Article Text

Original research
Disparities in the real-world prescription pattern of oral anticoagulants for US Medicare beneficiaries: a geospatial analysis
  1. Jingrui Zou1,
  2. Dong Liang2,
  3. Yong Zhu3
  1. 1Department of Scientific Affairs, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  2. 2Chesapeake Biological Laboratory, University of Maryland Center for Environmental Science, Solomons, Maryland, USA
  3. 3Wayzek Science, St Paul, Minnesota, USA
  1. Correspondence to Dr Yong Zhu; yzhu{at}wayzek.com

Abstract

Objectives This study was conducted to examine urban–rural differences in the real-world prescribing pattern of oral anticoagulants and geographic variations in the prescribing pattern among clinicians serving Medicare beneficiaries in the USA.

Design A cross-sectional study.

Setting A real-world setting.

Participants 232 665 clinicians who prescribed oral anticoagulants for Medicare beneficiaries from the 2020 Medicare Provider Utilisation and Payment Data were classified as warfarin only, direct oral anticoagulants (DOACs) only or warfarin+DOAC prescribers.

Main outcome measures Urban–rural differences in the prescribing patterns were examined using multivariate multinominal logistic regression analysis. A geospatial analysis was conducted to estimate standardised prescriber ratios (SPR) for DOAC only or warfarin only prescribers versus warfarin+DOAC prescribers to illustrate hot and cold spots for DOAC adoption in the USA.

Results 92% of clinicians who prescribed oral anticoagulants prescribed DOAC in 2020. Clinicians from rural regions were more likely to prescribe warfarin only (adjusted OR=1.335, 95% CI=(1.281 to 1.391)) and DOAC only (adjusted OR=2.052, 95% CI=(1.999 to 2.106)), compared with clinicians from urban regions. Hot spots for SPR of DOAC only versus warfarin+DOAC prescribers were mostly found in California, southern and southeastern states; cold spots were mostly found in Minnesota and Iowa. Hot spots for SPR of warfarin only versus warfarin+DOAC prescribers were mostly found in several metropolitan areas on the west coast and in Midwest; cold spots were mostly found on the east coast.

Conclusions Urban–rural status of clinicians was associated with their prescribing patterns of oral anticoagulants. The study identifies geographical heterogeneity in DOAC adoption and highlights gaps that may need to be addressed for increased accessibility of DOAC for patients in need.

  • cardiac epidemiology
  • epidemiology
  • health equity

Data availability statement

Data are available in a public, open access repository. Data used in the study are publicly available at https://data.cms.gov/provider-summary-by-type-of-service/medicare-part-d-prescribers.

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STRENGTHS AND LIMITATIONS OF THIS STUDY

  • Greater granularity in geographical disparities in clinicians’ prescribing pattern for oral anticoagulants was achieved through assessment of data at the zip code level and visualisation at the county level.

  • Patient-level data such as the type of cardiovascular disorders were not available in the analysis; it was not known how much this would contribute to the observed geographical differences.

  • The study focused on clinicians who provided services for Medicare beneficiaries in 2020, which may limit its generalisability.

Introduction

Oral anticoagulants play a critical role in managing or preventing thromboembolic events in patients at risk.1 Historically, warfarin has been the most widely used anticoagulant for many decades.2 Since 2010, several direct oral anticoagulants (DOACs) have been approved by US Food and Drug Administration with accumulating evidence showing these new alternatives have comparable or superior safety and efficacy than warfarin,3–6 with improved convenience given no requirement for routine laboratory and clinical monitoring of coagulation status.7 Recent clinical guidelines, such as the 2019 guidelines for management of patients with atrial fibrillation from the American Heart Association/American College of Cardiology Task Force in collaboration with Heart Rhythm Society,8 as well as the 2020 guidelines from American Society of Hematology for management of venous thromboembolism,9 have recommended use of DOAC over warfarin. Despite evidence of benefits and recommendations in clinical guidelines, barriers such as provider awareness, financial challenges and clinical knowledge may have impeded the fully adoption of DOAC in clinical settings.10

Previous studies indicated that older patients were more likely to use DOAC11–13 although it has also been reported there was a challenge in DOAC dosing in older patients.14 As such, studies on DOAC prescribing patterns for older adults are of particular relevance. Two studies examined clinician prescribing patterns of oral anticoagulants for Medicare beneficiaries from 2013 to 201515 and 2013 to 201816 using clinician-level data. Both studies reported increased DOAC shares over time, and cardiologists prescribed the largest volume of DOAC.15 16 Moreover, prescriber inertia was found such that those clinicians who did not use DOAC in 2013 were less likely to use DOAC in 2018.16 Research on additional prescriber characteristics may offer insights into how healthcare provider’s characteristics contribute to adoption of DOAC in their clinical practice.

Several studies also examined use of DOAC in rural settings in the US population using patient-level data. For example, Caverley et al17 reported that DOAC has a similar safety profile as warfarin in patients with obesity in a rural clinic. Brod et al18 found there was only a small increase in the percentage of patients with non-valvular atrial fibrillation receiving DOAC from a large rural healthcare system after the 2019 guidelines. Norby et al19 further examined urban–rural differences and reported rural patients with atrial fibrillation were less likely to receive DOAC. Nonetheless, there is a gap on urban–rural differences and geographical variations in the prescription pattern of oral anticoagulant using clinician-level data. Research on this topic may inform better healthcare resource allocation for policy-makers and identify opportunities for increased awareness or knowledge of DOAC among clinicians in regions with a lower rate of adoption.

This study used the year 2020 data from Medicare Provider Utilisation and Payment Public Use Files with the objective to examine urban–rural differences in prescribing patterns of oral anticoagulants for Medicare beneficiaries in the real world and investigate geographical variations in the adoption of DOAC in clinical settings.

Methods

Study design and data source

The present study is a retrospective observational study that used 2020 Medicare Provider Utilisation and Payment, Part D Prescribers—By Provider Public Use File20 and By Provider and Drug Public Use File21 from Centers for Medicare and Medicaid Services. Description and methodology used to create these data files are available elsewhere.22 Briefly, the ‘By Provider Public Use File’ contains certain information about clinicians (such as National Provider Identifier, name, specialty and gender) as well as their medical facility (such as address and Rural–Urban Commuting Area (RUCA) code) that served Medicare beneficiaries; and the ‘By Provider and Drug Public Use File’ included clinician-level information on drug prescription and drug cost, based on prescription events in both primary and secondary care settings incurred by Medicare beneficiaries with a Part D prescription drug plan in calendar year 2020.22 To reduce the risk of reidentification, the Public Use Files do not include any records derived from 10 or less claims for a given drug from a clinician.

Study population

Clinicians who prescribed at least 11 claims for any oral anticoagulant as recorded in the Public Use Files were included (n=235 255). Among these, 2375 clinicians from other geographical regions (ie, not the 50 US states and the District of Columbia) and 215 clinicians with unknown urban–rural status were then excluded, providing a total of 232 665 clinicians in the present study. Oral anticoagulants include both warfarin and DOAC (apixaban, dabigatran and rivaroxaban). Edoxaban (4766 claims from 324 clinicians) was not included due to its low prescription volume (0.02% of total DOAC claims), and betrixaban was not found in the 2020 Public Use Files, likely because no clinician prescribed at least 11 claims for Medicare beneficiaries in 2020. Both generic name and brand name of the drugs were used in identifying clinicians in the study population. Clinicians were classified as prescribing warfarin only, DOAC only or warfarin+DOAC, depending on whether claims for warfarin or DOAC were identified from their records in the data set.16

Patient and public involvement

Patients and the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Study measures

Characteristics of clinicians prescribing anticoagulants included specialty, gender, US census region, urban–rural status of their practising facility. Specialty was classified into cardiology, family medicine, internal medicine, advanced practice clinicians (nurses and physician assistants) and others.16 US census regions were defined by US Census Bureau23 and were coded based on the state of the clinician reported in the National Plan and Provider Enumeration System. Urban–rural status was recoded from the RUCA code for each clinician as urban providers or rural providers. RUCA codes are based on population density, commuting time and degree of urbanisation, with codes of 1–3 being urban and the rest being rural.24

Statistical analyses

Characteristics of clinicians by anticoagulants prescribing patterns were compared using χ2 tests. Multivariate multinominal logistic regression analysis was used to assess associations between urban–rural status of clinicians and their prescribing pattern of oral anticoagulants, adjusting for gender, specialty and US census region; those who prescribed warfarin+DOAC was the reference group as it had the largest sample size among the three groups. Adjusted ORs with 95% CIs were presented. A sensitivity analysis was conducted by further adjusting for the average hierarchical condition category (HCC) risk score of beneficiaries in the logistic regression model. The HCC risk score is a measure developed by Centers for Medicare & Medicaid Services as a risk score to predict beneficiaries’ future healthcare cost based on their characteristics that include diagnosis of acute or chronic conditions and institutional status; validation of HCC risk score revealed a predictive to actual ratio of 0.966 for cardiovascular disorders.25 The average HCC risk score is used as a proxy for the comorbidities of patients served by each clinician.26 A two-sided p<0.05 was considered to be statistically significant. These analyses were performed by using SAS V.9.4 (SAS Institute, Cary, North Carolina, USA).

In addition to logistic regression analysis, a geospatial analysis was conducted to further examine potential geographical variations in prescription patterns of oral anticoagulants in the USA. First, the number of clinicians who prescribed DOAC only or warfarin only was divided by the number of clinicians prescribing warfarin+DOAC, to compute the raw prescriber ratio at each zip code level. Clinicians whose zip code was not found in the 2019 Topologically Integrated Geographic Encoding and Referencing database were removed from the geospatial analysis (n=4553 from 333 zip codes, <2%). The raw prescriber ratio was then standardised27 to account for variations in specialty and gender of clinicians in each zip code. Indirect standardisation was used because of the small number of physicians at the zip code level (median=6). A Besag-York-Mollié model28 was then applied to spatially smooth the observed DOAC adoption at the county level. Model fitting was conducted using the integrated nested Laplace approximation method29 implemented in the R-INLA package.30 Lastly, the standardised prescriber ratios (SPRs) were visualised for all counties with at least one prescribing clinician. An SPR of 1 indicates the national average of SPR of DOAC only (or warfarin only) prescribers versus warfarin+DOAC prescribers, whereas deviations from 1 indicate hot spots (SPR>1; there were more DOAC only (or warfarin only) prescribers relative to warfarin+DOAC prescribers after standardisation) or cold spots (SPR<1; there were less DOAC only (or warfarin only) prescribers relative to warfarin+DOAC prescribers after standardisation). Mapping was conducted in ArcGIS V.10.4 (ESRI, Redlands, California, USA).

Results

Descriptive characteristics of clinicians

Among 232 665 clinicians who prescribed oral anticoagulants for Medicare beneficiaries in 2020, 7.9% only prescribed warfarin, 42.5% only prescribed DOAC and 49.6% prescribed both warfarin and DOAC. Among prescribers with warfarin only or warfarin+DOAC, about one in five was from rural areas, by contrast, among prescribers with DOAC only, about 1 in 10 was from rural areas. Differences were also found among these three groups in terms of service specialty, gender and US census region (all p<0.0001, table 1). For example, there was a higher percentage of advanced practice clinicians among those who only prescribed warfarin. There was a higher percentage of female clinicians among those who only prescribed warfarin. Also, there was a higher percentage of clinicians from the Midwest who were only prescribed warfarin.

Table 1

Characteristics of prescribers by prescribing patterns

Associations between urban–rural status and prescribing patterns of oral anticoagulants

Results on associations between urban–rural status and prescribing patterns of oral anticoagulants, adjusting for gender, specialty and US census region, are presented in table 2. Compared with clinicians from urban regions, clinicians from rural regions were more likely to prescribe warfarin only (adjusted OR=1.335, 95% CI=(1.281 to 1.391)); they were also more likely to prescribe DOAC only (adjusted OR=2.052, 95% CI=(1.999 to 2.106)). Further adjusting for the average HCC risk score of beneficiaries revealed similar results (adjusted OR=1.280, 95% CI=(1.227 to 1.335) for warfarin only vs warfarin+DOAC; adjusted OR=1.837, 95% CI=(1.789 to 1.886) for DOAC only vs warfarin+DOAC).

Table 2

Associations between urban–rural status and prescription patterns of oral anticoagulants

Standardised prescriber ratio

Figure 1 illustrates the SPR of DOAC only versus warfarin+DOAC prescribers. A diverse pattern was observed. Specifically, most southern and southeastern states, California, King County and Spokane County in Washington had the highest SPR as shown in red on the map; indicating clinicians from these places were more likely to prescribe DOAC only than warfarin+DOAC, after accounting for specialty and gender of clinicians. By contrast, Minnesota, Iowa and adjacent counties in nearby states had the lowest SPR of DOAC only versus warfarin+DOAC prescribers in the country as shown in blue as cold spots on the map.

Figure 1

The estimated standardised prescriber ratio (SPR) of DOAC only prescribers versus warfarin+DOAC prescribers. DOAC, direct oral anticoagulant.

Figure 2 illustrates the SPR of warfarin only versus warfarin+DOAC prescribers. The San Francisco Bay Area in California, most counties in Washington and Minnesota (such as Seattle and Twin Cities metropolitan areas and adjacent counties), eastern counties in Arizona and western counties in New Mexico, as well as the District of Columbia and adjacent counties, had the highest SPR as shown in red on the map; indicating clinicians from these places were more likely to prescribe warfarin only than warfarin+DOAC, after accounting for specialty and gender of clinicians. By contrast, states from the east coast of the country generally had the lowest SPR of warfarin only versus warfarin+DOAC prescribers, as indicated by cold spots on the map.

Figure 2

The estimated standardised prescriber ratio (SPR) of warfarin only prescribers versus warfarin+DOAC prescribers. DOAC, direct oral anticoagulant.

Discussion

This study found that among clinicians who prescribed oral anticoagulants, nearly 92% of them prescribed at least one type of DOAC. There were significant urban–rural differences in clinicians’ prescribing pattern, specifically, rural clinicians were more likely to be DOAC only prescribers or warfarin only prescribers, compared with clinicians from urban areas. Geospatial analysis revealed several metropolitan areas had the highest SPR of warfarin only prescribers versus warfarin+DOAC prescribers, whereas Minnesota and Iowa generally had the lowest SPR of DOAC only prescribers versus warfarin+DOAC prescribers.

Previous studies have shown a steady increase in share of DOAC among oral anticoagulants claims in the Medicare population.15 16 For example, it was 31% in 201515 and 57% in 2018.16 Results from the present study indicated further increase in 2020, at 72% (online supplemental table 1). The increase in DOAC shares may be largely driven by the decreased percentages of clinicians who prescribed warfarin as the only oral anticoagulant for Medicare beneficiaries. In 2013, 59% of Medicare service providers who prescribed oral anticoagulants only prescribed warfarin,16 by contrast, it was 7.9% in 2020.

Accumulating evidence revealed that geographical characteristics of clinicians are associated with their prescribing pattern; for example, urban–rural differences have been reported for prescription of postoperative opiods24 or long-term opiods.31 The present study found that clinicians from rural regions were more likely to prescribe DOAC only and warfarin only, when compared with clinicians from urban regions; in another word, urban clinicians were more likely to be warfarin+DOAC prescribers. While exact reasons for such differences warrant further studies, one potential explanation could be related to a greater heterogeneity in clinical characteristics of patients who were cared for by urban clinicians. The SD of the average HCC risk score from patients was 0.71 for urban clinicians and 0.48 for rural clinicians in the study (online supplemental table 2), indicating greater variations in patients’ clinical characteristics for urban clinicians. Such heterogeneity may increase the likelihood of using warfarin in some cases and DOAC in other cases, leading to a higher percentage of warfarin+DOAC prescribers among urban clinicians.

Previous studies using patient-level data on anticoagulant use patterns also revealed differences between rural and urban regions in both the USA and other countries. For example, a study in the USA indicated patients with atrial fibrillation living in rural areas were less likely to use DOAC.19 Similarly, a regional study in Spain also revealed patients with non-valvular atrial fibrillation living in rural areas were less likely to receive DOAC.32 By contrast, Bungard et al33 reported patterns of anticoagulant therapy for 695 patients with acute venous thromboembolism from six urban and three rural hospitals in Canada and found those patients in rural hospitals had a higher rate of DOAC use. Although these results may not be directly compared due to different study populations and different health insurance policies from different countries, they highlight the need for increased awareness of geographical disparities in the accessibilities of DOAC.

While DOAC may be the preferred oral anticoagulant in many clinical conditions, it does not mean warfarin does not have any place in clinical practice. The superior affordability of warfarin is a clear advantage for accessibility. For example, the cost per standardised 30-day fills was US$7.29 for warfarin and US$436.93 for DOAC in the study (online supplemental table 3); this suggested a substantial difference in upfront pharmacy cost. In fact, the cost of DOAC has been cited as one of the primary barriers to DOAC adoption.10 Nonetheless, survey results on prescription drug affordability among Medicare beneficiaries in 2019 revealed no significant urban–rural differences in percentages of patients with affordability problems or percentages of patients who did not get prescription needed due to cost.34 Moreover, cost-effectiveness analysis of data from published clinical trials indicated DOAC are more cost-effective than warfarin.35 Real-world data in patients receiving DOAC or warfarin for atrial fibrillation among those who enrolled in both Medicare and Veterans Affairs Healthcare System also indicated patients receiving DOAC had 42% lower average expenditure of 3-year medical cost, due to lower downstream cost following DOAC use.36 These indicate the upfront cost difference between warfarin and DOAC may not be considered the only factor when patients or providers make decisions.

To our knowledge, this is the first study that reported geographic heterogeneity of DOAC adoption in clinical practice in the USA using geospatial analysis. The geospatial analysis results complement findings on urban–rural differences observed from logistic regression analysis that assessed average differences at the national level and offered a high level of granularity into geographical variations. For example, clinicians from southeastern states were more likely to prescribe DOAC only. DOACs have been approved for various indications such as stroke prevention in atrial fibrillation, treatment and prevention of deep vein thrombosis and pulmonary embolism, prevention of thromboembolism.1 While county-level hospitalisation rate data for deep vein thrombosis and pulmonary embolism was not available, county-level hospitalisation rates for stroke and atrial fibrillation in Medicare beneficiaries37 revealed higher rates in southeastern regions in the USA. Therefore, this may have partly contributed to a higher DOAC adoption rate in these regions. Nonetheless, it does not explain the reasons for certain cold spots such as Minnesota and Iowa. Reasons for these cold spots are unknown and warrant future research; however, results from this study identified geographical regions which had the potential for increased DOAC adoption, either through clinician education for increased awareness and knowledge or through changes in healthcare policy. Future studies may focus on these cold spots and identify effective strategies to increase DOAC adoption.

There are several limitations in the study. First, like previous studies that examined clinicians’ prescription pattern,15 16 24 31 38 39 the study focused on clinician-level data. Although proxy was used to account for comorbidities of patients in the sensitivity analysis, other aggregated clinical data was not available, as with certain clinician characteristics such as years of clinical experiences; thus, there may be residual confounding. Second, it is not known whether and how patients may be involved in making any therapeutic decisions on the type of oral anticoagulants they receive; future studies on physician–patient interaction would be critical considering the increased focus on patient-centred care in clinical practice. Third, attitude on DOAC and how this affects clinicians’ prescribing practice was not known; data from clinician surveys may offer further insights on challenges in adoption of DOAC in clinical practice. Fourth, the study focused on Medicare beneficiaries, as such, results may not be generalisable to other populations such as those covered by private insurance plans. Fifth, it was unknown whether patients had Original Medicare Plan or Medicare Advantage Plan as both plans have different requirements related to choosing healthcare providers or referral for specialists; information on this, if available, would further delineate urban–rural differences in prescribing behaviours. Lastly, the start of the COVID-19 pandemic in 2020 may have changed clinicians’ prescribing patterns as DOAC use without the need for international normalised ratio monitoring requires less direct contact with patients; moreover, COVID-19 may also have changed patients’ care-seeking behaviours due to restrictions on mobility and access to care. Therefore, findings from the current study may not be representative of a prescription pattern of oral anticoagulants before the pandemic and after the pandemic.

Conclusions

Using the latest data from the Medicare Provider Utilisation and Payment Public Use File, the present study revealed urban–rural differences and geographical variations in DOAC use in the USA. Healthcare policy-makers and healthcare practitioners should be aware of gaps between clinical guidelines and real-world prescribing pattens and help address barriers to accessibility of DOAC for patients in need.

Data availability statement

Data are available in a public, open access repository. Data used in the study are publicly available at https://data.cms.gov/provider-summary-by-type-of-service/medicare-part-d-prescribers.

Ethics statements

Patient consent for publication

Ethics approval

As the present study is a secondary analysis of publicly available data, it was exempt from IRB review.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Contributors JZ, DL and YZ contributed to study design and results interpretation. DL and YZ performed the statistical analysis and wrote the first draft of the manuscript. JZ, DL and YZ contributed to manuscript revision, read and approved the submitted version. YZ is the guarantor.

  • Funding This work was supported by Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (JZ). Grant number: N/A.

  • Map disclaimer The inclusion of any map (including the depiction of any boundaries therein), or of any geographical or locational reference, does not imply the expression of any opinion whatsoever on the part of BMJ concerning the legal status of any country, territory, jurisdiction or area or of its authorities. Any such expression remains solely that of the relevant source and is not endorsed by BMJ. Maps are provided without any warranty of any kind, either express or implied.

  • Competing interests YZ is an employee of Wayzek Science. JZ and DL have nothing to declare.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.