaat 2014
    1. Nieuwlaat R, Wilczynksi N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, et al. Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No: CD000011. [DOI: 10.1002/14651858.CD000011.pub4] - DOI - PMC - PubMed
Pasina 2014
    1. Pasina L, Brucato AL, Falcone C, Cucchi E, Bresciani A, Sottocorno M, et al. Medication non-adherence among elderly patients newly discharged and receiving polypharmacy. Drugs & Aging 2014;31(4):283–9. [DOI: 10.1007/s40266-014-0163-7] - DOI - PubMed
Primatesta 2000
    1. Primatesta P, Poulter NR. Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross sectional survey. BMJ 2000;321(7272):1322-5. - PMC - PubMed
Rash 2016
    1. Rash JA, Campbell DJ, Tonelli M, Campbell TS. A systematic review of interventions to improve adherence to statin medication: what do we know about what works? Preventive Medicine 2016;90:155-69. [DOI: 10.1016/j.ypmed.2016.07.006] - DOI - PubMed
Rosenson 2015
    1. Rosenson R, Kent ST, Brown TM, Farkouh ME, Levitan EB, Yun H, et al. Underutilization of high-intensity statin therapy after hospitalization for coronary heart disease. Journal of the American College of Cardiology 2015;65(3):270-7. - PubMed
Rueda 2006
    1. Rueda S, Park-Wyllie LY, Bayoumi A, Tynan A-M, Antoniou T, Rourke S, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No: CD001442. [DOI: 10.1002/14651858.CD001442.pub2] - DOI - PMC - PubMed
Sackett 1976
    1. Sackett DL, Haynes RB. Compliance with Therapeutic Regimens. Baltimore: John Hopkins University Press, 1976.
Sacks 1996
    1. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. New England Journal of Medicine 1996;335(14):1001-9. - PubMed
Schroeder 2004
    1. Schroeder K, Fahey T, Ebrahim S. Interventions for improving adherence to treatment in patients with high blood pressure in ambulatory settings. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No: CD004804. [DOI: 10.1002/14651858.CD004804] - DOI - PMC - PubMed
Shepherd 1995
    1. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. New England Journal of Medicine 1995;333(20):1301-07. - PubMed
SIGN 2007
    1. Scottish Intercollegiate Guidelines Network (SIGN). Risk estimation and the prevention of cardiovascular disease. A national clinical guideline.. Available at www.sign.ac.uk/pdf/sign97.pdf 2007 (accessed 11th January 2009).
Tsuyuki 2001
    1. Tsuyuki RT, Bungard TJ. Poor adherence with hypolipidemic drugs: a lost opportunity. Pharmacotherapy 2001;21(5):576-82. - PubMed
Vermeire 2001
    1. Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient adherence to treatment: three decades of research. A comprehensive review. Journal of Clinical Pharmacy and Therapeutics 2001;26(5):331-42. - PubMed
Vermeire 2005
    1. Vermeire EIJJ, Wens J, Van Royen P, Biot Y, Hearnshaw H, Lindenmeyer A. Interventions for improving adherence to treatment recommendations in people with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No: CD003638. [DOI: 10.1002/14651858.CD003638.pub2] - DOI - PMC - PubMed
Wei 2002
    1. Wei L, Wang J, Thompson P, Wong S, Struthers AD, MacDonald TM. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart (British Cardiac Society) 2002;88(3):229-33. - PMC - PubMed
WHO Report 2002
    1. World Health Organization. The World Health Report 2002 - Reducing risks, promoting healthy life. Available at www.who.int/whr/2002/en/whr02_en.pdf?ua=1 2002 (accessed 18th December 2016).

References to other published versions of this review

Schedlbauer 2003
    1. Schedlbauer A, Schroeder K. Interventions to improve adherence to lipid lowering medication. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No: CD004371. [DOI: 10.1002/14651858.CD004371] - DOI - PMC - PubMed
Schedlbauer 2004
    1. Schedlbauer A, Schroeder K, Peters TJ, Fahey T. Interventions for improving adherence to lipid lowering medication. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No: CD004371. [DOI: 10.1002/14651858.CD004371.pub2] - DOI - PMC - PubMed
Schedlbauer 2010
    1. Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No: CD004371. [DOI: 10.1002/14651858.CD004371.pub3] - DOI - PubMed

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