Table 1.
Summary of Clinical Trials, by Intervention Type
| Study Reference | Country | Study Design | Study Duration | Sample Size | Intervention Details | Comparison Group | Adherence Measure | Outcome |
|---|---|---|---|---|---|---|---|---|
| Patient Education | ||||||||
| Aghakhani et al, [46] | Iran | RCTa | 4 weeks | 60 | Blended education consisting of face-to-face education and online education via emails | Traditional face-to face education | Novel self-report questionnaire | 46.7% of intervention group reported good medication adherence vs. 0% of control group at 4 weeks. (P < .001) |
| Delavar et al, [28] | Iran | RCT | 1 month | 118 | Health literacy tailored self-management education utilizing teach back method and delivered face-to-face and by telephone | Usual care | MMAS-8 | 50% of participants in the intervention groups reported moderate or good medication adherence vs 21% of the control group at 1 month (P=0.002) |
| Yazdanpanah et al, [29] | Iran | RCT | 1 month | 60 | Community-based educational sessions based on Health Belief Model | Usual Care | MMAS-8 | Mean MMAS change was higher in the intervention group (2.6 ±0.8) vs the control group score (−0.1±0.1) at 1 month (P<0.001) |
| Harvin et al [18] | USA | Pre-post test | 4 months | 10 | Faith-based self-management education program guided by the Understanding and Controlling Your High Blood Pressure booklet | N/A | HTN Self-Care Activity Level Effects Scale (H-scale) |
There was a 30% increase in the number of participants who reported being adherent to their antihypertensive medications at 4 months (P=0.034) |
| Simplification of Medication Regimen | ||||||||
| Doshi et al [55] | USA | Retrospective cohort study | 12 months | 11,452 | Synchronized refill schedule of all maintenance drugs | Non-synchronized refills | PDCc | Adherence was higher in the intervention group (92%) vs control group (86%) at 12 months (P<0.01) |
| Verma et al, [54] | Canada | Retrospective cohort study | 5 years | 13,350 | Fixed Dose Combination (FDC) pill | Multiple-pill combination (MPC) | PDC Time to 1st Discontinuation |
Adherence was higher in the intervention group (70%) vs control group (42%) at 5 years (P< 0.01); Time to 1st discontinuation was 41 days longer in the intervention group vs control group (P< 0.01) |
| Kim et al, [53] | Korea | Retrospective cohort study | 5 years | 116,677 | Single Pill Combination (SPC) | MPC Angiotensin Receptor Blocker (ARB)-only Calcium Channel Blocker (CCB)-only |
MPRd | Adjusted MPR was higher in combination therapy (89.7% in SPC, 87.2% in MPC) than monotherapy (81.6% in ARB, 79.7% in CCB), and MPR of SPC (89.7%, 95% CI 89.3 to 90.0) was higher than MPR of MPC (87.2%, 95% CI 86.7 to 87.7) (p<0.05). |
| Shen et al, [30••] | China | RCT | 6 months | 518 | Low-cost reminder package (28 compartment pill box w/alarm) combined with two case-based health education session | Usual care | Novel self-report questionnaire | Mean scores were higher in the intervention group vs the control group with a difference in change of (0.287; [0.103, 0.471] P=0.002) |
| Fleig et al, [52] | Germany | Prospective cohort study | 12 weeks | 1814 | FDC pill | MPC | Hill-Bone Medication Adherence scale | In previously treated patients, adherence increased from 20.6% to 43.4% (P<0.0001) |
| Ho et al, [51] | Taiwan | Retrospective cohort study | 12 months | 17,568 | FDC pill | MPC | PDC | FDC pill was associated with better medication adherence (58%) vs than MPC (47%) at 12 months (P <0.001) |
| Tan et al, [58] | Malaysia | RCT | 7 months | 73 | Calendar blister packaging | Normal blister packaging | MPR Percentage of on-time refills |
Mean MPR for the interventions group was 0.99 and 0.98 for the control group (P=0.012); percentage of on-time refills was 0.99 for the intervention and 0.93 for the control (P=0.001) |
| Bartlett et al, [50] | Australia | Retrospective cohort study | 12 months | 26,848 | Fixed-dose Combination pill | Separate pill combination (SePC) | Cessation of combination therapy (persistence) | Cessation rates at 12 months were lower in in the SePC group (40%) vs FDC (44%); following adjustment for differences in age, safety-net and prior antihypertensive, the risk of cessation was higher in those that initiated the SePC: hazard ratio (95%CI)-1.15 (1.11, 1.21) |
| Electronic Health Tool | ||||||||
| Zare et al [59] | Iran | Matched control | 8 weeks | 120 | Smartphone app with educational self-care information and BP monitoring 2x/week combined with case management | Usual care | Hill-Bone hypertension self-care questionnaire | Mean adherence scores were higher in the intervention group (4.21) vs the control group (3.09) at 8 weeks (P ⩽0.001) |
| Morawski et al, [14] | USA | RCT | 12 weeks | 411 | Smartphone app with reminder alerts, adherence reports, and optional peer support | Usual care | MMAS-8 | Mean MMAS scores were higher in the intervention group (6.3) vs the control group score (5.7) at 12 weeks; Mean MMAS change scores were higher in the intervention group (0.4) vs the control group score (−0.1) at 12 weeks (P<0.01) |
| Sarfo et al, [32••] | Ghana | RCT | 9 months | 60 | Smartphone app with Bluetooth enabled BP device for home BP monitoring (HBPM) and reporting medications; and motivational text messages based upon levels of adherence | SMS messages about healthy lifestyle behaviors but not medication adherence | MPR MMAS-8 |
MPR was higher in the intervention group (0.88) than the control group (0.64) at 3 months (P=0.03); however, this difference was not sustained as MPR for the intervention group (0.95) than the control group (0.98) at 9 months (P=0.56); MMAS-8 was 13 in both groups (P=0.94) |
| Marquez Contreras et al, [33] | Spain | RCT | 12 months | 154 | Smartphone app with reminder alarms, BP measurement records and recommended BP levels, doctor’s advice about the prescribed treatment and posology; and calendar of appointments or events | Usual care | Global adherence via Medication Event Monitoring Systems (MEMS), defined as percentage between ≥80% of all doses taken | Global adherence was higher in the intervention group (93%) vs the control group (75%) at 6 months (P<0.01). Adherence decreased in the control group to 63% at 12 months whereas the intervention group stayed relatively consistent (92%) (P<0.01) |
| Varleta et al, [34] | Chile | RCT | 6 months | 314 | SMS text messages related to medication adherence and healthy lifestyle practices | Usual care | MMAS-4 | Mean adherence scores were higher in the intervention group vs the control group at 6 months (62.3% vs. 51.4%, P<0.01) |
| Buis et al, [35] | USA | RCT | 1 month | 123 | Daily medication reminders and two educational text messages per week based upon the Health Belief Model | Usual care | MMAS-8 | Intervention group had greater mean change on the MMAS (0.9) compared to the control group (0.5) ( P=.26) |
| Chandler et al, [36] | USA | RCT | 9 months | 54 | Smartphone app with a Bluetooth enabled BP monitor for HBPM, as well as an electronic medication and reminder text messages | Text messages with links to PDFs and video clips with lifestyle tips | MMAS-8 Medication tray time-stamped data |
Mean adherence scores were higher in the intervention group (9.81) vs the control group (6.84) at 9 months with a change in difference of 2.971 (P<0.001) |
| Moorhead et al, [56] | USA | Post hoc analysis | 12 weeks | 57 | Co-encapsulated, ingestible, sensor-enabled medication with dose reminder within 30 minutes of the scheduled dose | Usual care | Mean daily adherence and mean difference in proportion of medications taken after seeing and not seeing the dose reminder | Reminder messages were associated with a 16 ± 16% increase in medication adherence; impact was larger on patients who have lower overall adherence (<60%) |
| Persell et al, [21] | USA | RCT | 6 months | 333 | Conversational smartphone app using artificial intelligence and cognitive behavioral therapy to coach and promote HBPM and lifestyle behavior changes | Blood pressure tracking app plus HBPM | 4-day recall | The percentage of participants with full adherence was 80.6% in the intervention group and 81.7% in the control group at 6 months (P=0.99) |
| Behavioral Counseling Strategies | ||||||||
| Abughosh et al, [22] | USA | RCT | 6 months | 743 | Pharmacy-led telephone motivational interviewing using Ask-Provide-Ask approach | Usual Care | PDC (adherence = PDC ≥ 0.80) Discontinuation |
Patients receiving 2 or more calls were more likely to become adherent (OR: 1.53; P = 0.009) and less likely to discontinue (OR: 0.29; P < 0.001) during the 6 months following initial calls compared with those who did not receive calls |
| Bolarinwa et al, [23] | Nigeria | RCT | 6 months | 299 | Nurse-led health education and counseling on healthy lifestyle behaviors and medication adherence delivered in the home | Usual care | MMAS-8 Low= <6 Medium= 6-7.99 High= 8 |
Percentage of participants with high medication adherence was higher in the intervention group (78.5%) vs control group (48.7%) at 6 months. (P<0.001) |
| van der Laan et al, [25] | Netherlands | RCT | 9 months | 170 | Two pharmacist-led consultations to identify participants’ barriers to medication adherence and counseling to overcome these barriers. | Usual care | MARS-5 | No significant between group differences in the total sample. A significant intervention effect was found in participants with ≥ 3 barriers identified during the first consultation at 9 months (mean difference 0.84 [95CI: 0.03 to 1.65], p = 0.04) |
| Sheilini et al, [24] | India | RCT | 6 months | 160 | Nurse-led individualized education; medication reminder boxes; and reminder calls | Usual care | MMAS-8 | Mean adherence scores were higher in the intervention group (8.00) vs the control group (7.70) at 6 months (F(1.75,214.30)=4.24, p=0.02) |
| Mirniam et al, [26] | Iran | RCT | 4 weeks | 72 | Nurse-led motivational interviewing and educational sessions, use of a medication reminder box, family support, and weekly phone calls with patient and family | Usual care plus a medication reminder box and educational training booklet | MMAS-8 | Mean change in MMAS score was higher in the intervention group (2.91 ± 1.64) than the control group (−0.36) at 4 week (P < 0.001) |
| Amer et al, [27] | Pakistan | RCT | 3 months | 384 | Face-to-face pharmacist-led educational session and interview addressing adherence, lifestyle choices, and barriers | Usual care | MMAS | Mean MMAS scores were higher in the intervention group (5.89 ± 1.90) vs the control group (3.89 ± 1.19) at 3 months (P<0.001) |
| Kim et al, 2019 [38] | Korea | RCT | 2 months | 124 | Face-to-face nurse-led health coaching 30 minutes once a week. Tailored text messages delivered up to two times a day Combination intervention of face-to-face nurse-led health coaching and tailored text messages |
Usual Care | MMAS | Mean MMAS score was significantly higher in the combination group (2.87 ± 1.11), as compared to face-to-face health coaching (2.503 ± 1.22), text-message delivered health coaching (1.87 ± 1.38), and usual care (0.87 ± 1.08) at 2 months (P<0.001) |
| Joshi et al, [37] | India | RCT | 12 months | 1164 | CHW-delivered advice on reduction of risk factors with household visits every 2 months | Usual Care | Proportion of consumed to prescribed number of pills | Adherence to antihypertensive drugs was greater in the intervention (74.9%) vs control households (61.4%) at 12 months (P=0.001) |
| Financial Incentives | ||||||||
| Yeung et al, [57] | USA | Interrupted time series | 3 years | 3436 | Value-based formulary that used cost-effectiveness analysis to inform medication co-payments. | Similar plans without any changes in pharmacy benefits | PDC | No between group differences in medication adherence (P=.279). Member expenditures decreased ($4 per member per month (PMPM); P <.001), health plan expenditures increased ($5 PMPM; P <.001). |
| Kim et al, [49] | Korea | Retrospective cohort study | 12 months | 3908 | Multilevel chronic disease management program including copayment reduction and physician incentives | Usual care | MPR: (0.8–1.1) Persistence: 12-month cumulative persistence rate |
Pre-post change in MPR adherence improved +6.0% (P <0.001) and 12-month cumulative persistence improved +6.5% (P <0.001). |
| Tamblyn et al, [39] | Canada | RCT | 12 months | 3592 | Decision support tool to help providers select the most cost-effective drug, as well as tools to monitor blood pressure (BP) targets and medication compliance | Medical record system with no out-of-pocket expenditure module | PDC | Mean adherence was higher in the intervention group for both incident (intervention 57.7%; control 52.8%; P=0.70) and prevalent patients (intervention 72.1%; control 70.7%; P=0.36) |
| Healthcare System Changes | ||||||||
| Schoenthaler et al, [40] | USA | RCT | 6 months | 119 | Systems-level intervention that used the electronic health record to identify patients with uncontrolled hypertension and refer them to Medical Assistant-led health coaching based on motivational interviewing | Standard health coaching (provision of patient education) | EMDe MMAS |
EMD-measured adherence declined in both groups; mean change in EMD adherence rates in the intervention group was −9.6% vs control group −6.6% at 6 months (p=0.66) Mean change in MMAS scores was higher in the intervention group (1.98) vs control group (1.26) at 6 months (p=0.03) |
| McWilliams et al, [48] | USA | Retrospective cohort study | 12 months | 2,169, 845 | Accountable care organization contracts/Medicare Shared Savings Program | Non- Medicare Shared Savings Program | PDC | No significant differential changes in PDC among beneficiaries with at least 1 prescription fill, except for slight increase in the PDC for β-blockers in the 2012 entry (adjusted differential change, 0.3 percentage point; 95% CI, 0.1-0.5 percentage points; or 0.4% of the mean PDC [82.3%]; P = .003) |
| Lauffen-burger et al, [47] | USA | Retrospective cohort study | 12 months | 4660 | Providers caring for patients using the patient-centered medical home (PCMH) model | Non-PCMH primary care practices | PDC | Medication adherence was higher in PCMH than non-PCMH practices (mean difference: 3.2% [95CI: 2.2% to 4.2%]) at 12 months |
| Son et al, [60••] | Korea | Non-equivalent control group design | 12 months | 2685 | Adoption of chronic care model in primary care practices including a community-based chronic disease management program | Usual care | Dispensation per prescription (DPP) Dispensation days per patient (DDPP) |
DPP and the DDPP in the intervention region increased by approximately 11% and 2.2 days on average by month, respectively, compared to those in the control region |
| Persell et al, [20] | USA | RCT | 12 months | 794 | EHR medication management tool (medication review sheets at check-in, lay medication information sheets printed after visits) with and without a nurse-led education intervention | Usual care | 4-Day Recall | Compared with usual care, the EHR tools alone and EHR plus education interventions did not improve medication adherence (OR, 0.9; 95%CI,0.6-1.4 for both) |
| Chronic Disease Management Program | ||||||||
| Shen et al, [41] | China | RCT | 12 months | 554 | Family based care management with educational text messages and medication reminders | Usual Care | Novel self-report questionnaire | Better adherence in the intervention group vs control group at 6 months (OR 3.82; P<0.001); however, this was not sustained at 12 months (OR 1.74; P=0.097) |
| Ozpancar et al, [42] | Turkey | RCT | 6 months | 60 | Case Management Model that included a hypertension care protocol, dietician and individualized hypertension education | Usual care | Scale for Adherence to Antihypertensive Medications (SAAM) | Mean scores were lower in the intervention group (i.e., better adherence, 3.77±1.19) vs the control group score (5.80±2.43) at 12 6 months; (P<0.001) |
| Mattei da Silva et al, [44] | Brazil | RCT | 12 months | 94 | Nurse case management model with individual care plans, tailored health education, home visits, and telephone calls for re-evaluations and reminders every 2 months | Usual care with free medications, HBPM and access to extended healthcare team (e.g., Nurse, dietician) | Questionnaire on Adherence to Treatment of Systemic Hypertension | No between group differences in medication adherence at 12 months; slight increase in medication adherence within the intervention group with absolute difference in treatment adherence as 4.8 [3.1; 6.4] (P<.001) vs the control group −1.1 [−2.9; 0.6] (P=0.206) |
| Home Blood Pressure Monitoring (HBPM) | ||||||||
| Muhammad et al, [43] | Malaysia | RCT | 2 months | 88 | HBPM with instructions to take daily readings and reminder phone call made at 1 month | Usual care | Novel self-report questionnaire: Mean Adherence Survey (MAS) | No significant between group difference in the intervention and control groups at 2 months (1.5 (0.9–2.1) vs 1.3 (0.6–1.9), P=0.77) |
| Cuffee et al, [45] | USA | RCT | 3 months | 213 | Home blood pressure monitor and 5 educational pamphlets from NHLBI Home blood pressure monitor and computer-based education modules |
Usual Care + 5 educational pamphlets Usual care + computer-based education modules |
MMAS-4 | No significant difference between intervention group mean change in score −0.18 (−0.45, 0.09) and the control group mean change in score −0.53 (−0.78, −0.28) (P = 0.068) |