Dataset Information

Real-World Rivaroxaban and Apixaban Levels in Asian Patients With Atrial Fibrillation.

ABSTRACT: This study aims to measure the plasma levels of rivaroxaban and apixaban among Asian patients with atrial fibrillation and compare the results with expected drug levels from clinical studies. A total of 73 patients taking rivaroxaban and 105 patients taking apixaban were enrolled. Peak and trough levels were measured using ultra-high performance liquid chromatography with tandem mass spectrometry. The percentage of those with drug levels within the expected range reported in clinical studies was significantly higher in the apixaban group than in the rivaroxaban group, both for trough (84.8% vs. 64.4%; P = 0.002) and peak levels (76.9% vs. 33.8%; P < 0.001). After adjusting for age, sex, kidney function, appropriate dose, and adherence, patients taking rivaroxaban were still less likely to have peak and trough levels within the expected drug levels. Our real-world data suggests that Asian patients taking rivaroxaban are more likely to have out-of-expected drug levels than those taking apixaban.

SUBMITTER: Lin SY

PROVIDER: S-EPMC6977317 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Real-World Rivaroxaban and Apixaban Levels in Asian Patients With Atrial Fibrillation.

Lin Shin-Yi SY Kuo Ching-Hua CH Yeh Shin-Joe SJ Tsai Li-Kai LK Liu Yen-Bin YB Huang Chih-Fen CF Tang Sung-Chun SC Jeng Jiann-Shing JS

Clinical pharmacology and therapeutics 20190914 1

This study aims to measure the plasma levels of rivaroxaban and apixaban among Asian patients with atrial fibrillation and compare the results with expected drug levels from clinical studies. A total of 73 patients taking rivaroxaban and 105 patients taking apixaban were enrolled. Peak and trough levels were measured using ultra-high performance liquid chromatography with tandem mass spectrometry. The percentage of those with drug levels within the expected range reported in clinical studies was ...[more]

PMID: 31376150

Similar Datasets

Project description:Direct oral anticoagulants (DOACs), such as rivaroxaban, reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). However, it is still unclear whether the stroke reduction benefit outweighs the bleeding risk in elderly Japanese patients with NVAF. The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a real-world, prospective observational, post-marketing surveillance study on the safety and effectiveness of rivaroxaban in Japanese clinical practice. This sub-analysis evaluated the clinical outcomes of elderly patients aged???75 years. At the 1-year follow-up, there were 4,685 (48.91%) and 4,893 (51.09%) patients aged???75 and?<?75 years, respectively. Safety and effectiveness outcomes were compared between patients aged???75 years and those aged?<?75 years, and among 3 elderly sub-populations (age ranges: 75-79, 80-84, and???85 years). Patients aged???75 years had higher rates of major bleeding [2.22 vs. 1.35 events per 100 patient-years, hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.17-2.28] and composite of stroke (ischemic or hemorrhagic)/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI) (2.41 vs. 1.21 events per 100 patient-years, HR 1.97, 95% CI 1.40-2.77) compared to patients aged?<?75 years. Intracranial hemorrhage rates were?<?1 event per 100 patient-years in both groups (0.85 vs. 0.59 events per 100 patient-years, HR 1.43, 95% CI 0.85-2.40). Kaplan-Meier curves of major bleeding and stroke/non-CNS SE/MI showed that no significant differences of cumulative event rates were identified among the 3 elderly sub-populations. Stepwise Cox regression analyses revealed that creatinine clearance (CrCl) (<50 mL/min), hepatic impairment, and hypertension were specific predictors for major bleeding and no specific predictors were found for stroke/non-CNS SE/MI in patients aged???75 years. In conclusion, safety and effectiveness event rates were higher in patients aged???75 years compared with those aged?<?75 years, yet, no distinct differences were observed among the 3 elderly sub-populations.

Project description:Background and purposeComparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.

Project description:BackgroundLimited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs).ObjectivesTo compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States.Methods and resultsA retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan(®) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co-medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin.ConclusionAmong newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings.

Project description:Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70-0.84, I 2 : 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62-0.84, I 2 : 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58-0.73, I 2 : 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

Project description:Purpose:We conducted this study to assess the real-world prevalence, nature, predictors, and clinical necessity of apixaban pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions in patients with non-valvular atrial fibrillation (NVAF) at a tertiary medical institution in Saudi Arabia. Patients and Methods:An observational retrospective cohort analysis was conducted in adult patients diagnosed with NVAF receiving apixaban for stroke prevention from the period of June 2015 to May 2019. Results:Of the 1271 patients included in the analysis, 611 (48.1%) patients had potential PD- or PK-drug interactions with apixaban. Of those, 490 (38.6%) patients had potential PD drug-drug interactions (DDIs) and 121 (9.5%) patients had potential PK-DDIs. PD-DDIs with apixaban were mainly with antiplatelet therapy followed by non-steroidal anti-inflammatory drugs and antidepressants. PK-DDIs with apixaban were mainly with combined P-gp/CYP3A4 inhibitors or inducers. History of minor bleeding was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.455 (OR 1.58; 95% CI 1.01-2.45); p<0.05. History of acute coronary syndrome was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.515 (OR 1.60; 95% CI 1.36-1.99); p<0.05. History of heart failure was positively correlated with PK-DDIs with apixaban, ß coefficient = 0.459 (OR 1.58; 95% CI 1.07-2.35); p<0.05. Almost 15% of the included patients had no clinical indication to receive the potential interacting drug with apixaban and about 20% of them were assuming an inappropriate apixaban dose according to the product package insert. Conclusion:Pharmacodynamics and pharmacokinetics interactions are common in more than half of the patients with NVAF receiving apixaban for stroke prevention in this real-world analysis. Some of these interacting medications are not indicated. Drug-drug interactions should always be considered and monitored with apixaban with a regular assessment of the need for any interacting medication.

Dataset Information

Real-World Rivaroxaban and Apixaban Levels in Asian Patients With Atrial Fibrillation.

Publications

Real-World Rivaroxaban and Apixaban Levels in Asian Patients With Atrial Fibrillation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets