Table 2

Summary of findings of studies examining the associations of barriers/facilitators and adherence/persistence

Barriers/facilitatorsStudy (author, year, setting)ContextStudy designSample sizeStudy detailsOutcomeRelevant findings (95% CIs given where available and in italics when p<0.05)
Patient counsellingO'Carroll, 2013 (UK)21First stroke/TIARCT62Intervention=physician-led counselling sessions aimed at increasing adherenceAdherence to antihypertensive medication at 3 months
Electronic pill count and self-report
Intervention versus control: by electronic pill count, percentage of doses taken on schedule—96.8% vs 87.4%, mean difference 9.8%, 95% CI 0.2 to 16.2; p=0.048
Self-report highly correlated with electronic pill count
Hornnes, 2011 (Denmark)22Acute stroke/TIARCT349Intervention=four home visits by a nurse with individually tailored counselling on a healthy lifestyleAdherence to antihypertensive therapy at 1 year
Intervention versus control: 98% vs 99%, OR 0.88, 95% CI 0.54 to 1.44; p=0.50
Maron, 2010 (USA and Canada)39Stable CHDProspective cohort2287Nurse-led case management nested in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial. CVD drugs provided at no costAdherence and persistence to 4D at 5 years
Persistence increased from baseline to 5 years as follows: antiplatelets 87% to 96%, (OR 3.58, 95% CI 2.48 to 5.18); β blockers 69% to 85% (OR 2.54, 2.06 to 3.15); ARBs 46% to 72% (OR 3.02, 2.53 to 3.60), statins 64% to 93% (OR 7.51, 5.67 to 9.94), 4D 28% to 53% (OR 2.90, 95% CI 2.44 to 3.43) (all p<0.001).
Adherence was 97% at 6 months and 95% at 5 years
McManus, 2009 (UK)23Stroke in hospitalRCT102Intervention=3 months nurse-led health counselling with written and verbal information on lifestyle, and check of medication concordanceAdherence and persistence to 4D at 3 years
Persistence: 95% vs 89%, OR 3.00, 0.57 to 15.7 (p=0.19) for antiplatelets
97% vs 95%, OR 1.02, 0.55 to 1.91 (p=0.95) for antihypertensives
88% vs 89%, OR 1.03, 0.25 to 4.14 (p=0.97) for statins
Adherence to 4D: 78% vs 92%, OR 0.30, 0.07 to 1.24 (p=0.10)
Faulkner, 2000 (USA)17CABGRCT30Intervention=weekly pharmacist-led telephone contact for 12 weeksAdherence to lovastatin at 1 year and 2 years
Prescription fill rate
Intervention versus control: 67% vs 33%; p<0.05 at 1 year and 60% vs 27%; p<0.05 at 2 years (χ2 test reported)
At 1 year, OR 4.00, 0.88 to 18.26; p=0.07, and at 2 years, OR 4.13, 0.88 to 19.27; p=0.07
Hohmann, 2009 (Germany)29Ischaemic stroke/TIA in hospitalNon-randomised, controlled intervention trial255Intervention=hospital pharmacist counselling before discharge and plan for outpatient care plus counselling by community pharmacistsPersistence to aspirin and clopidogrel at 1 year
Self-reported and GP-reported
Intervention: 38.7% vs 32.7%, OR 1.30, 0.73 to 2.31; p=0.37 for aspirin and 26.7% and 30.1%, OR 0.85, 0.46 to 1.57; p=0.60 for clopidogrel
Lafitte, 2009 (France)36ACS in hospitalProspective cohort6603 months after discharge for ACS, consecutive patients were invited to join a comprehensive risk factor management programmePersistence to 4D at 20 months (mean follow-up)
At follow-up and baseline, respectively (no control group reported): 86% vs 98% for β blocker or a calcium antagonist, 88% vs 94% for statin, 96% vs 100% for antiplatelet, 62% vs 82% for ACEI/ARB, 76% vs 92% for 4D
Yilmaz, 2005 (Turkey)24Secondary prevention in hospitalRCT202Intervention=counselling regarding efficacy, pharmacokinetic profile, and side effects of ongoing statinsPersistence to statin therapy at 15 months (median follow-up)
62.7% vs 46%; OR=1.98, 1.13 to 3.47; p=0.017
Hospital quality improvement programmesBushnell, 2011 (USA)30Ischaemic stroke/TIA in hospitalRetrospective cohort2457Guideline implementation in the Adherence eValuation After Ischemic stroke–Longitudinal (AVAIL) Registry in a sample of hospitals participating in the Get With The Guidelines—Stroke programPersistence and adherence to 4D at 1 year
Persistence and adherence associated with: number of medications prescribed at discharge (OR=1.08, 1.04 to 1.11; p<0.001 per 1 decrease); and follow-up appointment with GP (OR=1.72, 1.12 to 2.52; p=.0.006)
Jackevicius, 2008 (Canada)31AMI in hospitalRetrospective cohort4591Quality improvement of care in the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study registry in OntarioAdherence to 4D at 120 days
Prescription fill rate
Predischarge medication counselling: OR 1.61, 1.26 to 2.04; p=0.0001
Cardiologist (vs GP) as doctor responsible for patient's care: OR 1.80, 1.34 to 2.43; p=0.0001. Teaching versus other hospital: OR 1.35,0.93 to 1.97; p=0.11
Johnston, 2010 (USA)19Ischaemic stroke in hospitalRCT3361Intervention: assistance in the development and implementation of standardised stroke discharge ordersAdherence to statin at 6 months
Prescription fill rate
Intervention versus non-intervention hospitals,
At hospital level: OR, 1.26; 0.70 to 2.30; p=0.36.
At individual level: OR, 1.29; 1.04 to 1.60; p=0.02
Khanderia, 2005 (USA)40CABG in hospitalRetrospective case–control403A physician education protocol to implement statin in all patients admitted for CABGPersistence to statins at 6 months
Intervention versus control: 67% vs 58%, OR 1.49, 0.88 to 2.55; p=0.14
Site of care and home circumstances of patientsGlader, 2010 (Sweden)32Acute stroke in hospitalProspective cohort21 077A 1-year cohort (September 2005–August 2006) from the Swedish Stroke RegisterPersistence with 4D at 1 year
Prescription fill rate
Institutional living correlated with persistence for all drug classes (p=0.001). Stroke unit care was associated with persistence for statins (p=0.007).
Support by next-of-kin associated with persistence for antihypertensives (p=0.001)
Generic versus branded drugsO'Brien, 2015 (USA)37NSTEMI in hospitalRetrospective cohort1421NSTEMI patients ≥65 years old discharged on a statin in 2006 from USA hospitalsAdherence to statins at 1 year
Prescription refill rate
Generic versus brand users: 86.0% (IQR=42.6–97.2%) vs 84.1% (IQR=53.4–97.0%)), (p=0.97)
Complexity of treatment regimenCastellano, 2014 (Argentina, Brazil, Italy, Paraguay and Spain)25Aged >40 years with AMI in last 2 yearsCross-sectional study2118In a single visit, data was gathered to estimate prescription, adherence and barriers to adherence for aspirin, ACEIs, β blockers and statinsAdherence to 4D
Non-adherence was associated with age <50 years (OR 1.50, 95% CI 1.08 to 2.09; p=0.015), depression (OR 1.07, 95% CI 1.04 to 1.09; p<0.001), being on a complex medication regimen (OR 1.42, 95% CI 1.00 to 2.02: p=0.047) and lower level of social support (OR 0.94 0.92 to 0.96; p<0.001)
FDCThom, 2013 (India, Europe)20High CV riskRCT1698Intervention=FDC (containing either: 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide)Adherence to 4D at 15 months
FDC versus separate medications: RR 1.29, 95% CI 1.22 to 1.36; p<0.0001
FDCCastellano, 2014 (Argentina, Brazil, Italy, Paraguay and Spain)25Aged >40 years with AMI within last 2 years.RCT695Intervention=FDC (containing aspirin 100 mg, simvastatin 40 mg and ramipril 2.5, 5 or 10 mg)Adherence at 9 months
Self-report and pill count
FDC versus separate medications: RR 1.24, 95% CI 1.06 to 1.47; p=0.009
Selak, 2014 (New Zealand)28High CV riskRCT233Intervention=FDC (with two versions available: aspirin 75 mg, simvastatin 40 mg and lisinopril 10 mg with either atenolol 50 mg or hydrochlorothiazide 12.5 mg)Adherence to 4D at 12 months
FDC versus separate medications: RR 1.50, 95% CI 1.25 to 1.82; p<0001
Patel, 2015 (Australia, New Zealand)26High CV riskRCT381Intervention=FDC (containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg)Adherence to 4D at 18 months (median follow-up)
FDC versus separate medications: RR 1.26, 95% CI 1.08 to 1.48; p<0001
Physician education/trainingKo, 2005 (Canada)18AMI aged ≥65 years in hospitalRetrospective cohort63 301Evaluation on whether care by International medical graduates (IMGs) is a determinant of poor persistence and worse outcomes after AMI versus care by Canadian medical graduates (CMGs)Persistence to 4D at 90 days
Prescription refill
Adjusted OR(Canadian/IMG): aspirin 1.00 95% CI (0.94 to 1.06); BB 1.01 (0.94 to 1.08); ACEI 1.07 (1.01 to 1.14); statins 1.10 (1.01 to 1.20)
Harats, 2005 (Israel)33CHD in hospitalCross-sectional and prospective Cohort2994Brief educational sessions with physicians to review National guidelines to ascertain physician's awarenessPersistence to statins at 8 weeks
Intervention versus control: 57% vs 45%. (p<0.001)
Copayments for medical careWinkelmayer, 2007 (Austria)34AMI in hospitalRetrospective cohort4105The association between copayments and outpatient use of β blockers, statins, and ACEI/ARB in Austrian MI patientsAdherence at 120 days
Prescription refill rate
Adherence (waived copayments versus copayment): OR 1.35; 95% CI 1.10 to 1.67 for ACEI/ARB, OR 1.09; 0.89 to 1.35) for β blocker and OR 1.09;0.89 to 1.34 for statin
Ye, 2007 (USA)35CHD and hospital-initiated statinRetrospective cohort5548Databases containing inpatient admission, outpatient, enrollment and pharmacy claims from 1999 to 2003 to study associations with copaymentsAdherence to statins at 1 year
Prescription refill rate
Adherence (copayment US$20 vs copayment <US$10): OR 0.42; 95% CI 0.36 to 0.49
Insurance and prescription cost assistanceChoudhry, 2011 (USA)27AMI in hospitalRCT5855Intervention=full prescription coverage by insurance-plan sponsorAdherence to 4D at 394 days (median follow-up)
Prescription refill rate
Full-coverage versus usual coverage: OR 1.41, 95% CI 1.18 to 1.56; p<0.001 for 4D and p<001 for all individual drug classes
Mathews, 2015 (USA)38ACS in hospitalProspective cohort7955Within the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) studyPersistence to 4D at 6 months
Non-persistence less likely with private insurance (OR 0.85, 95% CI 0.76 to 0.95), prescription cost assistance (OR 0.63, 0.54 to 0.75), and clinic follow-up arranged predischarge (OR 0.89, 0.80 to 0.99)
  • 4D, secondary prevention drugs for CVD, namely, antiplatelets, β blockers, angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers and statins; ACEI, angiotensin-converting enzyme inhibitor; AMI, acute myocardial infarction; ACS, acute coronary syndrome; ARB, angiotensin-receptor blocker; CABG, coronary artery bypass graft; CHD, coronary heart disease; CVD, cardiovascular disease; FDC, fixed-dose combination therapy; GP, general practitioner; NSTEMI, non ST-elevation myocardial infarction; RCT, randomised controlled intervention trial; RR, relative risk; TIA, transient ischaemic attack.