Ischemic stroke, hemorrhage, and mortality in patients with non-valvular atrial fibrillation and renal dysfunction treated with rivaroxaban: sub-analysis of the EXPAND study.
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SUBMITTER: Atarashi H
PROVIDER: S-EPMC8332581 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:For Japanese patients with non-valvular atrial fibrillation (NVAF), the risk of stroke and major bleeding events was assessed by using the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The risk factors for embolism and major bleeding under DOAC may be different from current reports. We analyzed the data set of the EXPAND Study to determine the risk factors for events among Japanese NVAF patients in the era of direct oral anticoagulant. Using the data of EXPAND Study, the validity for predictability of the CHADS2, CHA2DS2-VASc, and HAS-BLED scores was identified using the receiver operating characteristic curve analysis. Multivariate analysis was performed with the Cox proportional hazard model to determine the independent risk factors for stroke/systemic embolism and major bleeding among NVAF patients receiving rivaroxaban. Explanatory variables were selected based on the univariate analysis. A total of 7141 patients (mean age 71.6 ± 9.4 years, women 32.3%, and rivaroxaban 15 mg per day 56.5%) were included. Incidence rates of stroke/systemic embolism and major bleeding were 1.0%/year and 1.2%/year, respectively. The multivariate analysis revealed that only history of stroke was associated with stroke/systemic embolism (hazard ratio 3.4, 95% confidence interval 2.5-4.7, p < 0.0001). By contrast, age (1.7, 1.1-2.6, p = 0.0263), creatinine clearance (CrCl) 30-49 mL/min (1.6, 1.2-2.2, p = 0.0011), liver dysfunction (1.7, 1.1-2.8, p = 0.0320), history/disposition of bleeding (1.8, 1.0-3.0, p = 0.0348), and concomitant use of antiplatelet agents (1.6, 1.2-2.3, p = 0.0030) were associated with major bleeding. This sub-analysis showed that some components of the HAS-BLED score were independently associated with major bleeding in Japanese NVAF patients receiving anticoagulation therapy by rivaroxaban. Additionally, CrCl value of 30-49 mL/min was an independent predictor of major bleeding in patients receiving rivaroxaban.
| S-EPMC6794239 | biostudies-literature
Project description:The EXPAND Study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). In this sub-analysis, we compared the differences in efficacy and safety between patients with and those without history of stroke or transient ischemic attack (TIA). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients aged ≥ 20 years [mean age 71.6 ± 9.4 (SD) years] who were being or planned to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for a mean period of 897.1 ± 206.8 days with a high follow-up rate (99.7%). The primary prevention group comprised patients without history of ischemic stroke or TIA (n = 5546, 77.7%), and the secondary prevention group comprised those with history of ischemic stroke or TIA (n = 1595, 22.3%). In the primary and secondary prevention groups, the incidence rate of stroke or SE (primary efficacy endpoint) was 0.7 and 2.2%/year, respectively (P < 0.001), and the incidence rate of major bleeding (primary safety endpoint) was 1.2 and 1.5%/year, respectively (P = 0.132). For major bleeding events, the incidence rate of intracranial bleeding was 0.4 and 0.8%/year (P = 0.002) in the primary and secondary prevention groups, respectively. This sub-analysis of the EXPAND Study showed that the Japan-specific dosages of rivaroxaban were effective and safe in Japanese NVAF patients with and those without ischemic stroke or TIA in routine clinical practice.
| S-EPMC6347661 | biostudies-literature
Project description:We have a great interest in the article in Journal of Atherosclerosis and Thrombosis by Suzuki et al. titled Complex Aortic Arch Atherosclerosis in Acute Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation. The authors demonstrated that 38.7% transesophageal echocardiography-derived complex aortic arch plaques (CAPs) among 106 patients with acute ischemic strokes with atrial fibrillation (AF), suggesting that patients with acute ischemic stroke and AF often had CAPs. The atheromatous lesions at the aortic arch are one of the causes of ischemic strokes. The cause of acute ischemic strokes in patients with AF could not only be cardiogenic embolisms due to AF but also aortogenic embolisms due to CAPs. The possibility of concomitant CAPs should be considered for stroke patients with AF. Non-obstructive general angioscopy has the possibility to detect aortic plaques in the aortic arch more accurately than TEE and might help to diagnose atheromatous plaques and embolic materials in the aortic arch. Further studies are needed to elucidate the causes of ischemic strokes and are expected to improve the outcomes for acute ischemic strokes in patients with AF.
| S-EPMC8265922 | biostudies-literature
Project description:BackgroundWe aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation.Materials and methodsUsing discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke.ResultsAmong 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5-8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5-4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0-2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6-2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5-1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9.ConclusionsIn a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores.
| S-EPMC4689346 | biostudies-literature
Project description:Background and purposeAnticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH).MethodsWe conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA2DS2-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer.ResultsWe identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years.ConclusionsPatients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.
| S-EPMC7751804 | biostudies-literature
Project description:There is a clinically staggering burden of disease stemming from cerebrovascular events, of which a majority are ischemic in nature and many are precipitated by atrial fibrillation (AF). AF can occur in isolation or in association with myocardial or structural heart disease. In the latter case, and when considering health at an international level, congenital and acquired valve-related diseases are frequent contributors to the current pandemic of AF and its clinical impact. Guidelines crafted by the American Heart Association, American College of Cardiology, European Society of Cardiology and Heart Rhythm Society underscore the use of vitamin K antagonists (VKAs) among patients with valvular heart disease, particularly in the presence of concomitant AF, to reduce the risk of ischemic stroke of cardioembolic origin; however, the non-VKAs, also referred to as direct, target-specific or new oral anticoagulants (NOACs), have not been actively studied in this particular population. In fact, each of the new agents is approved in patients with AF not caused by a valve problem. The aim of our review is to carefully examine the available evidence from pivotal phase 3 clinical trials of NOACs and determine how they might perform in patients with AF and concomitant valvular heart disease.
| S-EPMC4897010 | biostudies-other
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure.
| S-EPMC3968084 | biostudies-other
Project description:Background and Purpose- Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA2DS2-VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods- We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)-a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA2DS2-VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results- Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions- Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00930280.
| S-EPMC7112469 | biostudies-literature
Project description:ObjectiveTo compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD).MethodsUsing Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis.ResultsAmong 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31).ConclusionsWe found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD.Trial registration numberNCT00403767; Post-results.
| S-EPMC4941167 | biostudies-literature
Project description:The management of acute ischemic stroke during anticoagulation with a novel oral anticoagulant (NOAC) is challenging because intravenous thrombolysis is contraindicated because of a putative increased risk of intracerebral hemorrhagic complications. We examined the risk of secondary postischemic hemorrhage after thrombolysis in rodents pretreated with rivaroxaban or warfarin. Mice were pretreated with either rivaroxaban (30 mg/kg), warfarin (target international normalized ratio 2 to 3) or vehicle. After 2 or 3 hours, middle cerebral artery occlusion (MCAO), mice received 9 mg/kg recombinant tissue plasminogen activator. Twenty-four hours after MCAO, secondary hemorrhage was quantified using a macroscopic hemorrhage score and hemoglobin spectrophotometry. Blood-brain barrier (BBB) permeability was measured by Evans Blue spectrofluorometry. To increase the validity of our findings, experiments were also performed using a thromboembolic model in anticoagulated rats. Infarct size did not differ among groups. Pretreatment with warfarin led to significantly more secondary hemorrhage compared with rivaroxaban and nonanticoagulated controls after 2- and 3-hour ischemia in mice as well as in rats. Blood-brain barrier permeability was significantly higher in the warfarin group compared with rivaroxaban and control. Thus, rivaroxaban in contrast to warfarin does not increase secondary hemorrhage after thrombolysis in experimental cerebral ischemia. Less effects of rivaroxaban on postischemic BBB permeability may account for this difference.
| S-EPMC3948130 | biostudies-literature