International Journal of Cardiology 192 (2015) 1–2
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
The impact of inpatient rivaroxaban versus warfarin on hospital-based outcomes when used for stroke prevention in patients with anticoagulant naïve, new-onset nonvalvular atrial fibrillation Caitlyn Hurley a, Shurui Dai b, Diana M. Sobieraj b,⁎ a b
Pharmacy Services, Hartford Hospital, 80 Seymour St., Hartford, CT 06102, USA University of Connecticut School of Pharmacy, Department of Pharmacy Practice, 69 N. Eagleville Rd. Unit 3092, Storrs, CT 06269, USA
a r t i c l e
i n f o
Article history: Received 22 April 2015 Accepted 30 April 2015 Available online 1 May 2015 Keywords: Atrial fibrillation Stroke prevention Anticoagulant
Target specific oral anticoagulants (TSOACs) are alternatives to warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Stroke prophylaxis in NVAF does not require immediate therapeutic anticoagulation; however, delaying discharge in patients treated with warfarin to achieve a therapeutic international normalized ratio (INR) may prolong hospital length of stay (LOS) compared to use of a TSOAC. We aimed to evaluate patients hospitalized for new-onset, NVAF that were initiated on either rivaroxaban or warfarin for stroke prevention and hospital-based outcomes. This retrospective observational study included patients admitted to the hospital for new-onset, NVAF or atrial flutter that were anticoagulant naïve, had a CHA2DS2-VASc score of at least 2, and were initiated on rivaroxaban or warfarin during the first 17 months in which rivaroxaban was on formulary. Patients were excluded if they were hospitalized for observation, if anticoagulation was not continued through discharge or was switched to another oral anticoagulant during the hospital stay. Patients were identified for eligibility through International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for AF and atrial flutter. Inclusion criteria were confirmed through medical record review, which was also utilized to collect demographic data and the individual criteria used to calculate a CHA2DS2-VASc score and an ATRIA score for each patient [1,2]. In-hospital major bleeding, minor bleeding and the need for transfusion of blood or
⁎ Corresponding author. E-mail addresses: [email protected] (C. Hurley), [email protected] (S. Dai), [email protected] (D.M. Sobieraj).
http://dx.doi.org/10.1016/j.ijcard.2015.04.240 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
blood products were determined using ICD-9 codes. This study was approved by the Institutional Review Board with a waiver of informed consent. Patient demographics and baseline characteristics were compared between patients treated with rivaroxaban and those treated with warfarin using the chi-square or Fisher's exact test. To evaluate the impact of rivaroxaban versus warfarin on hospital LOS and total hospital costs, multivariate general linear models were assembled. Covariates with a p-value ≤0.20 were considered for inclusion in the final models along with the anticoagulant therapy and a propensity score that was calculated for each patient using age, gender, race and the health conditions found in the CHA2DS2-VASc and ATRIA tools. Final results, reported as days for LOS and dollars for hospital costs each with accompanying 95% confidence intervals, were adjusted for the anticoagulant therapy, propensity score, age, race, history of heart failure and history of hypertension. Frequency of in-hospital major bleeding, minor bleeding, and use of blood or blood products was compared between anticoagulant groups using the Fisher's exact test. INR control in patients treated with warfarin was descriptively reported. A p-value of b0.05 was considered statistically significant for final analyses. All statistical analyses were conducted with IBM SPSS Statistics for Windows® Version 22.0 (IBM Corp., Armonk, NY 2013). Of the 89 included patients, most were Caucasian (83%), female (55%) and aged 65 years or older (74%) (Table 1). The majority of patients had a CHA2DS2-VASc score between two and four and the most common contributing health conditions were heart failure and hypertension. The majority of patients (65%) had a low-risk (b 1%) of major bleeding as defined by an ATRIA score of three or less. In the final adjusted model, initiating anticoagulation with rivaroxaban compared to warfarin in this patient population was associated with a significantly shorter LOS [− 2.14 days (− 3.70 to − 0.59)] and lower hospital costs [−$4783.88 (−8976.49 to −591.27)]. In-hospital safety events were rare in both groups (Table 2). In the 64 patients treated with warfarin, an average of 6.98 (3.86) INRs was drawn per patient. Five patients (7.8%) had an INR of four or higher during their hospital stay. Thirty-six patients (56.2%) achieved an INR ≥2 prior to discharge in an average of 4.39 (2.70) days. Few patients (n = 9, 14%) achieved two consecutive therapeutic INRs prior to discharge. Results of this study suggest that initiating rivaroxaban for stroke prevention in patients hospitalized for new-onset, NVAF is associated with a shorter LOS and reduced hospital costs. In-hospital bleeding
2
C. Hurley et al. / International Journal of Cardiology 192 (2015) 1–2
Table 1 Baseline characteristics.
Age, years b65 65 to 74 ≥75 Male Race White Black Other CHA2DS2-VASc score 2 3 4 5 6 7 8 ATRIA score ≤3 4 ≥5 History of heart failure History of HTN History of stroke or TIA History of vascular disease History of diabetes mellitus History of hemorrhage Renal disease Anemia
Table 2 In-hospital safety outcomes. Rivaroxaban (n = 25) n (%)
Warfarin (n = 64) n (%)
6 (24.0) 11 (44.0) 8 (32.0) 9 (36.0)
17 (26.6) 20 (31.2) 27 (42.2) 31 (48.4)
18 (72.0) 4 (16.0) 3 (12.0)
56 (87.5) 4 (6.3) 4 (6.3)
5 (20.0) 3 (12.0) 9 (36.0) 7 (28.0) 1 (4.0) 0 (0) 0 (0)
7 (10.9) 17 (26.6) 17 (26.6) 16 (25) 5 (10.9) 1 (1.6) 1 (1.6)
20 (80.0) 2 (8.0) 3 (12.0) 12 (48.0) 24 (96.0) 0 (0) 8 (32.0) 10 (40.0) 2 (8.0) 0 (0) 5 (20.0)
38 (59.4) 10 (15.6) 16 (25.0) 28 (43.8) 57 (89) 10 (15.6) 26 (40.6) 22 (34.3) 4 (6.8) 5 (7.8) 25 (39.0)
Major in-hospital bleed, n (%) Minor in-hospital bleed, n (%) In-hospital blood or blood product transfusion, n (%)
Rivaroxaban (n = 25)
Warfarin (n = 64)
p-Value
1 (4.0) 1 (4.0) 1 (4.0)
1 (1.6) 2 (3.1) 0 (0)
0.485 1.00 0.281
Observational studies with methods to control for confounding are an important addition to the literature describing the real-world utilization of therapy which can differ from the controlled environment of a clinical trial [7]. However, these results should be considered within the context of its limitations. As with all observational studies, only the variables that are known can be accounted for and therefore there is always the risk of bias. However, we used robust methods to adjust for confounding including propensity scores and multivariate regression analyses. A larger sample size would allow for the adjustment of additional confounding variables. Reliance of ICD-9 codes for in-hospital events is subject to misclassification bias. Our results reflect the short-term early stage of anticoagulation in this population; since AF is a chronic condition with a long-term need for anticoagulation, clinicians should consider these results in the context of long term data. Conflict of interest None.
AbbreviationsHTN hypertension TIA transient ischemic attack
Acknowledgments
was rare in both groups. About half of the patients treated with warfarin achieved a therapeutic INR prior to discharge. Results are applicable to a patient population that is consistent with national practice guideline recommendations, including those with a CHA2DS2-VASc score of two or greater [3]. Studied patients also had a relatively low risk of bleeding as reflected by the ATRIA scores that were calculated, which is important in applying these results to a broader patient population in terms of safety and bleeding events. In hospitals where delaying discharge to obtain a therapeutic INR is more common than what was found in this study, the difference in LOS and costs may be even greater. Prior claim-based observational studies suggest that initiating rivaroxaban or dabigatran compared to warfarin in patients with AF categorized as new-onset, anticoagulant naive, is associated with a significantly shorter LOS (0.70 to 1.16 days) and reduced hospital costs ($2300 to $2700) [4–6]. Our study supports these findings although differs most notably by the access we had to medical records and our ability to confirm clinical characteristics of patients as well as obtain data regarding in-hospital safety outcomes and for those treated with warfarin, measures of INR control. These strengths add to the validity of our results and to the totality of the evidence supporting TSOAC use in patients hospitalized for NVAF.
References
None. This research was unfunded.
[1] G.Y. Lip, R. Nieuwlaat, R. Pisters, et al., Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation, Chest 137 (2010) 263–272. [2] M.C. Fang, A.S. Go, Y. Chang, L.H. Borowsky, N.K. Pomernacki, N. Udaltsova, D.E. Singer, A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study, J. Am. Coll. Cardiol. 58 (2011) 395–401. [3] C.T. January, L.S. Wann, J.S. Alpert, et al., AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society, J. Am. Coll. Cardiol. S0735-1097 (14) (2014) 01740–01749. [4] F. Laliberté, D. Pilon, M.K. Raut, et al., Hospital length of stay: is rivaroxaban associated with shorter inpatient stay compared to warfarin among patients with non-valvular atrial fibrillation? Curr. Med. Res. Opin. 30 (2014) 645–653. [5] F. Laliberté, D. Pilon, M.K. Raut, et al., Is rivaroxaban associated with lower inpatient costs compared to warfarin among patients with non-valvular atrial fibrillation? Curr. Med. Res. Opin. 1–10 (2014). [6] E. Fonseca, D. Walker, G. Hess, Dabigatran etexilate is associated with a shorter hospital stay and lower hospital costs compared to warfarin in treatment-naïve, newly diagnosed nonvalvular atrial fibrillation patients, Circ. Cardiovasc. Qual. Outcomes 6 (Suppl. 1) (2013). [7] L.P. Garrison, P.J. Neumann, P. Erickson, et al., Using real‐world data for coverage and payment decisions: the ISPOR real‐world data task force report, Value Health 10 (2007) 326–335.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
The impact of inpatient rivaroxaban versus warfarin on hospital-based outcomes when used for stroke prevention in patients with anticoagulant naïve, new-onset nonvalvular atrial fibrillation Caitlyn Hurley a, Shurui Dai b, Diana M. Sobieraj b,⁎ a b
Pharmacy Services, Hartford Hospital, 80 Seymour St., Hartford, CT 06102, USA University of Connecticut School of Pharmacy, Department of Pharmacy Practice, 69 N. Eagleville Rd. Unit 3092, Storrs, CT 06269, USA
a r t i c l e
i n f o
Article history: Received 22 April 2015 Accepted 30 April 2015 Available online 1 May 2015 Keywords: Atrial fibrillation Stroke prevention Anticoagulant
Target specific oral anticoagulants (TSOACs) are alternatives to warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Stroke prophylaxis in NVAF does not require immediate therapeutic anticoagulation; however, delaying discharge in patients treated with warfarin to achieve a therapeutic international normalized ratio (INR) may prolong hospital length of stay (LOS) compared to use of a TSOAC. We aimed to evaluate patients hospitalized for new-onset, NVAF that were initiated on either rivaroxaban or warfarin for stroke prevention and hospital-based outcomes. This retrospective observational study included patients admitted to the hospital for new-onset, NVAF or atrial flutter that were anticoagulant naïve, had a CHA2DS2-VASc score of at least 2, and were initiated on rivaroxaban or warfarin during the first 17 months in which rivaroxaban was on formulary. Patients were excluded if they were hospitalized for observation, if anticoagulation was not continued through discharge or was switched to another oral anticoagulant during the hospital stay. Patients were identified for eligibility through International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for AF and atrial flutter. Inclusion criteria were confirmed through medical record review, which was also utilized to collect demographic data and the individual criteria used to calculate a CHA2DS2-VASc score and an ATRIA score for each patient [1,2]. In-hospital major bleeding, minor bleeding and the need for transfusion of blood or
⁎ Corresponding author. E-mail addresses: [email protected] (C. Hurley), [email protected] (S. Dai), [email protected] (D.M. Sobieraj).
http://dx.doi.org/10.1016/j.ijcard.2015.04.240 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
blood products were determined using ICD-9 codes. This study was approved by the Institutional Review Board with a waiver of informed consent. Patient demographics and baseline characteristics were compared between patients treated with rivaroxaban and those treated with warfarin using the chi-square or Fisher's exact test. To evaluate the impact of rivaroxaban versus warfarin on hospital LOS and total hospital costs, multivariate general linear models were assembled. Covariates with a p-value ≤0.20 were considered for inclusion in the final models along with the anticoagulant therapy and a propensity score that was calculated for each patient using age, gender, race and the health conditions found in the CHA2DS2-VASc and ATRIA tools. Final results, reported as days for LOS and dollars for hospital costs each with accompanying 95% confidence intervals, were adjusted for the anticoagulant therapy, propensity score, age, race, history of heart failure and history of hypertension. Frequency of in-hospital major bleeding, minor bleeding, and use of blood or blood products was compared between anticoagulant groups using the Fisher's exact test. INR control in patients treated with warfarin was descriptively reported. A p-value of b0.05 was considered statistically significant for final analyses. All statistical analyses were conducted with IBM SPSS Statistics for Windows® Version 22.0 (IBM Corp., Armonk, NY 2013). Of the 89 included patients, most were Caucasian (83%), female (55%) and aged 65 years or older (74%) (Table 1). The majority of patients had a CHA2DS2-VASc score between two and four and the most common contributing health conditions were heart failure and hypertension. The majority of patients (65%) had a low-risk (b 1%) of major bleeding as defined by an ATRIA score of three or less. In the final adjusted model, initiating anticoagulation with rivaroxaban compared to warfarin in this patient population was associated with a significantly shorter LOS [− 2.14 days (− 3.70 to − 0.59)] and lower hospital costs [−$4783.88 (−8976.49 to −591.27)]. In-hospital safety events were rare in both groups (Table 2). In the 64 patients treated with warfarin, an average of 6.98 (3.86) INRs was drawn per patient. Five patients (7.8%) had an INR of four or higher during their hospital stay. Thirty-six patients (56.2%) achieved an INR ≥2 prior to discharge in an average of 4.39 (2.70) days. Few patients (n = 9, 14%) achieved two consecutive therapeutic INRs prior to discharge. Results of this study suggest that initiating rivaroxaban for stroke prevention in patients hospitalized for new-onset, NVAF is associated with a shorter LOS and reduced hospital costs. In-hospital bleeding
2
C. Hurley et al. / International Journal of Cardiology 192 (2015) 1–2
Table 1 Baseline characteristics.
Age, years b65 65 to 74 ≥75 Male Race White Black Other CHA2DS2-VASc score 2 3 4 5 6 7 8 ATRIA score ≤3 4 ≥5 History of heart failure History of HTN History of stroke or TIA History of vascular disease History of diabetes mellitus History of hemorrhage Renal disease Anemia
Table 2 In-hospital safety outcomes. Rivaroxaban (n = 25) n (%)
Warfarin (n = 64) n (%)
6 (24.0) 11 (44.0) 8 (32.0) 9 (36.0)
17 (26.6) 20 (31.2) 27 (42.2) 31 (48.4)
18 (72.0) 4 (16.0) 3 (12.0)
56 (87.5) 4 (6.3) 4 (6.3)
5 (20.0) 3 (12.0) 9 (36.0) 7 (28.0) 1 (4.0) 0 (0) 0 (0)
7 (10.9) 17 (26.6) 17 (26.6) 16 (25) 5 (10.9) 1 (1.6) 1 (1.6)
20 (80.0) 2 (8.0) 3 (12.0) 12 (48.0) 24 (96.0) 0 (0) 8 (32.0) 10 (40.0) 2 (8.0) 0 (0) 5 (20.0)
38 (59.4) 10 (15.6) 16 (25.0) 28 (43.8) 57 (89) 10 (15.6) 26 (40.6) 22 (34.3) 4 (6.8) 5 (7.8) 25 (39.0)
Major in-hospital bleed, n (%) Minor in-hospital bleed, n (%) In-hospital blood or blood product transfusion, n (%)
Rivaroxaban (n = 25)
Warfarin (n = 64)
p-Value
1 (4.0) 1 (4.0) 1 (4.0)
1 (1.6) 2 (3.1) 0 (0)
0.485 1.00 0.281
Observational studies with methods to control for confounding are an important addition to the literature describing the real-world utilization of therapy which can differ from the controlled environment of a clinical trial [7]. However, these results should be considered within the context of its limitations. As with all observational studies, only the variables that are known can be accounted for and therefore there is always the risk of bias. However, we used robust methods to adjust for confounding including propensity scores and multivariate regression analyses. A larger sample size would allow for the adjustment of additional confounding variables. Reliance of ICD-9 codes for in-hospital events is subject to misclassification bias. Our results reflect the short-term early stage of anticoagulation in this population; since AF is a chronic condition with a long-term need for anticoagulation, clinicians should consider these results in the context of long term data. Conflict of interest None.
AbbreviationsHTN hypertension TIA transient ischemic attack
Acknowledgments
was rare in both groups. About half of the patients treated with warfarin achieved a therapeutic INR prior to discharge. Results are applicable to a patient population that is consistent with national practice guideline recommendations, including those with a CHA2DS2-VASc score of two or greater [3]. Studied patients also had a relatively low risk of bleeding as reflected by the ATRIA scores that were calculated, which is important in applying these results to a broader patient population in terms of safety and bleeding events. In hospitals where delaying discharge to obtain a therapeutic INR is more common than what was found in this study, the difference in LOS and costs may be even greater. Prior claim-based observational studies suggest that initiating rivaroxaban or dabigatran compared to warfarin in patients with AF categorized as new-onset, anticoagulant naive, is associated with a significantly shorter LOS (0.70 to 1.16 days) and reduced hospital costs ($2300 to $2700) [4–6]. Our study supports these findings although differs most notably by the access we had to medical records and our ability to confirm clinical characteristics of patients as well as obtain data regarding in-hospital safety outcomes and for those treated with warfarin, measures of INR control. These strengths add to the validity of our results and to the totality of the evidence supporting TSOAC use in patients hospitalized for NVAF.
References
None. This research was unfunded.
[1] G.Y. Lip, R. Nieuwlaat, R. Pisters, et al., Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation, Chest 137 (2010) 263–272. [2] M.C. Fang, A.S. Go, Y. Chang, L.H. Borowsky, N.K. Pomernacki, N. Udaltsova, D.E. Singer, A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study, J. Am. Coll. Cardiol. 58 (2011) 395–401. [3] C.T. January, L.S. Wann, J.S. Alpert, et al., AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society, J. Am. Coll. Cardiol. S0735-1097 (14) (2014) 01740–01749. [4] F. Laliberté, D. Pilon, M.K. Raut, et al., Hospital length of stay: is rivaroxaban associated with shorter inpatient stay compared to warfarin among patients with non-valvular atrial fibrillation? Curr. Med. Res. Opin. 30 (2014) 645–653. [5] F. Laliberté, D. Pilon, M.K. Raut, et al., Is rivaroxaban associated with lower inpatient costs compared to warfarin among patients with non-valvular atrial fibrillation? Curr. Med. Res. Opin. 1–10 (2014). [6] E. Fonseca, D. Walker, G. Hess, Dabigatran etexilate is associated with a shorter hospital stay and lower hospital costs compared to warfarin in treatment-naïve, newly diagnosed nonvalvular atrial fibrillation patients, Circ. Cardiovasc. Qual. Outcomes 6 (Suppl. 1) (2013). [7] L.P. Garrison, P.J. Neumann, P. Erickson, et al., Using real‐world data for coverage and payment decisions: the ISPOR real‐world data task force report, Value Health 10 (2007) 326–335.
