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Research

Uptake of direct oral anticoagulants in primary care: an ecological and economic study

Rachel Denholm, Howard Thom, William Hollingworth and Rupert Payne
BJGP Open 2020; 4 (2): bjgpopen20X101033. DOI: https://doi.org/10.3399/bjgpopen20X101033
Rachel Denholm
1 Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
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  • For correspondence: r.denholm@bristol.ac.uk
Howard Thom
1 Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
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William Hollingworth
2 Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
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Rupert Payne
1 Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
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  • Figure 1.
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    Figure 1. Variation in the relative uptake of DOACs across CCGs, January to March 2017

    DOAC = direct oral anticoagulant; CCG = clinical commissioning groups. Anticoagulants include dabigatran, rivaroxaban, apixaban, and edoxaban (DOACs) and warfarin. Percentage of patients dispensed anticoagulants given a DOAC calculation = (Total number of patients dispensed a DOAC/Total number of patients dispensed any anticoagulant) multiplied by 100

  • Figure 2.
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    Figure 2. Average (mean) quantity of anticoagulants (DOACs and warfarin) dispensed by a general practice in England, by year quarter.

    DOAC = direct oral anticoagulant. A: Average (mean) quantity of DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) dispensed per practice. B: Average (mean) quantity of all anticoagulants and warfarin dispensed per practice. C: Average (mean) relative uptake of DOACs per practice (total quantity of DOACs/total quantity of anticoagulants multiplied by 100) The grey shaded areas represent 95% confidence intervals (mean ±1.96*SD)

  • Figure 3.
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    Figure 3. Rates of ischaemic stroke, intracranial bleeding and gastrointestinal bleeding, per 1000 population, by year quarter.

    GI = gastrointestinal. Ischaemic stroke defined as any I63 ICD-10 code occurring in the primary diagnostic position for any care episode within the first 7 days of admission. Intracranial bleeding (ICD-10 codes I160 to I62) and gastrointestinal bleeding (K25.0/2/4/6-K28.0/2/4/6, K92.0–2) recorded as the primary diagnosis for any episode of care. Denominator data were based on practice population sizes obtained from quarterly reports of patient numbers to NHS Digital, and where missing, annual figures recorded as part of the English primary care pay-for-performance scheme, the Quality and Outcomes Framework.

  • Figure 4.
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    Figure 4. Average (mean) total cost of anticoagulants and associated outcomes, per 1000 patients.

    DOAC = direct oral anticoagulant; CCG = clinical commissioning group. A: Average (mean) total cost per 1000 patients stratified by percentage anticoagulants a DOAC; January to March 2017. B: Average (mean) total cost per 1000 patients stratified by CCG; January to March 2017. C: Average (mean) total cost per 1000 patients stratified by year quarter. Total cost includes cost of anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin), management costs of warfarin, and costs associated with a hospital admission for ischaemic stroke, and intracranial and gastrointestinal bleed (see Table S1). The grey shaded areas in Figures A and C represent 95% confidence intervals (mean ±1.96). Figure A restricted to practices within the 95% range of outcome (10%–50% anticoagulants dispensed a DOAC). Analysis excludes practices with practice population <50 (n = 1).

  • Figure 5.
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    Figure 5. Marginal effect of total cost per 1000 patients, by change in relative uptake of DOACs, with CCG distribution as of January to March, 2017.

    DOAC = direct oral anticoagulant; CCG = clinical commissioning group. Generalised linear models (GLMs) were used to estimate the costs associated with a change in relative uptake of DOACs, whereby the logarithm of the conditional expectation of the total cost was estimated, and the relationship of the mean to variance in the outcome data were assessed and modelled (models presented in Table S4). CCG was included as a random effect to account for clustering and robust standard errors were used to allow for potential misspecification of the link and family function. Marginal effects represent a change in the outcome for an increase in the exposure, keeping all other covariates at their observed levels, and averaged over all patients. Models were adjusted for demographic, clinical and practice factors CCG distribution reflects the average DOAC uptake in general practices within a CCG. NHS Digital did not have information available before 1 April 2013 so the final models are restricted to after this date.

Tables

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    Table 1. Association between practice-level factors (per SD) and the relative uptake of DOACs, January to March 2017 (general practices n = 6480, CCG n = 195)
    Univariable analysisFull model
    OR (95% CI) P valueOR (95% CI) P value
    Patient demographics
     % malesa 0.98 (0.97 to 0.98)<0.0011.00 (0.99 to 1.00)0.708
     % aged ≥65 yearsa 0.99 (0.99 to 1.00)<0.0010.98 (0.97 to 0.99)<0.001
     Ratio 85:651.05 (1.05 to 1.06)<0.0011.05 (1.05 to 1.06)<0.001
     Practice population size1.00 (1.00 to 1.01)<0.0011.00 (1.00 to 1.00)0.915
    Disease prevalence
     AF1.00 (1.00 to 1.01)<0.0011.02 (1.01 to 1.03)0.001
     CHD0.99 (0.98 to 0.99)<0.0011.00 (0.99 to 1.01)0.946
     CKD0.99 (0.99 to 0.99)<0.0011.00 (1.00 to 1.00)0.694
     DM0.93 (0.93 to 0.94)<0.0010.94 (0.93 to 0.94)<0.001
    GP Patient Survey
     Experience1.01 (1.01 to 1.02)<0.0011.00 (1.00 to 1.01)0.628
     Preferred GP1.01 (1.01 to 1.01)<0.0011.01 (1.01 to 1.01)<0.001
     Trust1.01 (1.00 to 1.01)<0.0011.00 (0.99 to 1.00)0.087
    Total QOF scoreb 1.00 (1.00 to 1.01)0.0601.00 (1.00 to 1.00)0.771
    CCG variance
     95% mid-rangec 1.97 (1.74 to 2.28)<0.0011.99 (1.76 to 2.31)<0.001
    • Multilevel logistic regression models with a binomial distribution were used, with CCG included as a random effect to account for clustering. All measures were standardised (using sample mean values and SDs), and OR represent the odds of a patient dispensed an anticoagulant (DOAC and warfarin) given a DOAC, for a unit increase in the exposure of interest. DOACs include dabigatran, rivaroxaban, apixaban, and edoxaban

    • aDenominator data used was practice-list size in January–March 2017. bTotal QOF score is total QOF points achieved as a percentage of all achievable points (max 559) for 2015–2016. cCalculated from the variance of the random effect (σ2) and is given by e2 ×1.96×σ and represents the odds ratio comparing a practice at the 2.5th percentile of the distribution of practices to one at the 97.5th percentile

    • AF
      atrial fibrillation
      CCG
      clinical commissioning group
      CHD
      coronary heart disease
      CI
      confidence intervals
      CKD
      chronic kidney disease
      DM
      diabetes mellitus
      DOAC
      direct oral anticoagulant
      GP
      general practitioner
      HYP
      hypertension
      OD
      odd ratio
      QOF
      Quality and Outcomes Framework
      SD
      standard deviation
    • View popup
    Table 2. Marginal effects of number of events and cost per 1000 patients per year quarter, associated with changes in the relative uptake of direct oral anticoagulants
    Number of ischaemic strokes, per 1000 populationNumber of bleeds, per 1000 populationTotal cost per 1000 population
    Marginal effect (95% CI)Marginal effect (95% CI)Marginal effect (99% CI)
    per 5% increase0.000 (0.000 to 0.000)0.000 (0.000 to 0.000)£17.95 (£8.75 to £27.15)
    • CI = confidence intervals. Anticoagulants include dabigatran, rivaroxaban, apixaban, and edoxaban (DOACs) and warfarin. Number of bleeds includes gastrointestinal and cerebral bleeds. Total cost includes cost of anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin), management costs of warfarin, and costs associated with a hospital admission for ischaemic stroke, and intracranial and gastrointestinal bleed.

Supplementary Data

SUPPLEMENTARY MATERIALS

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    Supplementary material is not copyedited or typeset, and is published as supplied by the author(s). The author(s) retain(s) responsibility for its accuracy.

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Uptake of direct oral anticoagulants in primary care: an ecological and economic study
Rachel Denholm, Howard Thom, William Hollingworth, Rupert Payne
BJGP Open 2020; 4 (2): bjgpopen20X101033. DOI: 10.3399/bjgpopen20X101033

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Uptake of direct oral anticoagulants in primary care: an ecological and economic study
Rachel Denholm, Howard Thom, William Hollingworth, Rupert Payne
BJGP Open 2020; 4 (2): bjgpopen20X101033. DOI: 10.3399/bjgpopen20X101033
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Keywords

  • anticoagulant
  • warfarin
  • economics
  • Hospitalization
  • direct oral anticoagulants
  • commissioning
  • randomized controlled trials
  • primary health care
  • general practice

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