Comparative Effectiveness of Rivaroxaban, Apixaban, and Warfarin in Atrial Fibrillation Patients With Polypharmacy

Background and Purpose: Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown. Methods: We used Medicare administrative data to evaluate patients with new atrial fibrillation diagnosis from 2015 to 2017, who initiated an oral anticoagulant within 90 days of diagnosis. Patients taking ≤3, 4 to 8, or ≥9 other prescription medications were categorized as having low, moderate, or high polypharmacy, respectively. Within polypharmacy categories, patients receiving apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or warfarin were matched using a 3-way propensity score matching. Study outcomes included ischemic stroke, bleeding, and all-cause mortality. Results: The study cohort included 6985 patients using apixaban, 3838 using rivaroxaban, and 6639 using warfarin. In the propensity-matched cohorts there was no difference in risk of ischemic stroke between the 3 drugs in patients with low and moderate polypharmacy. However, among patients with high polypharmacy, the risk of ischemic stroke was higher with apixaban compared with warfarin (adjusted hazard ratio 2.34 [95% CI, 1.01–5.42]; P =0.05) and similar to rivaroxaban (adjusted hazard ratio, 1.38 [95% CI, 0.67–2.84]; P =0.4). There was no difference in risk of death between the 3 drugs in patients with low and moderate polypharmacy, but apixaban was associated with a higher risk of death compared with rivaroxaban (adjusted hazard ratio, 2.03 [95% CI, 1.01–4.08]; P =0.05) in the high polypharmacy group. Apixaban had lower bleeding risk compared with warfarin in the low polypharmacy group (adjusted hazard ratio, 0.54 [95% CI, 0.32–0.90]; P =0.02), but there was no difference in bleeding between the 3 drugs in the moderate and high polypharmacy groups. Conclusions: Our study suggests that among patients with significant polypharmacy (>8 drugs), there may be a higher stroke and mortality risk with apixaban compared with warfarin and rivaroxaban. However, differences were of borderline significance.

Download Full-text

Risk of ischemic stroke in patients with acute myocardial infarction and new atrial fibrillation: a nationwide analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.0514 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L Fauchier ◽

A Bisson ◽

A Bodin ◽

J Herbert ◽

T Genet ◽

...

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Acute Myocardial Infarction ◽

Ischemic Stroke ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Risk Of Death ◽

Increased Risk ◽

History Of

Abstract Background In patients with acute myocardial infarction (AMI), history of atrial fibrillation (AF) and new onset AF during the early phase may be associated with a worse prognosis. Whether both conditions are associated with a similar risk of stroke and should be similarly managed is a matter of debate. Methods Based on the administrative hospital-discharge database, we collected information for all patients treated with AMI between 2010 and 2019 in France. The adverse outcomes were investigated during follow-up. Results Among 797,212 patients with STEMI or NSTEMI, 146,922 (18.4%) had history of AF, and 11,824 (1.5%) had new AF diagnosed between day 1 and day 30 after AMI. Patients with new AF were older and had more comorbidities than those with no AF but were younger and had less comorbidities than those with history of AF. Both groups with history of AF or new AF had less frequent STEMI and anterior MI, less frequent use of percutaneous coronary intervention but more frequent HF at the acute phase than patients with no AF. During follow-up (mean [SD] 1.8 [2.4] years, median [interquartile range] 0.7 [0.1–3.1] years), 163,845 deaths and 20,168 ischemic strokes were recorded. Using Cox multivariable analysis, compared to patients with no AF, history of AF was associated with a higher risk of death during follow-up (adjusted hazard ratio HR 1.06 95% CI 1.05–1.08) while this was not the case for patients with new AF (adjusted HR 0.98 95% CI 0.95–1.02). By contrast, both history of AF and new AF were associated with a higher risk of ischemic stroke during follow-up compared to patients with no AF: adjusted hazard ratio HR 1.29 95% CI 1.25–1.34 for history of AF, adjusted HR 1.72 95% CI 1.59–1.85 for new AF. New AF was associated with a higher risk of ischemic stroke than history of AF (adjusted HR 1.38 95% CI 1.27–1.49). Conclusion In a large and systematic nationwide analysis, AF first recorded in the first 30 days after AMI was associated with an increased risk of ischemic stroke. Specific management should be considered in order to improve outcomes in these patients after AMI. Funding Acknowledgement Type of funding source: None

Download Full-text

Abstract 140: Comparison of Major Complication of Oral Anticoagulants in Non-Valvular Atrial Fibrillation: Systematic Review and Meta-Analyses

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.140 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Hong Seok Lee

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Gi Bleeding ◽

Ischemic Stroke Risk ◽

Meta Analyses

Background: Oral anticoagulants known as a novel oral anticoagulant have been used for the management of non -valvular atrial fibrillation. There was no enough study regarding the efficacy and safety of three major new oral anticoagulants. We assessed major three oral anticoagulants in terms of major bleeding complication and stroke prevention by meta-analyses studies comparing those drugs. Method: Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2016). RevMan and ITC software were used for direct comparisons, respectively. Results: Apixaban (N=6020), versus dabigatran(N=12038), apixaban versus rivaroxaban(N=8503) and rivaroxaban versus dabigatran were analyzed directly. There was significantly higher major bleeding risks in apixaban compared to dabigatran (both 110mg and 150mg) after adjusting baseline bleeding risk (Relative risk 3.41, 95% confidence interval(2.61 to 4.47) in 110mg, (5.62, 4.83 to 6.54) in 150mg. Intracranial bleeding risk in apixaban was significantly higher than in dabigatran (10.5, 6.10 to18.01). However, apixaban had less GI bleeding risk compared to dabigatran (0.80 , 0.65 to 0.98) and also had less ischemic stroke risk (0.31,0.22 to 0.42). Rivaroxaban showed higher major bleeding risk than dabigatran 110mg (2.34 , 1.81 to 3.03), however, Rivaroxaban had less bleeding risk compared to dabigatran 150mg (0.41, 0.35 to 0.46). Dabigatran 110mg and 150mg had less GI bleeding risk compared to rivaroxaban (0.31 , 0.24 to 0.39) and (0.23,0.17 to 0.29) respectively. Ischemic stroke risk was also decreased in dabigatran110mg (0.46, 0.38 to 0.57). and 150mg (0.66 ,0.52 to 0.83). Conclusion: Observed oral anticoagulants were associated with various complications. Overall, apixaban had higher intracranial bleeding risk than dabigatran. The highest GI bleeding risk in rivaroxaban compared to apixaban and dabigatran. Ischemic stroke risk was the highest in dabigatran. In conclusion, we may use those oral anticoagulant based on risks rates, however, a larger study with longer follow-up is needed to corroborate findings.

Download Full-text

Role of Biological Markers for Cerebral Bleeding Risk STRATification in Patients with Atrial Fibrillation on Oral Anticoagulants for Primary or Secondary Prevention of Ischemic Stroke (Strat-AF Study): Study Design and Methodology

Medicina ◽

10.3390/medicina55100626 ◽

2019 ◽

Vol 55 (10) ◽

pp. 626 ◽

Cited By ~ 3

Author(s):

Anna Poggesi ◽

Carmen Barbato ◽

Francesco Galmozzi ◽

Eleonora Camilleri ◽

Francesca Cesari ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Biological Markers ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Circulating Biomarkers ◽

Cerebral Mri

Background and Objectives: In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. Cerebral small vessel disease (SVD) represents the pathologic substrate for primary intracerebral hemorrhage and ischemic stroke. We hypothesize that biological markers—both circulating and imaging-based—and their possible interaction, might improve the prediction of bleeding risk in AF patients under treatment with any type of oral anticoagulant. Materials and Methods: The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with AF, aged 65 years or older, and with no contraindications to magnetic resonance imaging (MRI), referring to Center of Thrombosis outpatient clinic of our University Hospital for the management of oral anticoagulation therapy. Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral MRI, and circulating biomarkers assessment at baseline and after 18 months. The main outcome is SVD progression—particularly microbleeds—as a selective surrogate marker of hemorrhagic complication. Stroke occurrence (ischemic or hemorrhagic) and the progression of functional, cognitive, and motor status will be evaluated as secondary outcomes. Circulating biomarkers may further improve predictive potentials. Results: Starting from September 2017, 194 patients (mean age 78.1 ± 6.7, range 65–97; 61% males) were enrolled. The type of AF was paroxysmal in 93 patients (48%), and persistent or permanent in the remaining patients. Concerning the type of oral anticoagulant, 57 patients (29%) were on vitamin K antagonists, and 137 (71%) were on direct oral anticoagulants. Follow-up clinical evaluation and brain MRI are ongoing. Conclusions: The Strat-AF study may be an essential step towards the exploration of the role of a combined clinical biomarker or multiple biomarker models in predicting stroke risk in AF, and might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting stroke risk and improvement in clinical outcomes in a cost-effective fashion.

Download Full-text

Association Between High-Sensitivity Cardiac Troponin and Risk of Stroke in 96 702 Individuals

Stroke ◽

10.1161/strokeaha.119.028323 ◽

2020 ◽

Vol 51 (4) ◽

pp. 1085-1093 ◽

Cited By ~ 6

Author(s):

Leonie H.A. Broersen ◽

Helena Stengl ◽

Christian H. Nolte ◽

Dirk Westermann ◽

Matthias Endres ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

General Population ◽

Cardiac Troponin ◽

Meta Analysis ◽

High Sensitivity ◽

Hazard Ratio ◽

Risk Of Bias ◽

Adjusted Hazard Ratio ◽

Previous Stroke

Background and Purpose— Our study aim was to estimate risk of incident stroke based on levels of hs-cTn (high-sensitivity cardiac troponin), a specific biomarker indicating myocardial injury, in the general population, patients with atrial fibrillation, and patients with previous stroke. Methods— Embase, PubMed, and Web of Science were searched until March 14, 2019 to identify relevant articles. Randomized controlled trials and cohort studies assessing the risk of incident stroke based on hs-cTn were eligible. Pooled adjusted hazard ratios including 95% CI were calculated using a random-effects model due to study heterogeneity per population, coding of hs-cTn (categorical/continuous data), per hs-cTn subunit (T or I), for low risk of bias, and for all-cause and ischemic stroke separately. Results— We included 17 articles with 96 702 participants. In studies conducted in the general population (n=12; 77 780 participants), the pooled adjusted hazard ratio for incident stroke was 1.25 (CI, 1.10–1.40) for high versus low hs-cTn (as defined by included studies) during an average follow-up of 1 to 20 years (median 10). When categorical data were used, this was increased to 1.58 (CI, 1.26–1.90). The results were robust when accounting for stroke classification (all-cause stroke/ischemic stroke), hs-cTn subunit, risk of bias, and coding of hs-cTn. In patients with atrial fibrillation (4 studies; 18 725 participants), the pooled adjusted hazard ratio for incident stroke was 1.95 (CI, 1.29–2.62) for high versus low hs-cTn. Due to lack of data (one study, 197 participants), no meta-analysis could be performed in patients with previous stroke. Conclusions— This meta-analysis suggests that hs-cTn can be regarded as a risk marker for incident stroke, with different effect size in different subgroups. More research about the association between hs-cTn and incident stroke in high-risk populations is needed, especially in patients with history of ischemic stroke.

Download Full-text

Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.119.028118 ◽

2020 ◽

Vol 51 (3) ◽

pp. 883-891 ◽

Cited By ~ 2

Author(s):

Tadataka Mizoguchi ◽

Kanta Tanaka ◽

Kazunori Toyoda ◽

Sohei Yoshimura ◽

Ryo Itabashi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Hazard Ratio ◽

Interquartile Range ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Ischemic Attack

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Download Full-text

Oral anticoagulants usage in Japanese patients aged 18–74 years with non-valvular atrial fibrillation: a retrospective analysis based on insurance claims data

Family Practice ◽

10.1093/fampra/cmz016 ◽

2019 ◽

Vol 36 (6) ◽

pp. 685-692 ◽

Cited By ~ 2

Author(s):

Ayako Ohshima ◽

Toshihiro Koyama ◽

Aiko Ogawa ◽

Yoshito Zamami ◽

Hiroyoshi Y Tanaka ◽

...

Keyword(s):

Atrial Fibrillation ◽

Claims Data ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Japanese Patients ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Insurance Claims ◽

Systemic Embolism ◽

Insurance Claims Data

Abstract Background Oral anticoagulants use has increased rapidly, internationally. Here we look at risks and benefits, based on Japanese data, of therapy with low risk non-valvular atrial fibrillation patients. Objectives Using a health insurance claims data set we assessed: (i) oral anticoagulants usage in Japan, and (ii) efficacy and safety of dabigatran compared with warfarin, in Japanese patients with non-valvular atrial fibrillation, aged 18–74 years. Methods We identified 4380 non-valvular atrial fibrillation patients treated with anticoagulants between 1 January 2005, and 28 February 2014, and estimated the adjusted hazard ratio for stroke or systemic embolism, and any hemorrhagic event (Cox proportional hazards regression model with stabilized inverse probability treatment weighting). Results The data included 101 989 anticoagulant prescriptions for 4380 patients, of which direct oral anticoagulants increased to 40.0% of the total by the end of the study. After applying exclusion criteria, 1536 new non-valvular atrial fibrillation patients were identified, including 1071 treated with warfarin and 465 with dabigatran. Mean ages were 56.11 ± 9.70 years for warfarin, and 55.80 ± 9.65 years for dabigatran. The adjusted hazard ratio (95% confidence interval), comparing dabigatran with warfarin, was 0.48 (0.25–0.91) for stroke or systemic embolism, and 0.91 (0.60–1.39) for any hemorrhage including intracranial and gastrointestinal. Conclusions Number of patients prescribed direct oral anticoagulants steadily increased, and incidence of all-cause bleeding related to dabigatran was similar to warfarin, in our study population of younger non-valvular atrial fibrillation patients. Dabigatran, compared with warfarin, generally reduced risk of all-cause stroke and systemic embolism.

Download Full-text

Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation

Blood Advances ◽

10.1182/bloodadvances.2017010694 ◽

2018 ◽

Vol 2 (3) ◽

pp. 200-209 ◽

Cited By ~ 51

Author(s):

Surbhi Shah ◽

Faye L. Norby ◽

Yvonne H. Datta ◽

Pamela L. Lutsey ◽

Richard F. MacLehose ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Cancer Patients ◽

Comparative Effectiveness ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Patients With Cancer ◽

Key Points

Key Points In AF and cancer patients, rate of bleeding is lower with apixaban, similar in dabigatran and rivaroxaban users, compared to warfarin users. Ischemic stroke rates did not differ among anticoagulant users. Incident VTE risk was lower in all DOAC compared with warfarin users.

Download Full-text

Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Prior Gastrointestinal Bleeding

Stroke ◽

10.1161/strokeaha.120.030761 ◽

2021 ◽

Author(s):

Soonil Kwon ◽

So-Ryoung Lee ◽

Eue-Keun Choi ◽

Euijae Lee ◽

Jin-Hyung Jung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Gastrointestinal Bleeding ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Hazard Ratio ◽

Composite Outcome ◽

Inverse Probability ◽

Secondary Outcomes

Background and Purpose: Limited data support the benefits of non–vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB. Methods: Oral anticoagulant–naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes. Results: A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA 2 DS 2 -VASc score, 3.7). Lower risks of ischemic stroke, major bleeding, and the composite outcome were associated with NOAC use than with warfarin use (weighted hazard ratio, 0.608 [95% CI, 0.543–0.680]; hazard ratio, 0.731 [95% CI, 0.642–0.832]; and hazard ratio, 0.661 [95% CI, 0.606–0.721], respectively). For all secondary outcomes, NOACs showed greater risk reductions compared with warfarin. Conclusions: NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.

Download Full-text

Bleeding Risk of Direct Oral Anticoagulants in Patients With Heart Failure And Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.007230 ◽

2021 ◽

Vol 14 (2) ◽

Author(s):

Cynthia A. Jackevicius ◽

Lingyun Lu ◽

Zunera Ghaznavi ◽

Alberta L. Warner

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Hazard Ratio ◽

Patients With Heart Failure

Background: Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin. Methods: We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting. Results: Total bleeding (hazard ratio, 0.62 [95% CI, 0.56–0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40–0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71–0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing. Conclusions: DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.

Download Full-text

Abstract 169: The Role Of Clinical Prediction Factors On Anticoagulant Selection In Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.7.suppl_1.169 ◽

2014 ◽

Vol 7 (suppl_1) ◽

Author(s):

Julie Lauffenburger

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Patient Characteristics ◽

Treatment Selection ◽

Risk Scores ◽

Treatment Benefit ◽

Risk Treatment

Background: Atrial fibrillation (AF) often benefits from the use of anticoagulants for prevention of stroke or systemic embolism. While novel oral anticoagulants have emerged as possible alternatives to warfarin, it is unknown how treatment selection is determined in practice with clinical guidelines still evolving. This study examined whether and to what extent anticoagulant selection has been driven by clinical predictions of stroke risk (treatment benefit) and bleeding risk (treatment harm) in real-world practice in the US. Methods: A nationwide database of commercial and Medicare Part D supplement claims from 2009-2011 was used to extract a cohort of non-valvular AF patients who were newly-initiating therapy after dabigatran availability in Oct 2010. Patients were excluded if they had claims associated with a reversible AF condition. Risk scores of ischemic stroke (CHADS2 and CHA2DS2-VASc) and bleeding (ATRIA) were used to examine associations with either warfarin or dabigatran use, calculated via claims in the outpatient pharmaceutical, inpatient medical, outpatient, and provider claims files. Baseline demographic and clinical characteristics were also measured as covariates, including concomitant diseases and medications. Multivariable log-binomial regression models assessed the association between each risk score and anticoagulant use, adjusting for the measured covariates. C-statistics were also used to examine the variation in treatment selection explained by inclusion of the risk scores. Results: In total, 37,401 patients were identified with 31% initiating dabigatran. New users of dabigatran were more likely to be younger, male, and have comorbidities. Patients at intermediate stroke risk (CHADS2 or CHA2DS2-VASc =1) were equally likely to receive warfarin and dabigatran (RR, 95% CI: 0.98, 0.93-1.02), while selection for warfarin was significantly associated with high ischemic stroke risk (CHADS2 or CHA2DS2-VASc ≥2) (RR, 95% CI: 0.87, 0.83-0.92). New users of dabigatran were significantly less likely to have high bleeding risk (ATRIA≥5) versus warfarin (RR, 95%: 0.70, 0.66-0.74). The c-statistic of the base model, which included the other measured covariates, was only marginally increased with the addition of any of the risk scores. Conclusions: Despite controlling for other patient characteristics, bleeding risk was strongly associated with the selection of a specific anticoagulant. However, the extent of selection explained by predictions of treatment harm was minimal. Providers appear to base anticoagulant selection on factors other than predictions of treatment benefit, which has implications for studying the anticoagulants’ comparative effectiveness.

Download Full-text