Different Coagulation Indicators in Predicting Clinical Outcomes for Patients With Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

Liu, Zhiyan; Zhang, Hanxu; Xie, Qiufen; Mu, Guangyan; Zhou, Shuang; Wang, Zining; Wang, Zhe; Jiang, Jie; Xiang, Qian; Chen, Yimin

doi:10.1016/j.clinthera.2020.08.001

Cited by 5 publications

(6 citation statements)

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“…Traditional coagulation indicators, including PT and APTT, were generally prolonged in a concentration-dependent pattern for dabigatran patients. [30][31][32][33] Anti-FIIa activity, as a specific test determined by chromogenic assay, has been recommended, and it demonstrated that peak anti-FIIa activity could be an indicator for predicting bleeding outcomes of dabigatran. 32,33 Consequently, our study focused on genetic variation on the direct outcomes of bleeding and indirect outcomes of PD, including anti-FIIa activity, APTT and PT.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, PD indices determined qualitatively and quantitatively might be more conveniently accessible. Traditional coagulation indicators, including PT and APTT, were generally prolonged in a concentration‐dependent pattern for dabigatran patients 30–33 . Anti‐FIIa activity, as a specific test determined by chromogenic assay, has been recommended, and it demonstrated that peak anti‐FIIa activity could be an indicator for predicting bleeding outcomes of dabigatran 32,33 .…”

Section: Discussionmentioning

confidence: 99%

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Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study

Xiang

Xie

Liu

et al. 2022

Clinical & Translational Med

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Introduction To identify the potential factors responsible for the individual variability of dabigatran, we investigated the genetic variations associated with clinical outcomes and pharmacodynamics (PD) in Chinese patients with nonvalvular atrial fibrillation (NVAF). Materials and methods Chinese patients with NVAF taking dabigatran etexilate with therapeutic doses were enrolled. The primary (bleeding events) and secondary (thromboembolic and major adverse cardiac events) outcomes for a 2‐year follow‐up were evaluated. Peak and trough PD parameters (anti‐FIIa activity, activated partial thromboplastin time and prothrombin time) were detected. Whole‐exome sequencing, genome‐wide sequencing and candidate gene association analyses were performed. Results There were 170 patients with NVAF treated with dabigatran (110 mg twice daily) who were finally included. Two single‐nucleotide polymorphisms (SNPs) were significantly related with bleeding, which include UBASH3B rs2276408 (odds ratio [OR] = 8.79, 95% confidence interval [CI]: 2.99–25.83, p = 7.77 × 10−5 at sixth month visit) and FBN2 rs3805625 (OR = 8.29, 95% CI: 2.87–23.89, p = 9.08 × 10−5 at 12th month visit), as well as with increased trends at other visits (p < .05). Furthermore, minor allele carriers of 16 new SNPs increased PD levels, and those of one new SNP decreased PD values (p < 1.0 × 10−5). Lastly, 33 new SNPs were found to be associated with bleeding and PD among 14 candidate genes. Unfortunately, the low number of secondary outcomes precluded further association analyses. Conclusions Genetic variations indeed affected bleeding and PD in Chinese patients with NVAF treated with dabigatran. The functions of these suggestive genes and SNPs might further be explored and verified in more in vivo and in vitro investigations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study

Xiang

Xie

Liu

et al. 2022

Clinical & Translational Med

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“…We are also still learning about the role of coagulation test monitoring as there are limited data evaluating anti-FXa assays and the association with clinical outcomes. [29][30][31][32] The lack of routine monitoring is another benefit to using DOACs and perhaps there are certain criteria that warrant closer monitoring, but the therapeutic index of DOACs has yet to be fully elucidated. When these aspects are clear, we will be able to individualize and optimize apixaban therapy.…”

Section: Discussionmentioning

confidence: 99%

Critical Analysis of Apixaban Dose Adjustment Criteria

Ryu

et al. 2021

Clin Appl Thromb Hemost

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Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous thromboembolism (VTE). Dose adjustment is based on age, weight, and serum creatinine in NVAF, while there are no recommended adjustment criteria for VTE. Such adjustment is unconventional compared to other commonly used medications. The objective of this manuscript is to critically analyze each apixaban dosing adjustment criterion and its associated outcomes. PubMed articles from March 2013 to March 2020 were selected with search terms “apixaban,” and “dose adjustment,” “adjustment,” or “adjustment criteria.” Pharmacokinetic studies demonstrated increased apixaban exposure in patients >65 years of age, those with extreme body weights, and those with advanced renal impairment, though post-hemodialysis dosing may off-set the elevated apixaban exposure. However, clinical data show that among patients >75 years, <60 kg, and with estimated glomerular filtration rate <50 mL/min, including those on dialysis, there is no reduction in apixaban safety or efficacy. Published literature describes variable dosing strategies utilized in clinical practice. Overall, apixaban dose adjustment criteria may need to be re-evaluated.

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“…In contrast to the routine coagulation tests, such as PT-INR or activated partial thromboplastin time (aPTT), the monitoring of anti-FXa activity is not widely available in clinical practice. Previous studies indicated that FXa inhibitors were associated with a concentration-dependent prolongation of the PT [ 6 , 7 , 8 ]. PT-INR is rapidly available and may help the clinicians evaluate the possibility of recent exposures of FXa-inhibitors in several emergent conditions, such as urgent procedures, major bleeding, or an acute stroke [ 2 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…For dabigatran, the aPTT may provide a quantitative assessment of dabigatran serum level and anticoagulant activity. The relationship between dabigatran serum concentration and the aPTT value followed a curvilinear curve with a quadratic curve [ 2 , 7 , 8 ]. However, previous studies investigating whether the measurements of PT-INR or aPTT could be useful for monitoring or correlating with the concentration of rivaroxaban and dabigatran have showed conflicting results [ 7 , 8 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Prothrombin Time-International Normalized Ratio Predicts the Outcome of Atrial Fibrillation Patients Taking Rivaroxaban

et al. 2022

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Background: Although direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) are considered to be safe, over or under anticoagulation and increased bleeding or thromboembolic risk are still considered individually. We aimed to investigate whether there is an association between prothrombin time and international normalized ratio (PT-INR) or activated partial thromboplastin time (aPTT) ratio, and the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran. Methods: This multi-center cohort study in Taiwan included 3192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention where data about PT-INR and aPTT were available. Results: For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level < 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR < 1.1 (aHR:0.57; [95%CI: 0.37–0.87]; p = 0.01). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1–1.2 and 1.3–1.4 than those with an aPTT ratio < 1.1. Conclusions: In AF patients, rivaroxaban with an INR ≥ 1.5 was associated with a lower risk of IS/SE. PT-INR or aPTT ratios were not associated with bleeding events for rivaroxaban or dabigatran. INR may help predict the outcome of AF patients who take rivaroxaban.

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Different Coagulation Indicators in Predicting Clinical Outcomes for Patients With Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

Cited by 5 publications

References 58 publications

Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study

Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study

Critical Analysis of Apixaban Dose Adjustment Criteria

Prothrombin Time-International Normalized Ratio Predicts the Outcome of Atrial Fibrillation Patients Taking Rivaroxaban

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