TABLE 1.
Studies reporting assessments of adherence or persistence with single-pill combination therapy or with free-dose combination therapy
| 1st Author (year) [REF], study type | Sample size | Treatment (SPC/free) | Treatment details | Follow-up (months) | Measure of adherence /persistence | Adherent/persistent,a n (%) | P value |
| (a) Measures of adherenceb | |||||||
| Bramlage (2018) [22] – Obs | 10 938 | SPC | ram/amlo | 12 | MPR ≥ 80% | 5699 (52.1) | <0.001 |
| 60 525 | Free | ram + amlo | 12 | MPR ≥ 80% | 19 913 (32.9) | ||
| 1413 | SPC | cand/amlo | 12 | MPR ≥ 80% | 1195 (84.6) | <0.001 | |
| 9082 | Free | cand + amlo | 12 | MPR ≥ 80% | 5286 (58.2) | ||
| Webster (2018) [46] – RCT | 349 (321, adherence calculation) | SPC | tel/amlo/chlo | 6 | Ingestion ≥ 4 of last 7 days | 305 (95.0) | 0.82 |
| 351 (336, adherence calculation) | Free | Not specified | 6 | Ingestion ≥ 4 of last 7 days | 318 (94.6) | ||
| Degli Esposti (2018) [24] – Obs | 3597 | SPC | per/amlo | 12 | PDC ≥ 80% | 2597 (72.2) | NR |
| 20 423 | Free | Not specified | 12 | PDC ≥ 80% | 12 969 (63.5) | ||
| Lauffenburger (2017) [31] – Obs | 79 958 | SPC | Not specified | 12 | PDC ≥ 80% | 40 505 (51.3) | NR |
| 383 269 | Mono | Not specified | 12 | PDC ≥ 80% | 161 356 (42.1) | ||
| Levi (2016) [32] – Obs | 4522 | SPC | olm/amlo | 6 | PDC ≥ 80% | 1684 (55.1) | <0.001 |
| 2090 | Free | olm + amlo | 6 | PDC ≥ 80% | 291 (15.9) | ||
| Machnicki (2015) [34] – Obs | 1884 | SPC | amlo/val/HCTZ | 12 | PDC ≥ 80% | 1040 (55.2) | <0.0001 |
| 1884 | Free | amlo + val + HCTZ | 12 | PDC ≥ 80% | 629 (33.4) | ||
| Hsu (2015) [27] – Obs | 5725 | SPC | ARB/thiazide diuretic | 24 | MPR ≥ 80% | 1747 (30.5) | NR |
| 1623 | Free | ARB + thiazide diuretic | 24 | MPR ≥ 80% | 371 (22.9) | ||
| Degli Esposti (2014) [25] – Obs | 239 | SPC | olm/amlo | 6 | PDC ≥ 80% | 188 (78.7) | NR |
| 20 769 | Free | Not specified | 6 | PDC ≥ 80% | 13 084 (63) | ||
| Xie (2014) [47] – Obs | 8516 | SPC (triple-pill) | olm/amlo/HCTZ or val/amlo/HCTZ | 12 | PDC ≥ 80% | 4710 (55.3) | <0.0001 |
| 7842 | Mix (2 pills) | olm/amlo + HCTZ or val/amlo + HCTZ, or olm/HCTZ + amlo, or val/HCTZ + amlo | 12 | PDC ≥ 80% | 3171 (40.4) | ||
| 1107 | Free (3 pills) | olm + alm + HCTZ or val + alm + HCTZ | 12 | PDC ≥ 80% | 361 (32.6) | ||
| Panjabi (2013) [39] – Obs | 4005 | Mix (2 pills) | amlo/HCTZ + ARB | 34.2 | PDC ≥ 80% | 1033 (25.8) | <0.001 |
| 1335 | Free (3 pills) | amlo + HCTZ + ARB | 34.6 | PDC ≥ 80% | 184 (13.8) | ||
| 6082 | Mix (2 pills) | amlo/HCTZ + ACEi | 33.6 | PDC ≥ 80% | 1448 (23.8) | <0.001 | |
| 3041 | Free (3 pills) | amlo + HCTZ + ACEi | 33.3 | PDC ≥ 80% | 487 (16.0) | ||
| 609 | Mix (2 pills) | amlo/HCTZ + BB | 34.7 | PDC ≥ 80% | 173 (28.4) | <0.001 | |
| 1218 | Free (3 pills) | amlo + HCTZ + BB | 35.6 | PDC ≥ 80% | 166 (13.6) | ||
| (b) Measures of persistencec | |||||||
| Bramlage (2018) [22] – Obs | 10 938 | SPC | ram/amlo | 12 | Prescription fill | 7186 (65.7) | <0.001 |
| 60 525 | Free | ram + amlo | 12 | Prescription fill | 29 415 (48.6) | ||
| 1413 | SPC | cand/amlo | 12 | Prescription fill | 784 (55.5) | <0.001 | |
| 9082 | Free | cand + amlo | 12 | Prescription fill | 3914 (43.1) | ||
| Lauffenburger (2017) [31] – Obs | 79 958 | SPC | Not specified | 12 | Prescription refill | 40 938 (51.2) | NR |
| 383 269 | Monotherapy | Not specified | 12 | Prescription refill | 164 806 (43) | ||
| Simons (2017) [42] – Obs | 9340 (700 for persistence calculation) | SPC | amlo/per | 42 | Prescription refill | 350 (50) | NR |
| 3093 (78 for persistence calculation) | Free | amlo + per | 42 | Prescription refill | 21 (27) | ||
| Hsu (2015) [27] – Obs | 5725 | SPC | ARB/thiazide diuretic | 24 | Prescription refill | 1494 (26.1) | <0.0001 |
| 1623 | Free | ARB + thiazide diuretic | 24 | Prescription refill | 317 (19.5) | ||
| Machnicki (2015) [34] – Obs | 1884 | SPC | amlo/val/HCTZ | 12 | 30-day Tx gap | 882 (46.8) | <0.0001 |
| 1884 | Free | amlo + val + HCTZ | 12 | 30-day Tx gap | 445 (23.6) | ||
| Xie (2014) [47] – Obs | 8516 | SPC (triple-pill) | olm/amlo/HCTZ or val/amlo/HCTZ | 12 | Prescription refill | 7541 (88.55) | <0.0001 |
| 7842 | Mix (2 pills) | olm/amlo + HCTZ or val/amlo + HCTZ, or olm/HCTZ + amlo, or val/HCTZ + amlo | 12 | Prescription refill | 6363 (81.14) | ||
| 1107 | Free (3 pills) | olm + alm + HCTZ or val + alm + HCTZ | 12 | Prescription refill | 869 (78.5) | ||
ACEi, angiotensin-converting enzyme inhibitor; amlo, amlodipine; ARB, angiotensin 1 receptor (AT1); BB, beta-blocker; cand, candesartan; CCB, calcium channel blocker; chlo, chlorthalidone; HCTZ, hydrochlorothiazide; medox, medoximil; MPR, medication possession ratio; NR, not reported; Obs, observational; olm, olmesartan; PDC, proportion of days covered; per, perindopril; ram, ramipril; RCT, randomized-controlled trial; SPC, single-pill combination; tel, telmisartan; val, valsartan.
aN (%) adherent or persistent based on study criteria.
bNedogoda et al (2017) (RCT) reported ‘very good’ adherence at 97.6 ± 6.4% (undefined measure) across the whole study population but did not differentiate between SPC and free-combination therapy [38]. Tung et al. (2015) reported mean PDC and is not included in the table [44]. Verma et al. (2017) (Obs) reported median PDC and is not included in the table [14]. Kumagia et al. (2013) (Obs) adherence was self-reported ingestion and is not included in the table [30]. Simonyi et al. (2016) (Obs) compared SPC of two different drug combinations and is not included in the table (no coadministered therapy comparator) [43].
cTung et al. (2015) (Obs) reported data as mean persistence days and is not included in table [44].