Table 1.
Patient characteristics, intervention types (based on the categorization used in Fig. 2) and the methods and raw data for all adherence, persistence and cholesterol measures used in each study
| Ref # | Author Study design |
Statin treatment indication and/or status (country) | N | Mean age (y)a | Female, % | Follow-up (mo.) | Intervention | Adherence measure: intervention vs. control (significance)b | Cholesterol measure: intervention vs. control (significance)b | |
|---|---|---|---|---|---|---|---|---|---|---|
| Implementationc | Persistenced | |||||||||
| [20] | Yilmaz et al. (2005) RCT |
Secondary CVD prevention (Turkey) | Int: 102 Con: 100 |
53 ± 8 54 ± 10 |
46 49 |
15 | 1A(S) | Proportion taking statins continuously: 62.7 vs. 46.0 % (p = 0.017) | Proportion still taking statins: 86.3 vs. 64.0 % (p < 0.001) | Proportion reaching LDL-C target of <100 mg/dL: 64.7 vs. 43.0 % (p = 0.002) |
| [21] | Faulkner et al. (2000) RCT |
Secondary CVD prevention (USA) | Int: 15 Con: 15 |
64 ± 12 61 ± 12 |
47 40 |
24 | 1B(M) (int only) 1A(S) (int and con) |
Proportion taking ≥80 % of pills based on pill counts: 63 vs. 39 % (p < 0.05) | NA | Mean change in LDL-C (mg/dL): −24.3 vs. −14.9 (p = 0.02) |
| [22] | Alsabbagh et al. (2012) RCT |
Secondary CVD prevention; statin-naïve (Canada) | Int: 46 Con: 48 |
20.4 ± 10.5 63.5 ± 11.9 |
20 23 |
10 | 1B(S) | Mean MPR: 0.87 vs. 0.90 (p = 0.058) | Mean number of days between first and last refill: 381.2 vs. 403.0 (p = 0.39) | NA |
| [23] | Charland et al. (2014) Prospective; Matched controls |
Statin naïve (USA) | Int: 647 Con: 647 |
60 ± 12 59 ± 11 |
54 56 |
6 | 1C (KIF6 genotype and associated treatment recommendation) | Mean PDC: 0.77 vs. 0.68 (p < 0.0001) Proportion with PDC ≥0.80: 63.4 vs. 45.0 % (p < 0.001) |
Proportion still taking statins: 69.1 vs. 53.3 % (p < 0.0001) | NA |
| [24] | Li et al. (2014) Prospective; Un-matched controls; Statistical analysis adjusted for patient characteristics that were significantly different between the intervention and control group |
Non-adherent to statins (USA) | Int: 58 Con: 59 |
63.6 ± 9 63.6 ± 13.3 |
64 76 |
12 | 1E (SLCO1B1*5 genotype via website) | Proportion self-reporting adherence at 12 mo.: 47 vs. 15 % (p < 0.001) | Proportion receiving new statin prescriptions by 4 mo.: 55 vs. 20 % (p < 0.001) | Mean change in LDL-C (mg/dL): −12.4 vs. 6.3 (p = 0.059) |
| [25] | Peng et al. (2014) Cluster RCT 47 hospitals randomized to intervention or control group |
Secondary CVD prevention (China) | Int: 1795 Con: 2026 |
61.5 ± 11.5 60.4 ± 11.7 |
33 31 |
12 | 1E (unique password-protected website) | Proportion of adherent patients (not defined): 56 vs. 33 % (p = 0.006) | NA | NA |
| [26] | Pringle et al. (2014) Patients were own controls |
Non-adherent to statins (USA) | Int: 29,042 Con: 30,454 |
59 60 |
57 55 |
12 | 2A(M) | Mean PDC: 0.66 (before int) vs. 0.73 (after int) (p < 0.001) Change from baseline in proportion with PDC ≥0.80: 7 vs. 2 % (p < 0.001) |
NA | NA |
| [27] | Taitel et al. (2012) Retrospective; Unmatched controls; Statistical analysis adjusted for co-variates |
Statin naïve (USA) | Int: 586 Con: 516 |
54.2 ± 12.4 56.0 ± 12.2 |
54 51 |
12 | 2A(M) | Mean MPR: 0.62 vs. 0.57 (p < 0.01) Proportion with MPR ≥0.80: 40.9 vs. 33.7 % (p < 0.01) |
Proportion persistent (<60 consecutive days without any statin medication available): 43.9 vs. 38.2 % (p = 0.05) | NA |
| [28] | Thiebaud et al. (2008) Prospective; Matched controls |
Diabetes (USA) | Int: 2598 Con: 2598 |
52.8 51.1 |
78 70 |
12 | 2B(M) | Mean MPR: 0.56 vs. 0.55 (p = 0.65) Proportion with MPR ≥0.80: 32.7 vs. 30.4 % (p = 0.23) |
NA | NA |
| [29] | Johnson et al. (2006) RCT |
LLDs, not exclusively statins (USA) | Int: 202 Con: 202 |
Range: 21–85 y | 50 50 |
18 | 2C(M) | Mean Medication Adherence Scale (MAS) questionnaire score (higher score = better adherence): 3.4 vs. 3.0 (p < 0.01) | NA | NA |
| [30] | Foreman et al. (2012) Retrospective; Matched-controls |
(USA) | Int: 290 Con: 290 |
64.8 ± 11.9 64.7 ± 13.7 |
47 54 |
8 | 4 | Mean PDC: 0.82 vs. 0.79 (p = 0.49) | NA | NA |
| [31] | Kooy et al. (2013) RCT |
Non-adherent to statins (Netherlands) | Int 1: 123 Int 2: 130 Con: 128 |
73.2 ± 5.8 73.3 ± 6.6 73.9 ± 6.5 |
57 53 58 |
12 | 4 (int 1 and int 2) 1A(S) (int 2) 5 (int 2) |
Proportion with PDC ≥0.80 for int 1 vs. con: 72.4 vs. 64.8 % (p = 0.18) Proportion with PDC ≥0.80 for int 2 vs. con: 69.2 vs. 64.8 % (p = 0.55) |
Proportion who discontinued for int 1 vs. con: 5.7 vs. 9.4 % (p = 0.37) Proportion who discontinued for int 2 vs. con: 6.2 vs. 9.4 % (p = 0.37) |
NA |
| [32] | Pladevall et al. (2014) RCT |
Diabetes (HbA1c and LDL-C not at goal); LLDs, ~80 % taking statins (USA) | Int 1: 569 Int 2: 556 Con: 567 |
63.3 ± 10.9 64.5 ± 10.5 64.9 ± 11.5 |
47 48 53 |
6 | 5 (int 1 and int 2) 2A or B(M) (int 2) |
Mean MPR for int 1 vs. con: 0.70 vs. 0.70 (p = 0.952) Mean MPR for int 2 vs. con: 0.70 vs. 0.70 (p = 0.856) |
NA | Mean LDL-C (mg/dL) for int 1 vs. con: 87.3 vs. 89.0 (p = 0.38) Mean LDL-C (mg/dL) for int 2 vs. con: 85.6 vs. 86.0 (p = 0.08) |
| [33] | Wu et al. (2012) RCT |
Secondary CVD prevention (China) | Int: 55 Con: 55 |
73.2 ± 7.2 75.7 ± 6.4 |
22 18 |
12 | 1A(M) 1C(S) |
Proportion of patients who were compliant (not defined): 94.6 vs. 32.7 % (p = 0.016) | NA | NA |
| [34] | Nieuwkerk et al. (2012) RCT |
50 % primary CVD prevention; 50 % secondary CVD prevention; statin naïve (Netherlands) | Int: 100 Con: 101 |
48.9 ± 1.2 49.2 ± 1.3 |
41 40 |
18 | 1A(M) 1E (risk-factor passport) |
Mean score based on number of days patients reported taking their medication in the past week (1 = no days; 5 = all 7 days): 4.9 vs. 4.6 (p < 0.01) Mean score based on proportion of medication patients reported taking in the past month (1 = < 30 %; 10 = 100 %): 9.4 vs. 8.9 (p < 0.05) |
NA | Mean LDL-C (mg/dL) in primary prevention patients: 103 vs. 116 (p < 0.05) Mean LDL-C (mg/dL) in secondary prevention patients: 97 vs. 92 (p = NS) |
| [35] | Kardas et al. (2013) RCT |
Primary hypercholesterolemia (Poland) | Int: 107 Con: 89 |
59.5 ± 8.8 59.7 ± 9.5 |
75 76 |
11 | 1A(M) 2A(M) |
Mean MPR: 0.95 vs. 0.82 (p < 0.05) | Mean persistence (wks): 36.1 vs. 35.5 (p = NS) | NA |
| [36] | Ali et al. (2003) Patients were own controls |
High CVD risk (age and ≥2 two other risk factors [e.g. smoking, diabetes]); non-adherent to LLDs (Canada) | Int: 135 (own controls) | Men aged >45 y Women aged >55 y |
NR | 6 | 1A(S) (int only) 1B(M) (int only) 1A(S) (int and con) 1C(S) (int and con) |
Mean days between refills: 38 vs. 49 (p < 0.001) Proportion renewing prescription within 6 days of 30-day renewal date: 56.0 % vs 40.7 % (p < 0.05) |
NA | Mean LDL-C (mmol/L): 2.91 vs. 3.18 (p < 0.01) Proportion reaching LDL-C target of <3.4 mmol/L: 82.7 vs. 72.7 % (p < 0.05) Proportion reaching LDL-C target of <2.6 mmol/L: 35.5 vs. 28.2 % (p = NS) |
| [37] | Guthrie et al. (2001) RCT |
High CVD risk (score ≥4 on First Heart Attack Risk Test); statin naïve (USA) | Int: 10,355 Con: 2765 |
57.9 58.3 |
51 52 |
6 | 1B(M) (int only) 1C(S) (int only) 1A(S) (int and con) 1C(M) (int and con) |
Proportion self-reporting adherence: 79.7 vs. 77.4 % (p = NS) | NA | NA |
| [38] | Stuurman-Bieze et al. (2013) Prospective; Unmatched historical control group; Statistical analysis adjusted for confounders |
Non-adherent to LLDs, 98 % taking statins (Netherlands) | Int: 502 Con: 500 |
61.3 ± 11.2 60.9 ± 11.7 |
45 42 |
12 | 1F(M) (int only) 2F(M) (int only) 1A(M) (int and con) 1C(S) (int and con) |
Proportion who discontinued or were non-adherent (MPR ≤0.80): 16.8 vs. 33.5 % (p < 0.001) | Proportion who discontinued: 13.6 vs. 25.9 % (p < 0.001) | NA |
| [39] | Brath et al. (2013) RCT |
High CVD risk (≥2 of following: diabetes, high cholesterol and hypertension) (Austria) | Int: 53 (own controls) | 69.4 ± 4.8 | 45 | 13 | 4 5 |
Definition of adherence unclear (p = 0.23) | NA | Median LDL-C (mg/dL): 80 vs. 87 (p = 0.06) |
| [40] | Lee et al. (2004) Prospective; Patients assigned to intervention or control group based on appointment date |
Hyperlipidemia; statin naive (Hong Kong) | Int: 26 Con: 24 |
49.2 ± 8.7 50.9 ± 10.8 |
19 17 |
3 | 1A(M) 1B(S) 1C(S) |
Mean proportion of doses taken (assessed by direct questioning of patients): 82.1 vs. 60.5 % (p < 0.05) Proportion taking ≥75 % of doses (assessed by direct questioning of patients): 76.9 vs. 41.7 % (p < 0.01) |
NA | Mean change in LDL-C (mg/dL): –27.7 vs. –16.3 (p < 0.05) |
| [41] | Eussen et al. (2010) RCT |
Statin naïve (Netherlands) | Int: 513 Con: 503 |
60.2 ± 10.9 60.1 ± 11.3 |
53 50 |
12 | 1A(M) 1C(S) 1E (treatment goal wallet card) |
Median MPR: 1.0 vs. 0.99 (p = 0.14) | Proportion who discontinued within 6 months of initiation: 11 vs. 16 % (p = 0.03) Proportion who discontinued within 12 months of initiation: 23 vs. 26 % (p = 0.21) |
NA |
| [42] | Vrijens et al. (2006) RCT |
(Belgium) | Int: 194 Con: 198 |
61.9 ± 9.9 60.4 ± 10.2 |
45 54 |
12 | 1A(M) 4 5 |
Median proportion of days taking statins (assessed by MEMS): 95.9 vs. 89.4 % (p < 0.001) | Proportion persistent (still taking statin after 300 days): 87 vs. 74 % (p = 0.002) | NA |
| [43] | Casebeer et al. (2009) Prospective; Matched controls |
Statin naïve (USA) | Int: 355 Con: 196 |
58 | NR | 4 | 1A(S) 1C(M) 2E (contract/pledge to confirm commitment to taking statins) |
Mean MPR: 0.68 vs. 0.57 (p < 0.01) | Proportion persistent (still refilling statin prescriptions): 67.8 vs. 57.8 % (p < 0.01) | NA |
| [44] | Hedagaard et al. 2014 RCT |
Secondary CVD prevention (Denmark) | Int: 90 Con: 87 |
64 (range: 56–73) 68 (range: 61–73) |
40 38 |
12 | 2A(S) 2B(M) 2C(M) |
Median MPR: 1.0 vs. 0.98 (p = 0.68) Proportion with MPR <0.80: 22 vs. 21 % (p = 0.86) |
Proportion non-persistent (prescription not redeemed <90 days after last prescription ran out): 20 vs. 18 % (p = NS) | NA |
| [45] | Ma et al. (2010) RCT |
Secondary CVD prevention (USA) | Int: 351 Con: 338 |
60.4 ± 10.5 60.3 ± 10.4 |
40 40 |
12 | 1A(S) 1C(S) 2B(M) 2E (medication card) 2E (pillbox) |
Mean adherence (total days of supply divided by total days between refills): 0.90 vs. 0.88 (p = 0.51) | NA | Mean LDL-C (mg/dL): 94.5 vs. 97.8 (p = 0.24) Proportion reaching LDL-C target of <100 mg/dL: 64.5 vs. 60.2 % (p = 0.29) Proportion reaching LDL-C target of <70 mg/dL: 17.1 vs. 18.8 % (p = 0.66) |
| [46] | Calvert et al. (2012) RCT |
Secondary CVD prevention (USA) | Int: 51 Con: 50 |
63 (range: 54–71) 62 (range: 52–70) |
34 39 |
6 | 1A(S) 2C(S) 2E (medication card) 2E (adherence tip sheet) |
Proportion with PDC ≥0.75: 58 vs. 49 % (p = 0.34) Proportion self-reporting adherence: 98 vs. 98 % (p = 0.99) |
NA | NA |
| [47] | Stacy et al. (2009) RCT |
Statin naïve (USA) | Int: 253 Con: 244 |
54.6 54.2 |
62 63 |
6 | 1C(S) 1D(M) 1E (website) 2C(S) 2D(M) |
Proportion with MPR ≥0.80: 47.0 vs. 38.9 % (p < 0.1; considered statistically significant in this study) | Proportion of patients still in possession of a statin: 70.4 vs. 60.7 % (p < 0.05) | NA |
| [48] | Ho et al. (2014) RCT |
Secondary CVD prevention (USA) | Int: 122 Con: 119 |
63.8 ± 9.3 64.0 ± 8.57 |
2 3 |
12 | 1A(M) 1B(optional) 1D(M) 2E (pillbox) 3 4 |
Mean PDC: 0.95 vs. 0.84: (p < 0.001) Proportion with PDC ≥0.80: 93.2 vs. 71.3 % (p < 0.001) |
Mean LDL-C (mg/dL): 80 vs. 76 (p = 0.37) Mean reduction in LDL-C (mg/dL): –13 vs. –12 (p = 0.9) Proportion reaching LDL-C target of <100 mg/dL: 72 vs. 83 % (p = 0.14) |
|
| [49] | Goswami et al. (2013) RCT |
(USA) | Int: 375 Con: 125 |
69.5 ± 12.3 67.8 ± 10.6 |
41 32 |
6 | 1C (optional) 2A(S) 2C(S) 2E (co-pay relief card-optional) |
Mean PDC: 0.82 vs. 0.81 (p = NS) Mean MPR: 0.82 vs. 0.79 (p = NS) Proportion with PDC ≥0.80: 71.6 vs 71.7 % (p = NS) Proportion with MPR ≥0.80: 76.8 vs. 75.5 % (p = NS) |
Mean persistence (days): 147.4 vs. 146.3 (p = NS) | NA |
| [50] | Holdford and Inocencio (2013) Prospective; Matched controls |
Taking statins and ≥1 other medication type (USA) | Int: 1281 Con: 18,361 |
68.4 ± 14.1 | 100 | 12 | 3 2E(optional) |
Mean PDC: 0.84 vs. 0.62 (p < 0.0001) Proportion with PDC ≥0.80: 76.2 vs 37.4 % (p < 0.0001) |
Proportion non-persistent (not taking medication for ≥30 consecutive days): 41.6 vs. 72.5 % (p < 0.0001) | NA |
| [51] | Evans et al. (2010) RCT |
High CVD risk (10-year Framingham risk score of ≥15%) (Canada) | Int: 88 Con: 88 |
60.2 ± 10.2 60.3 ± 10.1 |
17 22 |
6 | 1A, B, C or E (e-mail) (M) (int only) 1A(S) (int and con) 1C(S) (int and con) |
Proportion with PDC ≥0.80: 73.1 vs. 80.0 % (p = 0.33) | Median LDL-C (mg/dL): 90.2 vs. 90.5 (p = 0.99) | |
1 cognitive education; 2 behavioural counselling; 3 treatment simplification; 4 medication reminders; 5 adherence feedback; A face-to-face; B telephone (person); C hard copy materials; D telephone (automated); E other delivery method; S single time; M multiple times; int intervention group; con control group
CVD cardiovascular disease, LDL-C low-density lipoprotein cholesterol, LLDs lipid lowering drugs, MEMS Medication Event Monitoring System, MPR medication possession ratio, PDC proportion of days covered, NA not applicable, NR not reported
aMean ± standard deviation or standard error unless otherwise specified
bData are for intervention versus control unless otherwise specified
cDefined as any data on the extent to which the patients actual dosing corresponds to the prescribed dosing regimen [19]
dDefined as any data on the length of time between treatment initiation and the last dose [19]