Abstract
Background
Although controversial, several prior studies have suggested that oral anticoagulants (OACs) are underused in the US atrial fibrillation (AF) population. Appropriate use of OACs is essential because they significantly reduce the risk of stroke in those with AF. In the >2 million Americans with AF, OACs are recommended when the risk of stroke is moderate or high but not when the risk of stroke is low. To quantify trends and guideline adherence, we evaluated OAC use (either warfarin or dabigatran) in a 10-year period in patients with new AF in the Veterans Health Administration.
Methods
New AF was defined as at least 2 clinical encounters documenting AF within 120 days of each other and no previous AF diagnosis (N = 297,611). Congestive Heart Failure, Hypertension, Age >75, Diabetes, and Stroke (CHADS2) scores were determined using age and diagnoses of hypertension, diabetes, heart failure, and stroke or transient ischemic attack during the 12 months before AF diagnosis. Receipt of an OAC within 90 days of a new diagnosis of AF was evaluated using VA pharmacy data.
Results
Overall, initiation of an OAC fell from 51.3% in 2002 to 43.1% in 2011. For patients with CHADS2 score of 0, 1, 2, 3, 4, and 5–6, the proportions of patients prescribed an OAC showed a relative decrease of 26%, 23%, 14%, 12%, 9%, and 13%, respectively (P >.001). Clopidogrel use was stable at 10% of the AF population.
Conclusions
Among US veterans with new AF and additional risk factors for stroke, only about half receive OAC, and the proportion is declining.
Although controversial, several prior studies have suggested that oral anticoagulants (OACs) are underused in the US atrial fibrillation (AF) population.1–5 Appropriate use of OACs is essential because they significantly reduce the risk of stroke in those with AF.6,7 In the >2 million Americans with AF, OACs—either warfarin or one of several non–vitamin K antagonist oral anticoagulants—are recommended when the risk of stroke is moderate or high but not when the risk of stroke is low. In 2001, Gage et al8 combined previously conflicting guidelines9,10 into the Congestive Heart Failure, Hypertension, Age >75, Diabetes, and Stroke (CHADS2) score to evaluate stroke risk and to guide the selection of antithrombotic therapy for patients with nonvalvular AF. Rates of stroke among patients with a CHADS2 of 0 are low (<2.0 per 100 patient-years) but rise with greater CHADS2 scores. Over the decade following the introduction of CHADS2, a number of medical organizations adopted its use into their guidelines and began suggesting an OAC in patients with CHADS2 scores of at least 1.11–14 Regardless, prior studies have suggested discordance between recommendations and utilization of OACs: they found that 20%−55% of patients with a CHADS2 ≥2 did not receive OAC therapy, whereas 40%−53% of those with a CHADS2 score of 0 received OAC therapy.1–5 These studies did have limitations. They examined populations that were modest in size, susceptible to possible selection biases, or constrained by financial or access-to-care barriers.
We use 10 years of data from the Veteran Health Administration (VHA) in efforts to mitigate limitations in prior studies. The VHA serves >5 million veterans annually, providing a national data set that exceeds the scope of previous studies. Furthermore, the VHA helps veterans overcome financial and logistical barriers to care faced by other Americans. Veterans in the VHA pay little for many medications.
The objective of this study was to quantify trends and evaluate guideline adherence with OACs in veterans with newly diagnosed AF over a 10-year period. We hypothesized that, over time, use of OACs among patients with a CHADS2 of ≥2 would increase, whereas the use of OACs among patients with a low risk would decrease or remain steady.
Methods
Patients
Patients with a new episode of AF from October 1, 2001, through September 30, 2011, were identified in VA Outpatient Care Files and Inpatient Treatment Files using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code 427.31. There were 406,168 new AF episodes, defined as at least 2 encounters for AF within 120 days of each other and no AF-related encounters during the 12 months prior. To ensure complete diagnostic information during the prior 12 months, 94,561 patients who were not receiving care in VHA for ≥12 months before the AF episode were excluded. Furthermore, 13% of patients had >1 eligible episode during the entirety of the study period (ie, AF diagnosis with no prior AF diagnosis in previous 12 months). For these patients, the first of the eligible episodes was selected. This left 297,611 episodes during the 10-year period.
Variable definition
We searched VA Decision Support System National Pharmacy Extracts for prescriptions for OACs filled by VA pharmacies. OACs included warfarin and dabigatran, the only OACs on the VHA formulary during this time period. In addition, prescriptions for the antiplatelet agent clopidogrel were identified. We did not identify aspirin use because of its availability without a prescription. Drugs were identified by the VA identification number (IEN), which corresponds to the National Drug Code for generic drug names. We defined the use of each medication type as a binary variable indicating any use within 90 days of the first date of the AF diagnosis.
Diagnoses of hypertension, diabetes, heart failure, and prior stroke or transient ischemic attack reported during the 12 months preceding the initial AF date were identified and used to calculate a CHADS2 for each patient, as has been done in prior studies.15 Additional diagnoses that are known bleeding risk factors and might contraindicate anticoagulation were also identified, including prior bleeding episodes, alcohol abuse, renal disease, or liver disease.16
Statistical analysis
Unadjusted trends in the use of antithrombotics were evaluated using the Cochran-Armitage test for trend. Multivariable logistic regression was used to examine associations while controlling for risk factors that impact bleeding risk or potentially contraindicate anticoagulation. We used SAS version 9.3 (SAS Institute, Inc, Cary, NC) for all analyses. This study was approved by the Institutional Review Board of the Iowa City VA Medical Center and University of Iowa. This work was supported by awards from Agency for Healthcare Research and Quality, the Health Services Research and Development Service of the Department of Veterans Affairs, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.
Results
The number of patients with new AF diagnoses increased, with new diagnoses increasing from 51,133 during the first year of observation (2002–2003) to 68,774 during the final year of observation (2010–2011). The median (interquartile range) CHADS2 remained unchanged at 2 (1–3). During the study period, the proportion of patients age ≥81 years increased from 23% to 30%, and those with renal disease increased from 7.9% to 14.1% (Table I).
Table I.
Characteristics of patients with new AF episodes during FY2002–2003 and FY2010–2011
| 2002–2003 | 2010–2011 | |
|---|---|---|
| No. of new AF episodes | 51133 | 68774 |
| Age category (y) | ||
| <50 | 980 (1.9%) | 1343 (2.0%) |
| 51–60 | 4794 (9.4%) | 6293 (9.2%) |
| 61–70 | 10659 (20.9%) | 21115 (30.7%) |
| 71–80 | 23009 (45.0%) | 19705 (28.7%) |
| ≥81 | 11691 (22.9%) | 20318 (29.5%) |
| Female, n (%) | 848 (1.7%) | 1284 (1.9%) |
| Race | ||
| White, n (%) | 31963 (86.3%) | 50974 (85.0%) |
| Black, n (%) | 3556 (9.6%) | 5704 (9.5%) |
| Other nonwhite, n (%) | 1525 (4.1%) | 3256 (5.5%) |
| Total nonmissing | 37044 | 59934 |
| Missing race (not reflected in percentages) | 14089 | 8840 |
| CHADS2 score | ||
| 0 | 4848 (9.5%) | 5791 (8.4%) |
| 1 | 14203 (27.8%) | 17642 (25.6%) |
| 2 | 17281 (33.8%) | 24666 (35.9%) |
| 3 | 9818 (19.2%) | 13840 (20.1%) |
| 4 | 3606 (7.1%) | 4975 (7.2%) |
| 5–6 | 1377 (2.7%) | 1860 (2.7%) |
| Bleeding risk factors in 12 m prior | ||
| Alcohol abuse | 1710 (3.3%) | 4169 (6.1%) |
| Major bleed (cranial, GI hemorrhage) | 2814 (5.5%) | 3801 (5.5%) |
| Minor bleed (other site) | 3935 (7.7%) | 5208 (7.6%) |
| Renal disease | 4046 (7.9%) | 9666 (14.1%) |
| Liver disease | 1005 (2.0%) | 1911 (2.8%) |
All differences are statistically significant (P >.01). GI, Gastrointestinal.
In aggregate, 47% of patients received an OAC within 90 days of AF. In addition, 8.5% to 11.4% received clopidogrel, either with or without an OAC. Dabigatran, approved by the US Food and Drug Administration in October 2010, accounted for only 0.7% of patients on antithrombotic therapy in 2010–2011. There was an absolute reduction in use of OACs over time from 51% during 2002–2003 to 43% in 2010–2011 (relative reduction 16%) (Table II). This reduction occurred for all CHADS2 scores, but the decrease differed significantly by CHADS2, with the largest reduction in patients with low CHADS2 scores (Table III). By 2011, the proportions of patients prescribed warfarin or dabigatran within 90 days of AF showed a relative decrease of 26%, 23%, 14%, 12%, 9%, and 13% for patients with CHADS2 score of 0, 1, 2, 3, 4, and 5–6, respectively (P > 0.001) (Figure 1). After controlling for bleeding risk factors, the relative reductions were 29%, 23%, 11%, 8%, 5%, and 9% for patients with CHADS2 of 0, 1, 2, 3, 4, and 5–6, respectively.
Table II.
Percentage of patients who received prescription antithrombotics within 90 days of new AF episode and percentage change in use from 2001 to 2011
| 2002–2003 (n = 51133) | 2004–2005 (n = 56510) | 2006–2007 (n = 58134) | 2008–2009 (n = 63060) | 2010–2011 (n = 68774) | % Change unadjusted | % Change risk adjusted | |
|---|---|---|---|---|---|---|---|
| Warfarin* | 51.3% | 49.8% | 49.0% | 46.0% | 43.1% | −16.0% | −15.8% |
| Clopidogrel | 8.5% | 11.4% | 10.2% | 8.9% | 9.7% | +15.0% | +13.2% |
Includes 240 patients who took dabigatran in FY2010–2011.
Table III.
Percentage of patients who received prescription antithrombotics within 90 days of new AF by CHADS2 and year and percentage change in use from 2001 to 2011
| 2002–2003 (n = 51133) | 2004–2005 (n = 56510) | 2006–2007 (n = 58134) | 2008–2009 (n = 63060) | 2010–2011 (n = 68774) | % Change unadjusted | %Change risk adjusted | |
|---|---|---|---|---|---|---|---|
| Anticoagultion by year and CHADS2 (warfarin, dabigatran) | |||||||
| CHADS2: 0 | 46.9% | 45.7% | 45.6% | 43.1% | 34.5% | −26.4% | −29.2% |
| 1 | 50.7% | 49.2% | 48.5% | 44.9% | 39.2% | −22.7% | −22.6% |
| 2 | 51.4% | 50.0% | 48.9% | 45.5% | 44.4% | −13.6% | −11.2% |
| 3 | 53.4% | 51.1% | 50.9% | 48.0% | 46.8% | −12.4% | −8.3% |
| 4 | 52.3% | 51.8% | 49.8% | 48.4% | 47.7% | −8.8% | −4.6% |
| 5 − 6 | 55.3% | 50.7% | 50.6% | 49.6% | 48.1%* | −13.0% | −9.1% |
| Clopidogrel by year and CHADS2 | |||||||
| CHADS2: 0 | 5.4% | 6.6% | 5.6% | 5.0% | 4.7% | −13.0% | +4.0% |
| 1 | 6.0% | 8.9% | 7.8% | 7.1% | 7.6% | +26.7% | +23.3% |
| 2 | 7.6% | 10.3% | 9.6% | 8.6% | 9.4% | +23.7% | +21.5% |
| 3 | 10.5% | 13.6% | 12.4% | 10.6% | 11.9% | +13.3% | +13.1% |
| 4 | 15.7% | 19.4% | 15.9% | 13.3% | 14.8% | −5.7% | −7.7% |
| 5–6 | 23.4% | 26.3% | 21.5% | 16.4% | 19.5% | −16.7% | −19.1% |
Figure 1.
Proportion of patients with new AF episodes receiving warfarin or dabigatran within 90 days, by CHADS2 and year of episode.
The decrease in OAC use was partially offset by a modest increase in the use of clopidogrel. From 2002 through 2011, the overall use of clopidogrel increased from 8.5% to 9.7% (Table II). When stratified by CHADS2 scores, clopidogrel use increased for patients with a CHADS2 of ≤3 and decreased for patients with a CHADS2 of ≥4. This pattern was seen both in unadjusted analysis (Figure 2) and in analysis adjusted for bleeding risk factors (Table III).
Figure 2.
Proportion of patients with new AF episodes receiving clopidogrel within 90 days, by CHADS2 score and year of episode.
Discussion
This study showed a general decline in the rates of initiating OAC therapy from 2002 to 2011 among veterans with new AF. Patients with low stroke risk had significant decreases in OAC use, as hypothesized, but more than one-third of patients with a CHADS2 score of 0 still received an OAC in the final years of the study. Surprisingly, patients with higher risks for stroke also had significant declines in use of OAC therapy. This decline is concerning because patients with AF who fail to receive recommended OAC have high rates of preventable stroke.7
The introduction of the CHADS2 score in 2001 provided a simple clinical prediction tool for assessing stroke risk for patients with AF.8 Coupled with the widespread dissemination of guidelines that recommend antithrombotic therapy stratified by CHADS2 scores, we expected rates of OAC use to decrease in patients with low stroke risk and increase in those with a greater risk. Instead, we found that OAC use decreased across all CHADS2 scores. Underuse became more common by the end of the 10-year period. During this time, use of clopidogrel remained relatively stable. These patterns persisted even after controlling for contraindications to anticoagulation.
The decreased rates of OAC use become more profound in light of more recent guidelines of the American College of Chest Physicians, American Heart Association/American College of Cardiology/Heart Rhythm Society, European Society of Cardiology, and Canadian Cardiovascular Society. All advocate OACs for AF patients with multiple stroke risk factors, but many have broadened the recommended use of OACs to patients who would have been deemed low risk before 2010.17–20 The Canadian Cardiovascular Society and American College of Chest Physicians have recommended OAC use for patients with CHADS2 of ≥1. In patients with a CHADS2 of 1, antiplatelet therapy is only recommended if patients cannot tolerate or refuse anticoagulation or have a reasonable alternative as indicated by risk-benefit ratio.18,19 Furthermore, dual antiplatelet therapy with clopidogrel and aspirin is more effective than aspirin alone in preventing strokes.21 However, dual antiplatelet therapy is less effective than warfarin and is infrequently recommended because of its elevated overall risk of hemorrhage.22
The surprising decline in OACs among patients with a CHADS2 score of ≥1 may have several explanations. First, reasons for failure to prescribe an OAC include patient refusal as well as physician reluctance to prescribe an OAC due to concern about bleeding, fall risk, potential medication interactions, or compliance.19,23 This concern may have become magnified over the study period, as our population saw an increase in octogenarians as well as concurrent increase in renal disease (7.9% to 14.1%) (Table I). Together, these changes may have increased the propensity for bleeding. However, the common concern of the risk of hemorrhage can be diminished with one of the many risk-stratification tools developed to help balance the risks of hemorrhage with benefits of anticoagulation.16,24,25 Second, some physicians may be prescribing antiplatelet therapy instead of an OAC. However, the minimal increase in clopidogrel use does not fully account for the decrease in OAC use. Furthermore, use of aspirin alone or with clopidogrel in patients with a CHADS2 score of ≥1 would still depart from AF guidelines. Even among patients with AF and recent percutaneous coronary interventions, guidelines still recommend OAC therapy in combination with antiplatelet therapy (ie, aspirin and clopidogrel or clopidogrel alone).13,20 Third, dabigatran was approved by the Food and Drug Administration in October 2010 but was not available in VHA until 8 months later. It is possible that patients with alternative access to prescription medications may have obtained dabigatran through private sector pharmacies. However, the introduction of dabigatran would only impact the last 2 years of our data, and the overall decrease we found was observed in all years. Other non–vitamin K antagonist oral anticoagulants (eg, rivaroxaban, apixaban) were not available during the study period. Likewise, some VHA patients may also receive health services, including pharmaceuticals, in the private sector. With Medicare Part D starting in 2006, the use of pharmacies outside VHA may have increased. Analysis of previously acquired CMS data for VHA patients revealed that 14% of patients with a first AF diagnosis during FY2010–2011 were enrolled in Medicare Part D during the year of their first AF episode. Moreover, receipt of an OAC through a VA pharmacy was slightly lower for veterans enrolled in CMS Part D compared with other patients in 2010–2011 (41% vs 44% receiving an OAC within 90 days of AF), suggesting that prescriptions received outside the VA may partly explain the observed decrease in oral anticoagulant use. Finally, throughout the last decade, VHA has maintained anticoagulation clinics nationwide. Patients receiving warfarin through VHA are required to participate in periodic monitoring through anticoagulation clinics to continue receiving OACs. As use of anticoagulation clinics increased, it is possible that patients for whom regular monitoring through VHA facilities was difficult either obtained medications outside VHA or stopped OACs use.
This study has limitations that must be acknowledged. First, the accuracy of some ICD-9-CM diagnoses may be questionable.26 Nevertheless, prior studies using VHA administrative data have established algorithms based on ICD-9 codes for calculating the CHADS2 score.27 Second, we were not able to capture aspirin use (because it is sold over the counter). However, it is unlikely that aspirin use increased enough to explain the decrease in prescription OACs. Third, this study used CHADS2 scores instead of the more recent Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke, Vascular Disease (CHA2DS2-VASc),28 which further reflects the increased risk of stroke in patients with vascular disease, female gender, and age 65 to 74 years. Since its introduction in 2012, CHA2DS2-VASc has been incorporated into some clinical guidelines because it may better estimate stroke risk among patients with a CHADS2 of 0.17,20 However, because our study period ended in 2011, this score was not available to guide physician decisions during our study period. Moreover, the benefit of anticoagulation in patients with a CHA2DS2-VASc >0 but a CHADS2 of 0 is not clear. For example, female patients >65 years old would have a CHA2DS2-VASc of 1 but a CHADS2 score of 0. These patients have little or no net benefit from OAC.29,30 Regardless, a patient could have CHADS2 of 0 and higher CHA2DS2-VASc because of vascular disease, which would make the use of aspirin (possibly with clopidogrel) justified. Similarly, it is possible that some of the patients with a CHADS2 of 0 could have had another reason not identified in our analysis (eg, cardioversion) that would mandate OAC therapy.
Despite these minor limitations, we found a disappointing trend of decreasing rates of OAC therapy in AF patients who have significant stroke risk. The decreased rates of guideline adherence for OACs in the VHA are consistent with some, but not all, reports. Whereas several studies of have shown continued over- and underanticoagulation over the previous decade,1–5 some studies show improved adherence to guidelines.31 In the early 2000s, many European countries showed similar rates to other parts of the world.32–34 However, a recent Danish study showed treatment was guideline adherent at a rate of 75.7%.35 Taken together, these studies show opportunity to improve rates of guideline adherence at least when financial and logistic barriers are mitigated. Future studies will be needed to better understand the remaining discrepancies between current guidelines and actual use. Better understanding of these trends in the VHA, with its large cohort of elderly population, could help with the challenges of changing demographics as the Baby Boomer population ages.
Acknowledgements
This work was supported by a Mentored Career Enhancement Award in Patient Centered Outcomes Research for Mid-Career and Senior Investigators (K18) provided to Dr. Vaughan Sarrazin by the Agency for Healthcare Research and Quality, and by the Health Services Research and Development Service of the Department of Veterans Affairs. Dr Peter Cram is supported by a K24 award from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (AR062133). The authors do not have any conflicts of interest or financial relationships related to the content of this manuscript. The authors had full access to and take full responsibility for the integrity of the data. This manuscript is not under review elsewhere, and there is no prior publication of manuscript contents. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.
Footnotes
Appendix. Supplementary data
Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.ahj.2016.03.029.
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