P279 Standard dose of rivaroxaban in Asian patients with atrial fibrillation: 20ms vs.15mg? Off label dose reduction of rivaroxaban should be avoided

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
H K Jeong ◽  
J M Won ◽  
K H Lee ◽  
N S Yoon ◽  
H W Park ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Standard Dose ◽  
Comparable Efficacy ◽  
Systemic Embolism ◽  
Off Label ◽  
Safety Outcome ◽  
Asian Patients ◽  
Net Clinical Benefit

Abstract Background Rivaroxaban emerged as potential alternatives to warfarin for the prevention of thromboembolisim in patients with atrial fibrillation (AF). Because of the concern for the risk of major bleeding with rivaroxaban in Asian patients, off label rivaroxaban dose reduction to15mg is common in Asian real-world practice. We aimed to set standard rivaroxaban dose in Asian patients with AF by comparison between on-label rivaroxaban 20mg and off-label reduced rivaroxaban dose 15mg. Methods A total of 2,208 consecutive non-valvular AF patients were enrolled between 2011 and 2017. After propensity score matching, both warfarin (n = 804) and rivaroxaban group (n = 804) had comparable baseline characteristics. Rivaroxaban group was further divided into on-label rivaroxaban 20mg group (n = 390) and off-label reduced rivaroxaban 15mg group (n = 333). Efficacy outcome was stroke/systemic embolism. Safety outcome was major bleeding. Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism and major bleeding. Patients were followed upto one-year or until the first occurrence of any study outcomes. Results Both Rivaroxaban groups had comparable efficacy compared to warfarin. However, both on-label rivaroxaban 20mg (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.18-0.90, p = 0.026) and off-label reduced rivaroxaban 15mg (HR 0.37, 95% CI 0.16-0.88, p = 0.025) significantly reduced major bleeding. There were no differences in efficacy and safety outcomes between on-label rivaroxaban 20mg and off-label reduced rivaroxaban 15mg group. On-label rivaroxaban 20mg significantly reduced primary (HR 0.44, 95% CI 0.25-0.79, p = 0.006) and secondary (HR 0.51, 95% CI 0.27-0.96, p = 0.038) NCBs compared to warfarin. However, off-label reduced rivaroxaban 15mg did not reduce both primary and secondary NCBs. Conclusion Off-label rivaroxaban dose reduction to 15mg had no benefit compared to on-label rivaroxaban 20mg. Compared to warfarin, on-label rivaroxaban 20mg significantly improved primary and secondary NCBs, whereas off-label reduced rivaroxaban 15mg did not. Therefore, rivaroxaban 20mg is favorable as standard dose in Asian patients.

scholarly journals What is Standard Dose of Rivaroxaban in Elderly Asian Patients with Atrial Fibrillation: 20ms versus. 15mg?

2021 ◽  
Vol 27 ◽  
pp. 107602962110611
Author(s):  
Sung Soo Kim ◽  
Ki Hong Lee ◽  
Nam Sik Yoon ◽  
Hyung Wook Park ◽  
Jeong Gwan Cho
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Standard Dose ◽  
Comparable Efficacy ◽  
Systemic Embolism ◽  
Off Label ◽  
Korean Patients ◽  
Asian Patients

Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12–0.93) and secondary (HR 0.31, 95% CI: 0.10–0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

2021 ◽  
Author(s):  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Sang-Hyun Park ◽  
Jin-Hyung Jung ◽  
Kyung-Do Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Dose Reduction ◽  
Clinical Outcomes ◽  
Standard Dose ◽  
Composite Outcome ◽  
Claims Database ◽  
Off Label ◽  
Asian Patients ◽  
Hazard Ratios

Abstract Aims To compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with atrial fibrillation (AF). Methods and results Using the Korean nationwide claims database, we identified patients who were prescribed apixaban and did not fulfil the dose reduction criteria for apixaban between January 2015 and December 2017. A multivariable Cox hazard regression model was performed, and hazard ratios (HRs) for ischaemic stroke, major bleeding (MB), all-cause death, and composite outcome were analysed. Compared to patients prescribed on-label standard dose apixaban (n = 4194), patients prescribed off-label underdosed apixaban (n = 2890) showed a higher risk of ischaemic stroke [adjusted HR (aHR) 1.38, 95% confidence interval (CI) 1.06–1.81], all-cause death (aHR 1.19, 95% CI 1.01–1.39), and the composite outcome (aHR 1.17, 95% CI 1.03–1.34), but with no significant differences in MB between the two groups. Among the patients who did not meet any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischaemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% CI 1.25–2.73). Among the patients who met a single dose reduction criterion, off-label underdosed apixaban use was associated with a higher risk of all-cause death than on-label standard dose apixaban (aHR 1.32, 95% CI 1.07–1.64). Conclusion The off-label underdosed apixaban group showed higher risks of ischaemic stroke, all-cause death, and composite clinical outcomes than the on-label standard dose apixaban group, but both showed comparable risks of MB. Label adherence to apixaban dosing should be emphasized to achieve the best clinical outcomes for Asian patients with AF.

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
SR Lee ◽  
EK Choi ◽  
SH Park ◽  
JH Jung ◽  
KD Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Dose Reduction ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Off Label ◽  
Funding Sources ◽  
Asian Patients

Abstract Funding Acknowledgements Type of funding sources: None. Background In Asian patients with atrial fibrillation (AF), off-label underdosed prescriptions of direct oral anticoagulants (DOACs) are common Purpose We aimed to compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with AF. Methods Using the Korean nationwide claims database, we identified patients who prescribed apixaban and did not fulfill the dose reduction criteria of apixaban between January 2015 and December 2017. Multivariable Cox hazard regression model was performed and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and the composite clinical outcome were analyzed. Results Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) were associated with higher risks of ischemic stroke (adjusted HR [aHR] 1.38, 95% confidence interval [CI] 1.06-1.81), all-cause death (aHR 1.19, 95% CI 1.01-1.39) and the composite clinical outcome (aHR 1.17, 95% CI 1.03-1.34), but with no significant differences in MB between the two groups (Figure). In patients without any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% 1.25-2.73); however, in patients who had single dose reduction criteria (age ≥80 years, serum creatinine ≥1.5mg/dL, or bodyweight ≤60 kg), off-label underdosed apixaban use did not show a significant overall benefit in the composite clinical outcome compared with on-label standard dose apixaban, but was associated with a higher risk of all-cause death (aHR 1.32, 95% CI 1.07-1.64). Conclusion Off-label underdosed apixaban use was associated with higher risks of ischemic stroke, all-cause death, and composite clinical outcome and comparable risk of MB compared with on-label standard dose apixaban use. Label-adherence of apixaban dosing should be emphasized to achieve the best clinical outcome for Asian patients with non-valvular AF, especially in those without any dose reduction criteria. Abstract Figure.

scholarly journals Impacts of off-label dosing noacs on clinical outcomes in very elderly patients with atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Chao ◽  
Y.H Chan ◽  
G.Y.H Lip ◽  
S.A Chen
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Lower Risk ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
Very Elderly ◽  
Off Label ◽  
Funding Sources ◽  
Clinical Events

Abstract Background Studies about the comparisons of on-label and off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) regarding the risks of clinical outcomes among atrial fibrillation (AF) patients have been published. However, data among the very elderly AF patients were limited. In the present study, we aimed to investigate the impacts of inappropriate dosing of NOACs on clinical outcomes in AF patients aged ≥85 years of age. Methods We used medical data from a multi-center healthcare system in Taiwan enrolling 1,836 and 268 AF patients aged ≥85 years treated with NOACs and warfarin, respectively. Among 1,836 patients receiving NOACs, underdosing, overdosing and on-label dosing NOACs were prescribed in 248, 149 and 1439 patients, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding were compared between warfarin and NOACs in different dosing groups. Also, the risks of clinical events of underdosing and overdosing NOACs were comapred to on-labeling dosing. Results Compared to warfarin, underdosing NOACs were associated with a higher risk of IS/SE (aHR 2.39; p=0.048) without a lower risk of major bleeding; while overdosing NOACs were not associated with a lower risk of IS/SE (aHR 0.74, p=0.604) (Figure 1). Compared to on-label dosing NOACs, underdosing NOACs were associated with a higher risk of IS/SE, while the risk was not lower for overdoing NOACs (Figure 2). Conclusions Even for very elderly AF patients aged ≥85 years, NOACs should still be prescribed at the dosing following the criteria defined in clinical trials and guideline recommendations. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

Heart ◽  
2021 ◽  
pp. heartjnl-2020-318753
Author(s):  
Ole-Christian Walter Rutherford ◽  
Christian Jonasson ◽  
Waleed Ghanima ◽  
Fabian Söderdahl ◽  
Sigrun Halvorsen
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Sensitivity Analyses ◽  
World Population ◽  
Systemic Embolism ◽  
Reduced Dose

ObjectivesTo assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.MethodsWe identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.ResultsAmong 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.ConclusionIn this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

scholarly journals The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242922
Author(s):  
Oh Young Bang ◽  
Young Keun On ◽  
Myung-Yong Lee ◽  
Sung-Won Jang ◽  
Seongwook Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
Real World Data ◽  
Level Of Evidence ◽  
Warfarin Group ◽  
Asian Patients

Background Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice. Aims To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice. Methods Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea’s nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin. Results Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54–0.71; 0.60, 0.53–0.69; and 0.71, 0.56–0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51–0.66 and 0.75, 0.60–0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69–1.04), showed a significantly lower MB risk than warfarin. Conclusions Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.

P4769Optimal rivaroxaban dose in Asian patients with atrial fibrillation and normal or mildly impaired renal function

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E.-K Choi ◽  
S R Lee ◽  
K D Han ◽  
J H Jung ◽  
S Oh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Major Bleeding ◽  
Impaired Renal Function ◽  
Gi Bleeding ◽  
Nonsignificant Trend ◽  
Off Label ◽  
Asian Patients

Abstract Background Although rivaroxaban 15 mg was only given to patients with creatinine clearance (CrCl) <50mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with non-valvular atrial fibrillation (AF) regardless of renal function. There is a paucity of information regarding the clinical outcomes of rivaroxaban 15 mg compared to rivaroxaban 20 mg in patients with CrCl ≥50mL/min. This study aimed to examine the effectiveness and safety of two doses of rivaroxaban in Asian patients with AF and CrCl ≥50mL/min. Methods Using the Korean National Health Insurance Service database, patients with AF and normal or mildly impaired renal function (CrCl ≥50mL/min) and naïve to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: rivaroxaban 20 mg (R20) vs. warfarin (n=15,584), rivaroxaban 15 mg (R15) vs. warfarin (n=11,554), and R20 vs. R15 (n=10,392). Hazard ratios (HRs) for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results Among the pooled total study population, mean age was 66.9±10.9 years, 62.2% were male, mean CHA2DS2-VASc score was 3.16±1.79, and mean CrCl was 83.6±42.0 mL/min (median 78.4 mL/min, IQR 67.7–91.0 mL/min). A substantial proportion (42.6%) of patients with CrCl ≥50 mL/min were prescribed off-label R15 for stroke prevention in the Korean AF population. Compared to warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of ICH), and all-cause death (Figure). Overall, both R20 and R15 had better results for the composite clinical outcome compared to warfarin (HR: 0.617, 95% CI: 0.550–0.691 for R20, and HR: 0.759, 95% CI: 0.675–0.853 for R15). Compared to off-label R15, on-label R20 showed a nonsignificant trend toward lower risks of ischemic stroke, hospitalization for GI bleeding, hospitalization for major bleeding, and all-cause death. Overall, on-label R20 had better results for the composite clinical outcome compared to off-label R15 in patients with CrCl ≥50 mL/min (HR: 0.852, 95% CI: 0.735–0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. In patients with CrCl 50–60 mL/min, R20 showed a nonsignificant trend toward a higher risk of hospitalization for major bleeding compared to R15 (HR: 1.828, 95% CI 0.994–3.452). Conclusions Among Asians with AF and CrCl ≥50mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, ICH, major bleeding, and all-cause death without significantly increased risk of GI bleeding compared with warfarin. In patients with CrCl ≥50mL/min, on-label R20 showed better results for the composite clinical outcome compared to off-label R15.

P4767VTE-BLEED score predicts major bleeding in patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F A Klok ◽  
K G Chu ◽  
L Valerio ◽  
S J Van Der Wall ◽  
S Barco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
High Risk ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Bleeding Risk ◽  
Composite Outcome ◽  
Systemic Embolism ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Bleeding risk scores in atrial fibrillation (AF) are used to identify risk factors for bleeding but not to determine anticoagulant therapy since high bleeding risk strongly correlates to high risk of stroke. VTE-BLEED is a simple bleeding risk score (Klok FA Eur Respir J 2016) that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in AF. Aims To evaluate VTE-BLEED in AF and whether dabigatran dose reduction in VTE-BLEED high-risk patients would result in a lower incidence of MB and the composite endpoint of MB plus stroke/systemic embolism. Methods Assessment of VTE-BLEED in 18040 patients of the RE-LY trial (Connolly SJ NEJM 2009) that compared dabigatran (both 150mg BID and 110mg BID) to warfarin. The score was calibrated to fit the AF population. Hazard ratios (HR) were obtained for the VTE-BLEED high-risk patients randomized to dabigatran. The risk ratios for MB and the composite outcome of MB plus stroke/systemic embolism between dabigatran 150mg and 110mg were calculated for the VTE-BLEED high-risk group. Results The adapted VTE-BLEED score classified 4060 patients (22.5%) as high-risk. A high score indeed predicted MB in patients treated with dabigatran 150mg BID or 110mg BID, for HRs of 2.48 (95% CI 1.96–3.13) and 2.61 (95% CI 2.04–3.33), respectively. In VTE-BLEED high-risk patients, the risk ratio between the two dabigatran doses was 0.53 (95% CI 0.35–0.78) for MB and 0.55 (95% CI 0.38–0.79) for the composite outcome, both in favor of dabigatran 110mg BID (Figure 1). Compared to the current European label of dabigatran, application of VTE-BLEED to determine dabigatran dosing would result in a different dose for 21% of patients. Figure 1 Conclusions VTE-BLEED was validated for AF. Our data suggest that dabigatran dose reduction in VTE-BLEED bleed high-risk patients -in addition to targeting individual modifiable risk factors for bleeding- may lower the risk of MB and improve patient outcome. This finding could have important clinical implications but should be confirmed in future studies.

scholarly journals Off-Label Underdosing or Overdosing of Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaojuan Wu ◽  
Linyan Hu ◽  
Jinjin Liu ◽  
Qiuping Gu
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Off Label ◽  
Label Dose

Background: Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients.Methods: The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model (I2 ≤ 50%) or a random-effects model (I2 &gt; 50%).Results: A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02–1.16), and all-cause death (RR = 1.29, 95% CI 1.10–1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76–2.36), myocardial infarction (RR = 1.08, 95% CI 0.92–1.28), major bleeding (RR = 0.97, 95% CI 0.89–1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90–1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85–1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05–1.36), all-cause death (RR = 1.22, 95% CI 1.06–1.39), and major bleeding (RR = 1.33, 95% CI 1.16–1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99–1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75–1.30).Conclusion: Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.

P4752Apixaban 2.5 mg twice daily is effective and safe for patients with atrial fibrillation and combinations of advanced age, low body weight, and elevated creatinine: insights from ARISTOTLE

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Zeitouni ◽  
A Giczewska ◽  
R D Lopes ◽  
D Wojdyla ◽  
C Christersson ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Plasma Concentrations ◽  
Similar Efficacy ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Risk Patients ◽  
Elevated Creatinine ◽  
The Relationship

Abstract Background In ARISTOTLE, patients with atrial fibrillation and ≥2 dose-reduction criteria [age ≥80 years, weight ≤60 kg, and creatinine ≥1.5 mg/dL (133 μmol/L)] were randomized to apixaban 2.5 mg twice daily (b.i.d) or warfarin. Purpose To determine whether the apixaban dose adjustment in ARISTOTLE resulted in similar efficacy and safety compared to warfarin. Methods The effects of apixaban 2.5 mg b.i.d versus warfarin on stroke or systemic embolism, major bleeding and death in ARISTOTLE patients with ≥2 dose-reduction criteria were compared with the effects of apixaban 5 mg b.i.d in patients with 0 or 1 dose-reduction criterion. Results Of 751 (4.1%) patients with ≥2 dose-reduction criteria, 386 were assigned to apixaban 2.5 mg b.i.d and 365 to warfarin. Compared to patients with 0 or 1 dose reduction criteria (n=17,322), these patients had a higher risks of stroke/systemic embolism (HR =1.78; 95% CI [1.24–2.57]), major bleeding (HR =1.73; 95% CI [1.28–2.32]) and death (HR=3.21; 95% CI [2.69–3.83]), irrespective of whether they were assigned to apixaban or warfarin. The benefits of apixaban 2.5 mg b.i.d compared with warfarin on stroke or systemic embolism, major bleeding, and death in patients with ≥2 dose-reduction criteria were consistent with that of apixaban 5 mg b.i.d in patients with either 0 or 1 dose-reduction criteria (Figure). Conclusions While they are at higher overall risk, patients with appropriate dose reduction criteria have consistent benefits with apixaban 2.5 mg b.i.d. over warfarin. Additional analyses investigating the relationship between apixaban dose and both apixaban plasma concentrations and levels of thrombosis biomarkers are underway. Acknowledgement/Funding Bristol-Myers Squibb and Pfizer, Inc.

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