Comparative Effectiveness of Antihypertensive Therapeutic Classes and Treatment Strategies in the Initiation of Therapy in Primary Care Patients: A Distributed Ambulatory Research in Therapeutics Network (DARTNet) Study

Michael R. Bronsert; William G. Henderson; Robert Valuck; Patrick Hosokawa; Karl Hammermeister

doi:10.3122/jabfm.2013.05.130048

Article Figures & Data

Figures

Tables

Download figure
Open in new tab
Figure 1.
Timeline defining key events in the study for patients initially using antihypertensive agents. BP, blood pressure; Rx, prescription.
Download figure
Open in new tab
Figure 2.
STROBE diagram of included patients with initial use of antihypertensive agents (anti-HTN). Apt, appointment; BP, blood pressure; CKD, chronic kidney disease.

Tables

Figures

View popup

Table 1. Population Characteristics

Selected Risk-Adjustment Variables	Study Cohort (n = 8676)
Female sex	4693 (54.1)
Age at index (years), mean (SD)	54.4 (13.4)
Body mass index (kg/m²), mean (SD)	30.7 (6.9)
Index SBP (mm Hg), mean (SD)	148.7 (15.1)
Index DBP (mm Hg), mean (SD)	90.4 (10.9)
Chronic kidney disease	854 (9.8)
Diabetes mellitus	1325 (15.3)
Hyperlipidemia diagnosis	2841 (32.8)
Hypertension diagnosis	5330 (61.4)
Follow-up duration (months)
Mean (SD)	6.3 (3.9)
Median (IQR)	6.5 (2.5–10.5)
Clinic visits within 1 year before index
Mean (SD)	3.9 (3.4)
Median (IQR)	3.0 (2.0–5.0)

Data are n (%) unless otherwise indicated.
DBP, diastolic blood pressure; IQR, interquartile range; SBP, systolic blood pressure; SD, standard deviation.

View popup

Table 2. Unadjusted Population Characteristics for Primary Care Patients With Initial Use of Monotherapy Antihypertensive Agents by Therapeutic Class

Characteristics	ACEI (n = 3131)	Thiazide (n = 1947)	Cardioselective β-blocker (n = 1029)	ARB (n = 533)	CCB (n = 529)	P^*
Female sex, n (%)	1442 (46.1)	1248 (64.1)	601 (58.4)	275 (51.6)	312 (59.0)	<.001
Age at index (years)	53.6 (13.0)	52.6 (13.0)	54.1 (14.4)	55.2 (12.4)	57.8 (14.7)	<.001
BMI (kg/m²)	30.9 (6.8)	31.1 (7.3)	28.9 (6.2)	30.4 (6.1)	29.7 (6.7)	<.001
Index systolic BP (mm Hg)	147.6 (15.0)	149.3 (13.4)	147.7 (15.4)	147.8 (14.9)	149.5 (15.7)	<0.001
Index diastolic BP (mm Hg)	90.1 (10.7)	91.5 (10.1)	90.1 (10.9)	89.7 (10.4)	89.4 (11.4)	<.001
CKD, n (%)	221 (7.1)	127 (6.5)	118 (11.5)	52 (9.8)	94 (17.8)	<.001
Diabetes, n (%)	789 (25.2)	89 (4.6)	75 (7.3)	109 (20.5)	29 (5.5)	<.001
Hyperlipidemia, n (%)	1177 (37.6)	557 (28.6)	296 (28.8)	196 (36.8)	155 (29.3)	<.001
Hypertension, n (%)	1902 (60.8)	1335 (68.6)	506 (49.2)	258 (48.4)	279 (52.7)	<.001
Follow-up duration (months)	6.5 (3.8)	5.9 (3.9)	6.3 (3.9)	6.2 (3.8)	6.4 (4.0)	<.001
Number of clinic visits	3.8 (3.2)	3.9 (3.2)	4.2 (4.0)	3.6 (3.4)	4.3 (3.8)	<.001

Data are mean (standard deviation) unless otherwise indicated.
↵* P values were from analysis of variance (ANOVA) or logistic regression and test the overall effect across the five therapeutic classes.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CKD, chronic kidney disease; thiazide, thiazide and thiazide-like diuretics.

View popup

Table 3. Unadjusted Population Characteristics for Primary Care Patients with Initial Use of Antihypertensive Agents by Treatment Strategy

Characteristics	FDC (n = 795)	FEC (n = 712)	Monotherapy (n = 7169)	P^*
Female sex, n (%)	373 (46.9)	442 (62.1)	3878 (44.7)	<.001
Age at index (years)	52.9 (12.6)	61.9 (12.9)	53.8 (13.4)	<.001
BMI (kg/m²)	31.9 (7.2)	30.4 (6.9)	30.6 (6.8)	<.001
Index systolic BP (mm Hg)	153.8 (16.5)	147.8 (16.4)	148.2 (14.7)	<.001
Index diastolic BP (mm Hg)	94.3 (11.1)	85.9 (12.2)	90.4 (10.6)	<.001
CKD, n (%)	54 (6.8)	188 (26.4)	612 (7.1)	<.001
Diabetes, n (%)	66 (8.3)	168 (23.6)	1091 (12.6)	<.001
Hyperlipidemia, n (%)	251 (31.6)	209 (29.4)	2381 (27.4)	.09
Hypertension, n (%)	594 (74.7)	456 (64.0)	4280 (49.3)	<.001
Follow-up duration (months)	6.2 (3.8)	6.7 (3.9)	6.3 (3.9)	.02
Number of clinic visits	3.0 (2.8)	4.2 (3.8)	3.9 (3.4)	<.001

Data are mean (standard deviation) unless otherwise indicated.
↵* P values were from analysis of variance (ANOVA) or logistic regression and test the overall effect across the three treatment strategies.
BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; FDC, fixed-dose combination; FEC, free-equivalent combination.

View popup

Table 4. Therapeutic Classes for Initial Use Patients Initiated on a Fixed-Dose Combination (FDC) or Free-Equivalent Combination (FEC)

Therapeutic class	FDC (n = 795)	FEC (n = 712)
ACEI and thiazide	397 (49.9)	187 (26.3)
ARB and thiazide	250 (31.5)	39 (5.5)
ACEI and CCB	83 (10.4)	80 (11.2)
ACEI and β-blocker	0 (0)	140 (19.7)
β-Blocker and thiazide	34 (4.3)	81 (11.4)
CCB and thiazide	0 (0)	73 (10.3)
ARB and CCB	31 (3.9)	28 (3.9)
β-Blocker and CCB	0 (0)	38 (5.3)
ARB and β-blocker	0 (0)	34 (4.8)
ACEI and ARB	0 (0)	12 (1.7)

Data are number (%).
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; β-blocker, cardioselective β-blocker; CCB, calcium channel blocker; thiazide, thiazide and thiazide-like diuretics.

View popup

Table 5. Unadjusted and Risk-Adjusted Change^* in Blood Pressure (BP) and Goal Attainment Rates by Antihypertensive Therapeutic Classes Initiated as Monotherapy

Outcomes	ACEI (n = 3131)	Thiazide (n = 1947)	Cardioselective β-blocker (n = 1029)	ARB (n = 533)	CCB (n = 529)
Systolic BP (mm Hg)
At index	147.6 (15.0)	149.3 (13.4)	147.7 (15.4)	147.8 (14.9)	149.5 (15.7)
At follow-up	133.6 (16.2)	136.6 (14.9)	134.9 (16.9)	135.1 (15.8)	136.7 (17.1)
Unadjusted change	−14.0 (18.1)	−12.7 (17.1)	−12.8 (18.2)	−12.7 (17.7)	−12.8 (19.5)
Risk-adjusted change	−13.4 (10.3)	−14.1 (9.3)^{^†}	−13.4 (10.8)	−13.3 (10.4)	−14.0 (10.9)^{^‡}
Diastolic BP (mm Hg)
At index	90.1 (10.7)	91.5 (10.1)	90.1 (10.9)	89.7 (10.4)	89.4 (11.4)
At follow-up	81.8 (10.1)	84.6 (10.5)	82.8 (10.8)	82.5 (10.5)	82.0 (11.1)
Unadjusted change	−8.3 (11.4)^{^†}	−6.8 (11.3)	−7.4 (11.3)	−7.1 (11.3)	−7.3 (11.9)
Risk-adjusted change	−7.9 (6.6)	−8.2 (6.3)^{^†}	−7.7 (6.8)	−7.6 (6.4)	−7.5 (7.0)
Goal attainment, n (%)
Unadjusted at goal	1465 (46.8)^{^§}	826 (42.4)	508 (49.4)^{^‖}	229 (43.0)	239 (45.2)
Risk-adjusted at goal	1495 (47.8)^{^†}	776 (39.9)	472 (45.9)^{^¶}	230 (43.1)	234 (44.2)

Data are mean (standard deviation) unless otherwise indicated.
↵* Unadjusted P values were from analysis of variance or logistic regression, whereas risk-adjusted P values were from analysis of covariance or logistic regression.
↵† ACEI vs thiazide, P < .001.
↵‡ ACEI vs CCB, P = .04.
↵§ ACEI vs thiazide, P = .02.
↵‖ β-blocker vs thiazide, P = .003.
↵¶ β-blocker vs thiazide, P = .01.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; thiazide, thiazide and thiazide-like diuretics.

View popup

Table 6. Unadjusted and Risk-Adjusted Change in Blood Pressure (BP) and Goal Attainment Rates by Initial Antihypertensive Treatment Strategy

Outcomes	FDC(n = 795)	FEC(n = 712)	Monotherapy(n = 7169)	P Values^*
Outcomes	FDC(n = 795)	FEC(n = 712)	Monotherapy(n = 7169)	FDC vs FEC	FDC vs Mono	FEC vs Mono
Systolic BP (mm Hg)
At index	153.8 (16.5)	147.8 (16.4)	148.2 (14.7)	<.001	<.001	.47
At follow-up	132.3 (16.1)	137.5 (18.6)	134.9 (16.1)	<.001	<.001	<.001
Unadjusted change	−21.5 (20.5)	−10.3 (20.7)	−13.3 (17.9)	<.001	<.001	<.001
Risk-adjusted change	−17.3 (11.6)	−12.0 (11.5)	−13.6 (10.2)	<.001	<.001	.04
Diastolic BP (mm Hg)
At index	94.3 (11.1)	85.9 (12.2)	90.4 (10.6)	<.001	<.001	<.001
At follow-up	82.0 (10.6)	79.8 (11.7)	82.8 (10.5)	<.001	.06	<.001
Unadjusted change	−12.3 (12.3)	−6.1 (12.5)	−7.6 (11.4)	<.001	<.001	.003
Risk-adjusted change	−10.1 (6.8)	−6.0 (7.5)	−7.9 (6.6)	<.001	<.001	.34
Goal attainment, n (%)
Unadjusted at goal	440 (55.4)	226 (37.4)	3267 (45.6)	<.001	<.001	<.001
Risk-adjusted at goal	455 (57.2)	303 (42.5)	3216 (44.9)	<.001	<.001	.69

Data are mean (standard deviation) unless otherwise indicated.
↵* Unadjusted P values were calculated using analysis of variance or logistic regression, whereas risk-adjusted P values were from analysis of covariance or logistic regression.
FDC, fixed-dose combination; FEC, free-equivalent combination.