Dataset Information

Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

ABSTRACT: Objective: This study's objective was to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy consisting of rivaroxaban, clopidogrel, and aspirin as part of dual or triple therapy. Methods: A prospective observational study was conducted in two PCI centers in Moscow, the Russian Federation, from 2017 to 2018. One hundred patients with ACS and AF were enrolled. Prospective follow-ups continued for 12 months. Results: A total of 36 patients experienced bleeding events, with 10 experiencing major bleeding based on the BARC scale and 17 experiencing major bleeding based on the ISTH scale. The following predictors associated with an increased number of major bleeding events were identified: for the ISTH scale, a Css min. of rivaroxaban of >137 pg/mL (5.94 OR, (95% CI, 3.13-12.99; p < 0.004)) and carriage of the T allelic variant polymorphism ABCB1 rs4148738 (8.97 OR (95% CI, 1.48-14.49; p < 0.017)), as well as for the BARC scale (5.76 OR (95% CI, 2.36-9.87; p < 0.018)). Conclusions: Measuring residual steady-state rivaroxaban concentrations and determining the carriage of the T allelic variant polymorphism ABCB1 rs4148738 may be applicable to high-risk patients for subsequent antithrombotic therapy modification.

SUBMITTER: Baturina O

PROVIDER: S-EPMC10532904 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

Baturina Olga O Chashkina Maria M Andreev Denis D Mirzaev Karin K Bykova Alexandra A Suvorov Alexandr A Yeryshova Daria D Suchkova Svetlana S Sychev Dmitry D Syrkin Abram A

Journal of personalized medicine 20230912 9

<b>Objective:</b> This study's objective was to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy consisting of rivaroxaban, clopidogrel, and aspirin as part of dual or triple therapy. <b>Methods:</b> A prospective observational study was conducted in two PCI centers in Moscow, the Russian Federation, from 2017 to 2018. One hundred patients with ACS and AF were enrolled. Prospec ...[more]

PMID: 37763139

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Project description:BackgroundThe efficacy of double antithrombotic therapy (DAT) vs. triple antithrombotic therapy (TAT) for prevention of bleeding and ischemic events in patients with atrial fibrillation following percutaneous coronary intervention (PCI) is unclear in those subgroups defined by the 5 factors (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor). We aimed to assess the efficacy of DAT vs TAT in these patient subgroups.MethodsWe searched PubMed and relevant websites to include related randomized controlled trials (RCTs). Two endpoints of interest were clinically significant bleeding and major adverse cardiac events (MACE). Meta-analysis was performed stratified by 5 factors of interest (i.e., sex, age, race, history of diabetes, and type of P2Y12 inhibitor) to obtain pooled hazard ratio (HR) and 95% confidence interval (CI). Meta-regression analysis was conducted to evaluate subgroup effects. We detected publication bias by Egger test and funnel plots.ResultsWe included 4 RCTs for meta-analysis. DAT vs TAT significantly reduced the risk of clinically significant bleeding (HR 0.56, 95% CI 0.50-0.63). This effect of DAT was observed in most subgroups of interest (HR ranged from 0.54 to 0.69), and was consistent across various subgroups defined by each of the 5 factors of interest (Psubgroup ranged from 0.290 to 0.794). DAT vs TAT led to the similar risk of MACE (HR 0.98, 95% CI 0.89-1.08). This effect of DAT was observed in all subgroups of interest (all 95% CIs of HRs were across 1.0), and was consistent across various subgroups defined by each of the 5 factors of interest (Psubgroup ranged from 0.308 to 0.828). Publication bias was found only in one subgroup.ConclusionsCompared with TAT, DAT significantly reduces the risk of clinically significant bleeding and leads to the similar risk of MACE in patients with atrial fibrillation following PCI, irrespective of sex, age, race, history of diabetes, and type of P2Y12 inhibitor used at baseline.

Project description:ObjectiveTo examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.DesignSystematic review and network meta-analysis.Data sourcesA systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.Eligibility criteria for selecting studiesRandomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.ResultsFor stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.ConclusionsCompared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.Systematic review registration numberPROSPERO registry-CRD42012002721.

Project description:BackgroundUse of oral anticoagulation therapy in patients with atrial fibrillation (AF) involves a trade-off between a reduced risk of ischemic stroke and an increased risk of bleeding events. Different anticoagulation therapies have different safety profiles and data on the societal costs of both ischemic stroke and bleeding events are necessary for assessing the cost-effectiveness and budgetary impact of different treatment options. To our knowledge, no previous studies have estimated the societal costs of bleeding events in patients with AF. The objective of this study was to estimate the 3-years societal costs of first-incident intracranial, gastrointestinal and other major bleeding events in Danish patients with AF.MethodsThe study was an incidence-based cost-of-illness study carried out from a societal perspective and based on data from national Danish registries covering the period 2002-2012. Costs were estimated using a propensity score matching and multivariable regression analysis (first difference OLS) in a cohort design.ResultsAverage 3-years societal costs attributable to intracranial, gastrointestinal and other major bleeding events were 27,627, 17,868, and 12,384 EUR per patient, respectively (2015 prices). Existing evidence shows that the corresponding costs of ischemic stroke were 24,084 EUR per patient (2012 prices). The average costs of bleeding events did not differ between patients with AF who were on oral anticoagulation therapy prior to the event and patients who were not.ConclusionsThe societal costs attributable to major bleeding events in patients with AF are significant. Intracranial haemorrhages are most costly to society with average costs of similar magnitude as the costs of ischemic stroke. The average costs of gastrointestinal and other major bleeding events are lower than the costs of intracranial haemorrhages, but still substantial. Knowledge about the relative size of the costs of bleeding events compared to ischemic stroke in patients with AF constitutes valuable evidence for decisions-makers in Denmark as well as in other countries.

Project description:Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995.

Dataset Information

Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

Publications

Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

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