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Research ArticleOriginal Research

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 and Karl Hammermeister
The Journal of the American Board of Family Medicine September 2013, 26 (5) 529-538; DOI: https://doi.org/10.3122/jabfm.2013.05.130048
Michael R. Bronsert
the Colorado Health Outcomes Program (MRB, WGH, PH, KH) and the Division of Cardiology (KH), University of Colorado School of Medicine, Aurora; the Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora (WGH); the Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora (RV).
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William G. Henderson
the Colorado Health Outcomes Program (MRB, WGH, PH, KH) and the Division of Cardiology (KH), University of Colorado School of Medicine, Aurora; the Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora (WGH); the Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora (RV).
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Robert Valuck
the Colorado Health Outcomes Program (MRB, WGH, PH, KH) and the Division of Cardiology (KH), University of Colorado School of Medicine, Aurora; the Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora (WGH); the Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora (RV).
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Patrick Hosokawa
the Colorado Health Outcomes Program (MRB, WGH, PH, KH) and the Division of Cardiology (KH), University of Colorado School of Medicine, Aurora; the Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora (WGH); the Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora (RV).
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Karl Hammermeister
the Colorado Health Outcomes Program (MRB, WGH, PH, KH) and the Division of Cardiology (KH), University of Colorado School of Medicine, Aurora; the Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora (WGH); the Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora (RV).
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Article Figures & Data

Figures

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    Figure 1.

    Timeline defining key events in the study for patients initially using antihypertensive agents. BP, blood pressure; Rx, prescription.

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    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

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    Table 1. Population Characteristics
    Selected Risk-Adjustment VariablesStudy Cohort (n = 8676)
    Female sex4693 (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 disease854 (9.8)
    Diabetes mellitus1325 (15.3)
    Hyperlipidemia diagnosis2841 (32.8)
    Hypertension diagnosis5330 (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.

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    Table 2. Unadjusted Population Characteristics for Primary Care Patients With Initial Use of Monotherapy Antihypertensive Agents by Therapeutic Class
    CharacteristicsACEI (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 visits3.8 (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
    CharacteristicsFDC (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 visits3.0 (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.

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    Table 4. Therapeutic Classes for Initial Use Patients Initiated on a Fixed-Dose Combination (FDC) or Free-Equivalent Combination (FEC)
    Therapeutic classFDC (n = 795)FEC (n = 712)
    ACEI and thiazide397 (49.9)187 (26.3)
    ARB and thiazide250 (31.5)39 (5.5)
    ACEI and CCB83 (10.4)80 (11.2)
    ACEI and β-blocker0 (0)140 (19.7)
    β-Blocker and thiazide34 (4.3)81 (11.4)
    CCB and thiazide0 (0)73 (10.3)
    ARB and CCB31 (3.9)28 (3.9)
    β-Blocker and CCB0 (0)38 (5.3)
    ARB and β-blocker0 (0)34 (4.8)
    ACEI and ARB0 (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
    OutcomesACEI (n = 3131)Thiazide (n = 1947)Cardioselective β-blocker (n = 1029)ARB (n = 533)CCB (n = 529)
    Systolic BP (mm Hg)
        At index147.6 (15.0)149.3 (13.4)147.7 (15.4)147.8 (14.9)149.5 (15.7)
        At follow-up133.6 (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 index90.1 (10.7)91.5 (10.1)90.1 (10.9)89.7 (10.4)89.4 (11.4)
        At follow-up81.8 (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 goal1465 (46.8)§826 (42.4)508 (49.4)‖229 (43.0)239 (45.2)
        Risk-adjusted at goal1495 (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
    OutcomesFDC(n = 795)FEC(n = 712)Monotherapy(n = 7169)P Values*
    FDC vs FECFDC vs MonoFEC vs Mono
    Systolic BP (mm Hg)
        At index153.8 (16.5)147.8 (16.4)148.2 (14.7)<.001<.001.47
        At follow-up132.3 (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 index94.3 (11.1)85.9 (12.2)90.4 (10.6)<.001<.001<.001
        At follow-up82.0 (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 goal440 (55.4)226 (37.4)3267 (45.6)<.001<.001<.001
        Risk-adjusted at goal455 (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.

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The Journal of the American Board of Family     Medicine: 26 (5)
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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
The Journal of the American Board of Family Medicine Sep 2013, 26 (5) 529-538; DOI: 10.3122/jabfm.2013.05.130048

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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
The Journal of the American Board of Family Medicine Sep 2013, 26 (5) 529-538; DOI: 10.3122/jabfm.2013.05.130048
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