1. Length of Hospital Stay for Bleeding Among Adults with Atrial Fibrillation Treated with Warfarin, Dabigatran, or Rivaroxaban
Blake Charlton MD1, Gboyega Adeboyeje MD2, Deborah Grady MD MPH1, John J Barron PharmD2, Jaekyu Shin PharmD3, Rita Redberg MD MSc1
1Dept. of Internal Medicine, UCSF, San Francisco, CA, 2HealthCore Inc., Wilmington, DE, 3Dept. of Clinical Pharmacy UCSF, San Francisco, CA.
Importance
Use of Novel Oral Anticoagulants (NOACs) to reduce embolic events in Atrial Fibrillation (AF) is increasing. However, little is known about the relative risks of medical complications associated with bleeding during NOAC therapy.
Objective
To compare length of stay for adults with AF who were hospitalized for bleeding after initiation of warfarin, dabigatran, or rivaroxaban.
Hypothesis
Because NOAC anticoagulation is irreversible, NOAC-related bleeding is likely more medically complicated & therefore associated with longer hospital stays.
Methods
We performed a retrospective, longitudinal cohort study using a US commercial claims database of ~38 million, 11/1/10 – 3/31/14.
Inclusion Criteria:
Adults with new AF initiating therapy on warfarin, dabigatran, or rivaroxaban.
Hospitalized for at least 1 day for bleeding.
Exclusion criteria:
Mechanical heart valve
Hypercoaguable syndrome (APLS, Factor V Leiden, etc)
Switched anticoagulant prior to bleeding event
Main outcome: hospital length of stay.
Secondary outcomes: ICU stay & length of ICU stay.
Statistical analysis: Propensity scores for adjustment of multivariate regression.
Subgroup analysis: CKD, HF, >7 comorbidities, >75yo, ICH, GIB, & restarting or discontinuing anticoagulation.
Results
After adjustment for baseline differences results:
Average total hospitalization: Warfarin 9.1 days, dabigatran 6.7 days, rivaroxaban 5.9 days.
Percent ICU stay: Warfarin 32.6%, dabigatran 33.0%, rivaroxaban 29.7%.
Average ICU stay: warfarin 9.0 days, dabigatran 6.7 days, rivaroxaban 7.1 days.
Limitations
Warfarin cohort older and frailer, however, large magnitude of differences make it unlikely that differences are purely the result of residual confounding.
Unable to capture transfusion data; therefore, it is possible that NOAC-related bleeding was resuscitated more aggressively leading to shorter stays.
Conclusions
Among adults with new AF admitted for bleeding after initiation of anticoagultion
Warfarin is associated with longer total hospitalizations & longer ICU stays compared to dabigatran & rivaroxaban.
Continuing anticoagulation & > 7 comorbidities demonstrate effect modification, increasing warfarin’s association with longer hospitalization.
In part, warfarin might prolong hospitalization because of difficulty titrating dose & accounting for drug-drug interactions among frail patients.
Therefore warfarin-associated bleeding may be more medically complex than treatment of dabigatran- or rivaroxaban-associated bleeding.
Subgroup analysis
Warfarin’s increased length of stay persists in subgroups with <75 years old, < 7 comorbidities, & those discontinuing anticoagulation.
Warfarin’s increased length of stay exaggerated in subgroups with > 7 comorbidities & those continuing anticoagulation.
No significant difference between dabigatran & rivaroxaban in subgroups with > 7 comorbidities, > 75 years old.
NOACs more likely to be discontinued; however, in subgroup of those who discontinued anticoagulation, warfarin still associated with longer hospitalization.
*Very few patients, further analysis needed.