The association of angiotensin receptor blocker-based combination therapy with persistence and adherence in newly treated, uncomplicated hypertensive patients

Figures & data

Figure 1 Flow of study enrollment.

Abbreviations: ARB, angiotensin receptor blocker; CCB, dihydropyridine calcium channel blocker; TD, thiazide diuretic.

Table 1 Baseline characteristics of study cohorts

Characteristics	Overall (N=40,350)	SPC (N=20,175)	FEC (N=20,175)	P-value	Overall (N=90,506)	ARB + TD (N=45,253)	ARB + CCB (N=45,253)	P-value
Age in years
Mean ± SD	56.1±13.8	56.1±13.8	56.1±13.9	0.99	52.9±11.6	53.0±11.6	52.9±11.6	0.53
18–64, n (%)	29,351 (72.7)	14,660 (72.7)	14,691 (72.8)	0.63	76,090 (84.1)	38,039 (84.1)	38,051 (84.1)	0.99
65–79, n (%)	8,573 (21.7)	4,318 (21.8)	4,255 (21.5)		12,439 (13.7)	6,223 (13.8)	6,216 (13.7)
≥80, n (%)	2,426 (6.1)	1,197 (6.1)	1,229 (6.2)		1,977 (2.2)	991 (2.2)	986 (2.2)
Sex, male, n (%)	23,708 (58.8)	11,867 (58.8)	11,841 (58.7)	0.79	56,458 (62.4)	28,247 (62.4)	28,211 (62.3)	0.81
Insurance type
Health insurance, n (%)	38,274 (94.9)	19,212 (95.2)	19,062 (94.5)	0.01	87,485 (96.7)	43,753 (96.7)	43,732 (96.6)	0.70
Medical aid, n (%)	2,076 (5.1)	963 (4.8)	1,113 (5.5)		3,021 (3.3)	1,500 (3.3)	1,521 (3.4)
Charlson Comorbidity Index score
0, n (%)	31,646 (78.4)	15,824 (78.4)	15,822 (78.4)	0.98	77,552 (85.7)	38,745 (85.6)	38,807 (85.8)	0.58
1, n (%)	8,704 (21.6)*	4,351 (21.6)*	4,353 (10.8)*		10,073 (11.1)	5,081 (11.2)	4,992 (11.0)
≥2, n (%)					2,881 (3.2)	1,427 (3.2)	1,454 (3.2)
Specific diseases
Dementia, n (%)	1 (0.0)	0 (0.0)	1 (0.0)	–	784 (0.9)	350 (0.8)	434 (1.0)	<0.01
Depression, n (%)	19 (0.1)	10 (0.1)	9 (0.0)	0.82	2,849 (3.2)	1,513 (3.3)	1,336 (3.0)	<0.01
Dyslipidemia, n (%)	64 (0.2)	35 (0.2)	29 (0.1)	0.45	24,073 (26.6)	12,401 (27.4)	11,672 (25.8)	<0.01
Therapeutic class of index therapy
ARB + TD, n (%)	14,423 (35.7)	11,352 (56.3)	3,071 (15.2)	<0.01	–	–	–	–
ARB + CCB, n (%)	25,927 (64.3)	8,823 (43.7)	17,104 (84.8)		–	–	–	–

Note:

* Patients having a Charlson Comorbidity Index score of 1 or more.

Abbreviations: ARB, angiotensin receptor blocker; CCB, dihydropyridine calcium channel blocker; FEC, free equivalent combination; SPC, single pill combination; TD, thiazide diuretic.

Table 2 Comparison of persistence and adherence between cohorts

Outcome variables	Overall (N=40,350)	SPC (N=20,175)	FEC (N=20,175)	P-value	Overall (N=90,506)	ARB + TD (N=45,253)	ARB + CCB (N=45,253)	P-value
Treatment persistence
At month 6, n (%)	27,833 (69.0)	14,772 (73.2)	13,090 (64.9)	<0.01	66,120 (73.1)	32,915 (72.7)	33,205 (73.4)	0.03
At month 12, n (%)	25,332 (62.8)	13,390 (66.4)	11,942 (59.2)	<0.01	59,835 (66.1)	29,863 (66.0)	29,972 (66.2)	0.44
Duration, days, mean ± SD	274.1±126.1	285.5±120.5	262.6±130.5	<0.01	285.0±120.6	284.4±120.9	285.7±120.2	0.09
Initial drug persistence
At month 6, n (%)	19,566 (48.5)	10,897 (54.0)	8,671 (43.0)	<0.01	49,901 (55.1)	24,034 (53.1)	25,867 (57.2)	<0.01
At month 12, n (%)	15,410 (38.2)	8,459 (41.9)	6,948 (34.4)	<0.01	39,041 (43.1)	18,596 (41.1)	20,445 (45.2)	<0.01
Duration, days, mean ± SD	202.0±143.2	228.9±129.4	175.1±151.1	<0.01	231.8±129.4	226.1±129.5	237.4±129.1	<0.01
Treatment adherence
Mean ± SD	0.8±0.3	0.8±0.3	0.7±0.3	<0.01	0.8±0.3	0.79±0.28	0.8±0.3	0.02
MPR groupa				<0.01				0.06
Low, n (%)	7,094 (17.6)	2,756 (13.7)	4,338 (21.5)		12,697 (14.0)	6,472 (14.3)	6,225 (13.8)
Intermediate, n (%)	6,710 (16.6)	3,597 (17.8)	3,113 (15.4)		16,514 (18.3)	8,220 (18.2)	8,294 (18.3)
Fully adherent, n (%)	26,546 (65.8)	13,822 (68.5)	12,724 (63.1)		61,295 (67.7)	30,561 (67.5)	30,734 (67.9)

Note:

a We categorized patients as fully adherent (MPR ≥0.8), intermediate (MPR 0.4–0.79), or low (MPR <0.4).

Abbreviations: ARB, angiotensin receptor blocker; CCB, dihydropyridine calcium channel blocker; FEC, free equivalent combination; MPR, medication possession ratio; SPC, single pill combination; TD, thiazide diuretic.

Table 3 Comparison of 1-year treatment persistence, initial treatment persistence, and adherence

Outcome variables	Adjusted hazard ratio or odds ratio [95% CI]
	SPC vs FEC (reference)	ARB + CCB vs ARB + TD (reference)
One-year treatment persistence	1.33 (1.28, 1.39)	1.02 (0.99, 1.04)
Initial treatment persistence	1.61 (1.56, 1.64)	1.12 (1.10, 1.14)
One-year treatment adherence	1.31 (1.25, 1.37)	1.03 (1.00, 1.06)

Notes: Cox proportional hazard regression and logistic regression analyses were performed to compare persistence and adherence, respectively. Covariates were adjusted for age, sex, insurance type, Charlson Comorbidity Index score, and underlying disease (dementia, depression, and dyslipidemia). Comparisons between SPC and FEC were also adjusted for the type of ARB combination.

Abbreviations: ARB, angiotensin receptor blocker; CCB, dihydropyridine calcium channel blocker; FEC, free equivalent combination; SPC, single pill combination; TD, thiazide diuretic.

Data availability

The data could not be shared because the access to raw data of the Korean HIRA service is regulated by the Rules for Data Exploration and Utilization of the HIRA.