Summary of findings of studies examining the associations of barriers/facilitators and adherence/persistence
| Barriers/facilitators | Study (author, year, setting) | Context | Study design | Sample size | Study details | Outcome | Relevant findings (95% CIs given where available and in italics when p<0.05) |
|---|---|---|---|---|---|---|---|
| Patient counselling | O'Carroll, 2013 (UK)21 | First stroke/TIA | RCT | 62 | Intervention=physician-led counselling sessions aimed at increasing adherence | Adherence 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)22 | Acute stroke/TIA | RCT | 349 | Intervention=four home visits by a nurse with individually tailored counselling on a healthy lifestyle | Adherence to antihypertensive therapy at 1 year Self-report | Intervention versus control: 98% vs 99%, OR 0.88, 95% CI 0.54 to 1.44; p=0.50 | |
| Maron, 2010 (USA and Canada)39 | Stable CHD | Prospective cohort | 2287 | Nurse-led case management nested in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial. CVD drugs provided at no cost | Adherence and persistence to 4D at 5 years Self-report | 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)23 | Stroke in hospital | RCT | 102 | Intervention=3 months nurse-led health counselling with written and verbal information on lifestyle, and check of medication concordance | Adherence and persistence to 4D at 3 years Self-report | 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)17 | CABG | RCT | 30 | Intervention=weekly pharmacist-led telephone contact for 12 weeks | Adherence 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)29 | Ischaemic stroke/TIA in hospital | Non-randomised, controlled intervention trial | 255 | Intervention=hospital pharmacist counselling before discharge and plan for outpatient care plus counselling by community pharmacists | Persistence 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)36 | ACS in hospital | Prospective cohort | 660 | 3 months after discharge for ACS, consecutive patients were invited to join a comprehensive risk factor management programme | Persistence to 4D at 20 months (mean follow-up) Self-report | 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)24 | Secondary prevention in hospital | RCT | 202 | Intervention=counselling regarding efficacy, pharmacokinetic profile, and side effects of ongoing statins | Persistence to statin therapy at 15 months (median follow-up) Self-report | 62.7% vs 46%; OR=1.98, 1.13 to 3.47; p=0.017 | |
| Hospital quality improvement programmes | Bushnell, 2011 (USA)30 | Ischaemic stroke/TIA in hospital | Retrospective cohort | 2457 | Guideline implementation in the Adherence eValuation After Ischemic stroke–Longitudinal (AVAIL) Registry in a sample of hospitals participating in the Get With The Guidelines—Stroke program | Persistence and adherence to 4D at 1 year Self-report | 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)31 | AMI in hospital | Retrospective cohort | 4591 | Quality improvement of care in the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study registry in Ontario | Adherence 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)19 | Ischaemic stroke in hospital | RCT | 3361 | Intervention: assistance in the development and implementation of standardised stroke discharge orders | Adherence 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)40 | CABG in hospital | Retrospective case–control | 403 | A physician education protocol to implement statin in all patients admitted for CABG | Persistence to statins at 6 months Self-report | Intervention versus control: 67% vs 58%, OR 1.49, 0.88 to 2.55; p=0.14 | |
| Site of care and home circumstances of patients | Glader, 2010 (Sweden)32 | Acute stroke in hospital | Prospective cohort | 21 077 | A 1-year cohort (September 2005–August 2006) from the Swedish Stroke Register | Persistence 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 drugs | O'Brien, 2015 (USA)37 | NSTEMI in hospital | Retrospective cohort | 1421 | NSTEMI patients ≥65 years old discharged on a statin in 2006 from USA hospitals | Adherence 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 regimen | Castellano, 2014 (Argentina, Brazil, Italy, Paraguay and Spain)25 | Aged >40 years with AMI in last 2 years | Cross-sectional study | 2118 | In a single visit, data was gathered to estimate prescription, adherence and barriers to adherence for aspirin, ACEIs, β blockers and statins | Adherence to 4D Self-report | 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) |
| FDC | Thom, 2013 (India, Europe)20 | High CV risk | RCT | 1698 | Intervention=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 Self-report | FDC versus separate medications: RR 1.29, 95% CI 1.22 to 1.36; p<0.0001 |
| FDC | Castellano, 2014 (Argentina, Brazil, Italy, Paraguay and Spain)25 | Aged >40 years with AMI within last 2 years. | RCT | 695 | Intervention=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)28 | High CV risk | RCT | 233 | Intervention=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 Self-report | FDC versus separate medications: RR 1.50, 95% CI 1.25 to 1.82; p<0001 | |
| Patel, 2015 (Australia, New Zealand)26 | High CV risk | RCT | 381 | Intervention=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) Self-report | FDC versus separate medications: RR 1.26, 95% CI 1.08 to 1.48; p<0001 | |
| Physician education/training | Ko, 2005 (Canada)18 | AMI aged ≥65 years in hospital | Retrospective cohort | 63 301 | Evaluation 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)33 | CHD in hospital | Cross-sectional and prospective Cohort | 2994 | Brief educational sessions with physicians to review National guidelines to ascertain physician's awareness | Persistence to statins at 8 weeks Self-report | Intervention versus control: 57% vs 45%. (p<0.001) | |
| Copayments for medical care | Winkelmayer, 2007 (Austria)34 | AMI in hospital | Retrospective cohort | 4105 | The association between copayments and outpatient use of β blockers, statins, and ACEI/ARB in Austrian MI patients | Adherence 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)35 | CHD and hospital-initiated statin | Retrospective cohort | 5548 | Databases containing inpatient admission, outpatient, enrollment and pharmacy claims from 1999 to 2003 to study associations with copayments | Adherence 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 assistance | Choudhry, 2011 (USA)27 | AMI in hospital | RCT | 5855 | Intervention=full prescription coverage by insurance-plan sponsor | Adherence 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)38 | ACS in hospital | Prospective cohort | 7955 | Within the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study | Persistence to 4D at 6 months Self-report | 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.