Safety Of Oral Anticoagulants Research Articles

Oral anticoagulant monotherapy vs oral anticoagulant/antiplatelet therapy for the management of atrial fibrillation and stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Background- The efficacy and safety of oral Anticoagulation (OAC)with either Warfarin or Direct oral anticoagulants (DOACs) as compared with combination therapy of oral anticoagulant and antiplatelet (OAC + APT) in patients with atrial fibrillation and stable coronary artery disease more than 1 year after stenting is not known. Methods-Electronic databases ( PubMed, Embase, Scopus) were searched from inception to December 28th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05. The primary efficacy end point was MACCE definied as composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. Results- A total of seven studies with 81,303(OAC = 56,633; OAC + APT = 24670) participants were included. There was no statistically significant differences in MACCE among patients treated using OAC monotherapy compared with those treated with OAC + APT (HR 1.09; 95% CI 0.93-1.29; p = 0.28). OAC + APT was associated with a significantly higher risk of major bleeding compared with OAC monotherapy (HR 1.65; 95% CI 1.30-2.11; p < 0.0001) Conclusion- Amongst patients with atrial fibrillation and concomitant stable coronary artery disease, OAC monotherapy is non-inferior to combination therapy with OAC and single antiplatelet agent. OAC monotherapy reduced the risk for major or life-threatening bleeding events, while not increasing the risk for major adverse cardiovascular events. Abstract Figure.

Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism

BackgroundWhether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern. MethodsWe evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study. ResultsAnticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55–2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34–1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51–1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40–1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66–4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62–1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4. ConclusionIn our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.

Oral anticoagulants in extremely-high-risk, very elderly (>90 years) patients with atrial fibrillation

The prevalence and incidence of atrial fibrillation (AF) increase with age. However, older patients often are denied oral anticoagulation (OAC), especially if they are "very elderly" (age ≥90 years) and perceived to be high risk for bleeding, for example, those with a history of intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), or chronic kidney disease. The purpose of this study was to investigate the effectiveness and safety of OAC in this high-risk, very elderly group. We used the Taiwan National Health Insurance Research Database to identify high-risk, very elderly subjects taking OAC, either warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), and compared them to non-OAC users for the composite net clinical endpoint of ischemic stroke, ICH, major bleeding, or mortality. We studied 7362 subjects (mean age 92.5 years), of whom 1737 were taking NOACs, 670 warfarin, and 4955 non-OACs. Compared to non-OACs, warfarin was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163; 95% confidence interval [CI] 1.052-1.287), whereas NOACs were associated with a lower risk (aHR 0.763; 95% CI 0.702-0.830). After propensity matching, NOACs were associated with a lower risk of events compared to non-OACs or warfarin, whereas warfarin had a similar risk compared to non-OACs. Warfarin was associated with a similar or even higher risk of composite clinical outcomes compared to non-OACs. NOACs were associated with a lower risk of composite endpoint compared to warfarin or non-OACs, and their use still should be considered in these high-risk, very elderly AF patients.

Anticoagulation with or without antiplatelet therapy after transcatheter aortic valve replacement, when less is more: a meta-analysis

Abstract Background About 40% of patients undergoing transcatheter aortic valve replacement (TAVR) have a history of atrial fibrillation (AF) and an additional 10% develop AF after TAVR. However, there is paucity of data regarding the optimal antithrombotic regimen following TAVR in patients with a clinical indication for oral anticoagulants (OAC). Purpose To compare the prognostic impact of OAC plus at least one antiplatelet agent (APT) versus OAC therapy alone in patients undergoing TAVR. Methods We systematically searched the literature for studies evaluating the comparative efficacy and safety of OAC + APT versus OAC alone in TAVR. Random-effect meta-analysis was performed comparing clinical outcomes between the two groups. All-cause mortality and cardiovascular mortality were the efficacy outcomes. Stroke and major bleeding, defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety outcome. Results Overall, 398 titles and abstracts were identified through database searching. Four observational studies were selected, for a total of 1929 patients. After a median follow-up of 18.5 months (IQR 11.3–29.3), OAC + APT increased major bleeding events compared to OAC alone (OR=1.79; 95% CI 1.21–2.66; P=0.004) with no difference in stroke (OR 01.02; 95% CI 0.52–2.01; P=0.95), all-cause mortality (OR=1.07; 95% CI 0.78–1.47; P=0.66) and cardiovascular mortality (OR=1.08; 95% CI 0.79–1.47; P=0.62). Conclusion A combination strategy of OAC + APT provides increased risk of bleeding compared to OAC therapy alone in patients undergoing TAVR with similar outcomes in terms of stroke, all-cause mortality and cardiovascular mortality; therefore, when feasible, it should be advised not to add APT on top of OAC therapy in patients without other clinical indications for APT treatment. Funding Acknowledgement Type of funding source: None

Oral anticoagulants in extremely high risk very elderly (>90 years) patients with Atrial Fibrillation

Abstract Background The prevalence and incidence of atrial fibrillation (AF) increases with age, resulting in a high mortality and morbidity, especially from stroke and systemic thromboembolism (SSE). Nonetheless, the elderly are often denied oral anticoagulants (OACs), especially if they are “very elderly” (age ≥90 years) and perceived to be “high risk” of bleeding, for example, those with a history of intracranial haemorrhage (ICH), gastrointestinal bleeding or chronic kidney disease. We aimed to investigate the effectiveness and safety of OAC in this “high risk” very elderly group. Methods We used the Taiwan National Insurance Database to identify “high risk” very elderly subjects taking OACs, whether warfarin or non-vitamin K antagonist OACs (NOACs), who were compared to non-OAC users for the composite clinical endpoint of “ischemic stroke, ICH, major bleeding or mortality”. Propensity score matching was used for comparisons of the treatment groups. Results We studied 7,362 subjects (48.4% males; mean age 92.5 years, SD 2.78), of which 1737 were taking NOACs, 670 warfarin and 4955 were non-OAC users. Using non-OAC users as the reference group, warfarin use in “high risk” very elderly patients was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163, 95% CI 1.052–1.287), while NOACs were associated with a lower risk (aHR 0.763, 0.702–0.830). After propensity matching, NOACs were associated with a lower risk of events compared to “non-OAC use” or “warfarin”, while warfarin had a similar risk compared to non-OAC use (Figure). Conclusions Warfarin was associated with a similar (after propensity matching) or higher (Cox model before matching) risk of the composite clinical outcome compared to non-OAC use. NOACs were associated with a significantly lower risk of the composite clinical outcome compared to warfarin or non-OAC use. NOACs should be considered as the preferred OAC strategy in these “high risk” very elderly AF patients. Funding Acknowledgement Type of funding source: None

Comparing anticoagulation therapy alone versus anticoagulation plus single antiplatelet drug therapy after transcatheter aortic valve implantation in patients with an indication for anticoagulation: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of oral anticoagulation (OAC) therapy alone versus OAC plus single antiplatelet therapy (SAPT) in patients with an indication for chronic OAC (mostly due to atrial fibrillation) after transcatheter aortic valve implantation (TAVI). A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases to identify relevant studies. Data was extracted from the eligible studies and outcomes expressed as relative risks (RRs) with 95% confidence intervals (CIs). Five studies comprising 1344 patients with an indication for chronic OAC and undergoing TAVI were included. Of the 1344 patients, 480 patients received OAC therapy alone and 864 patients received OAC plus SAPT. There were no significant differences between OAC alone versus OAC plus SAPT in all-cause mortality (RR = 1.05, 95% CI 0.84-1.30, p = 0.69) and ischemic stroke (RR = 0.95, 95% CI 0.95-1.61, p = 0.86). However, OAC alone was associated with significantly lower risks of all bleeding events (RR = 0.62, 95% CI 0.49-0.69, p < 0.0001) and major and/ life-threatening bleeding events (RR = 0.57, 95% CI 0.42-0.76, p = 0.0002) compared to OAC plus SAPT. In patients with an indication for chronic anticoagulation, post-TAVI antithrombotic therapy with OAC alone compared to OAC plus SAPT may be not significantly different in reducing all-cause mortality and ischemic stroke, but has an important benefit in a significantly lower risk of all bleeding and major and/life-threatening bleeding events.

Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy.

Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6-9). Compared to warfarin, apixaban [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.52-0.68], and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban. In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favourable for NOACs vs. warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.

Efficacy and Safety of Oral Anticoagulants in Patients with Systolic Heart Failure in Sinus Rhythm: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Cohort Studies.

Introduction There is conflicting evidence on the risk–benefit ratio of oral anticoagulants (OAC) in heart failure (HF) patients without atrial fibrillation. We aimed to evaluate the efficacy and safety of OAC in HF patients in sinus rhythm. Methods A systematic literature search was conducted using PubMed and Embase. We included randomized controlled trials (RCT) and cohort studies, comparing OAC with antiplatelet or no treatment/placebo in patients with HF. Outcomes evaluated were stroke, myocardial infarction (MI), all-cause mortality, and major bleeding. Results Five RCTs and three cohort studies were included. OAC was associated with a reduced risk of ischemic stroke when compared with no treatment/placebo (odds ratio [OR] = 0.67, 95% confidence interval [CI]: [0.47, 0.94]) and antiplatelet therapy (OR = 0.55, 95% CI: [0.37, 0.81]). No significant reduction was found in MI, when OAC was compared with no treatment/placebo (OR = 0.82, 95% CI: [0.63, 1.07]) or antiplatelet therapy (OR = 1.04, 95% CI: [0.60, 1.81]). The all-cause mortality analysis showed no significant reduction when comparing OAC with no treatment/placebo (OR = 0.99, 95% CI: [0.87, 1.12]) or antiplatelet therapy (OR = 1.00, 95% CI: [0.86, 1.16]). The nonsignificant effect of OAC on all-cause mortality was supported by a meta-analysis of the three cohort studies (OR = 1.02, 95% CI: [0.75, 1.38]). Patients treated with OAC had a significantly higher risk of major bleeding than patients receiving antiplatelet therapy (OR = 2.16, 95% CI: [1.55, 3.00]) and a numerically higher risk when compared with no treatment/placebo (OR = 2.38, 95% CI: [0.87, 6.49]). Conclusion The present study does not support the routine use of OAC in patients with HF in sinus rhythm.

Incidence and outcomes of patients with atrial fibrillation and major bleeding complications: from the TREAT-AF study

Optimal stroke prevention strategies for patients with atrial fibrillation (AF) who experience a major bleed are poorly defined. We sought to estimate the effectiveness and safety of oral anticoagulation (OAC) represcription after an OAC contraindication. TREAT-AF is a retrospective cohort study of patients with newly diagnosed AF (2004-2012), treated in the Veterans Health Administration. From this cohort, we identified patients with a contraindication to OAC after AF diagnoses, defined as incident intracranial bleeding, non-intracranial bleeding requiring hospitalization, or unrepaired cerebral aneurysm or aortic dissection. We used multivariate Cox proportional hazards to estimate the association of OAC prescription in the 90days following OAC contraindication to ischemic stroke and rebleeding. Among 167,190 patients with newly diagnosed AF (70 ± 11years, 1.7% female, CHA2DS2-VASc 2.7 ± 1.7), 19,285 patients (11.5%) had an incident bleed (n = 18,342) or an unrepaired cerebral aneurysm or aortic dissection (n = 943). For OAC-contraindicated patients with a CHA2DS2-VASc ≥2 (N = 16,194), OAC was represcribed in 4075 patients (25%) and was associated with a higher risk of non-intracranial bleeding (HR 1.49; 95% CI 1.37-1.61; p < 0.0001) but no difference in intracranial bleeding. There was a trend toward decreased stroke risk (HR 0.85; 95% CI 0.71-1.02; p0.09). Development of contraindication to OAC after diagnosis of AF is common (11.5%), with most events requiring hospitalization. OAC reinitiation was associated with non-intracranial bleeding risk, with a trend toward reduced stroke risk. These data suggest that stroke prevention approaches after major bleeding events could be beneficial if bleeding risk can be successfully mitigated.

Safety and Efficacy of Oral Anticoagulants for Atrial Fibrillation in Patients After Bariatric Surgery

Anticoagulation management is challenging in bariatric surgery patients, due to altered gastrointestinal anatomy and potentially reduced absorption. Few studies have evaluated clinical outcomes in this population. The objective of this study was to compare the efficacy and safety of oral anticoagulants in patients with and without a history of bariatric surgery. A retrospective, matched cohort study was conducted, utilizing data from the OptumLabs Data Warehouse. Patients ≥18 years old, with nonvalvular atrial fibrillation (NVAF), and treated with an oral anticoagulant between January 1, 2010 and December 31, 2018 were included. Outcomes were compared between bariatric and nonbariatric surgery patients. Secondary analysis compared warfarin to the direct oral anticoagulants (DOAC) in the bariatric cohort. The primary efficacy outcome was the rate of ischemic stroke and systemic embolism and the primary safety outcome was major bleeding. A total of 1,673 bariatric surgery and 155,619 nonbariatric surgery patients were identified. There was no significant difference in the rate of ischemic stroke or systemic embolism (0.83 vs 1.32 per 100 person years; Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.31 to 1.22; p = 0.17) or major bleeding (5.30 vs 4.87 per 100 person years; HR 1.05, 95% CI 0.80 to 1.37; p = 0.73) between bariatric and nonbariatric surgery patients. In bariatric surgery patients alone, efficacy and safety were similar with warfarin compared with the DOACs. Results of this study suggest that bariatric surgery patients are not at an increased thrombotic or bleeding risk when using oral anticoagulants for NVAF. DOACs may be a reasonable alternative to warfarin.

Antithrombotic treatment in patients with stroke and supracardiac atherosclerosis.

To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis. We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models. Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I2 = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I2 = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I2 = 46%). This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients.

Effectiveness and Safety of Oral Anticoagulants among NVAF Patients with Obesity: Insights from the ARISTOPHANES Study.

This ARISTOPHANES analysis examined stroke/systemic embolism (SE) and major bleeding (MB) among a subgroup of nonvalvular atrial fibrillation (NVAF) patients with obesity prescribed warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) in order to inform clinical decision making. A retrospective observational study was conducted among NVAF patients who were obese and initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013–30 September 2015, with data pooled from CMS Medicare and four US commercial claims databases. Propensity score matching was completed between NOACs and against warfarin in each database, and the results were pooled. Cox models were used to evaluate the risks of stroke/SE and MB. A total of 88,461 patients with obesity were included in the study. Apixaban and rivaroxaban were associated with a lower risk of stroke/SE vs. warfarin (HR: 0.63, 95% CI: 0.49–0.82 and HR: 0.84, 95% CI: 0.72–0.98). Dabigatran was associated with a similar risk of stroke/SE compared to warfarin. Compared with warfarin, apixaban and dabigatran had a lower risk of MB (HR: 0.54, 95% CI: 0.49–0.61 and HR: 0.75, 95% CI: 0.63–0.91). Rivaroxaban was associated with a similar risk of MB compared to warfarin. In this high-risk population with obesity, NOACs had a varying risk of stroke/SE and MB vs. warfarin.

Reader response: MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation.

We read, with interest, the impressive study by Marti-Fabregas et al.1 As discussed, the HERO study and the CROMIS-2 study together have elaborated on the safety of oral anticoagulation (OA) in patients with cerebral microbleeds (CMBs).1,2

Effectiveness and Safety of Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Diabetes Mellitus

ObjectiveTo address gaps in the data comparing non–vitamin K antagonist oral anticoagulants (NOACs) and warfarin among patients with nonvalvular atrial fibrillation (NVAF) and diabetes. Patients and MethodsA retrospective study was conducted on patients with NVAF and diabetes newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with Medicare data from the US Centers for Medicare & Medicaid Services and 4 other US commercial claims databases. One-to-one propensity score matching was completed between NOACs and warfarin and between NOACs in each database, and the results were pooled. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB). ResultsA total of 154,324 patients were included in the 6 matched cohorts, with a mean follow-up time of 6 to 8 months. Compared with warfarin, apixaban (hazard ratio [HR], 0.67; 95% CI, 0.57-0.77) and rivaroxaban (HR, 0.79; 95% CI, 0.71-0.89) were associated with a lower risk of stroke/SE; dabigatran (HR, 0.84; 95% CI, 0.67-1.07) was associated with a similar risk of stroke/SE. Apixaban (HR, 0.60; 95% CI, 0.56-0.65) and dabigatran (HR, 0.78; 95% CI, 0.69-0.88) were associated with a lower risk of MB; rivaroxaban (HR, 1.02; 95% CI, 0.94-1.10) was associated with a similar risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of MB. Compared with rivaroxaban, dabigatran was associated with a lower risk of MB. ConclusionThis study—the largest observational study to date of patients with NVAF and diabetes taking anticoagulants—found that NOACs were associated with variable rates of stroke/SE and MB compared with warfarin. Trial Registrationclinicaltrials.gov Identifier: NCT03087487

Correction to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study.

HomeStrokeVol. 51, No. 4Correction to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study Originally published23 Mar 2020https://doi.org/10.1161/STR.0000000000000227Stroke. 2020;51:e71This article corrects the followingEffectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation PatientsIn the article by Lip et al, “Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study,” which was published online on November 8, 2018, and appeared in the December 2018 issue of the journal (Stroke. 2018;49:2933–2944. doi: 10.1161/STROKEAHA.118.020232), corrections are needed.There was a minor transcription error that affected two hazard ratios in Figure 3D of the article. The hazard ratios needing correction are in the apixaban vs dabigatran major bleeding comparison in the renal disease subgroup analysis (Figure 3, Panel D, two “renal disease” rows). The hazard ratios without renal disease should be changed from 0.69 (0.56-0.84) to 0.80 (0.70-0.92) and with renal disease from 0.81 (0.58-1.14) to 0.74 (0.61-0.89). There was no change in the non-significance of the interaction and this error did not affect any text in the article.These corrections have been made to the online version of the article, which is available at https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.020232. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lorenzoni V, Pirri S and Turchetti G (2021) Cost-Effectiveness of Direct Non-Vitamin K Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Patients with Non-Valvular Atrial Fibrillation Based on Available “Real-World” Evidence: The Italian National Health System Perspective, Clinical Drug Investigation, 10.1007/s40261-021-01002-z, 41:3, (255-267), Online publication date: 1-Mar-2021. Related articlesEffectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation PatientsGregory Y.H. Lip, et al. Stroke. 2018;49:2933-2944 April 2020Vol 51, Issue 4 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/STR.0000000000000227PMID: 32202989 Originally publishedMarch 23, 2020 PDF download Advertisement

Correction to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study.

HomeStrokeVol. 51, No. 2Correction to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection to: Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study Originally published10 Jan 2020https://doi.org/10.1161/STR.0000000000000218Stroke. 2020;51:e44This article corrects the followingEffectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation PatientsOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 10, 2020: Ahead of Print In the article by Lip et al, “Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients: The ARISTOPHANES Study,” which was published online on November 8, 2018, and appeared in the December 2018 issue of the journal (Stroke. 2018;49:2933–2944. doi: 10.1161/STROKEAHA.118.020232), corrections are needed.ARISTOPHANES is a pooled analysis of data from 5 US claims databases. Due to an inadvertent error with the underlying data cut received by the authors for one of the databases (the CMS Medicare database), a proportion of Medicare patients who should have been included in the analysis were excluded from the study. Specifically, those excluded patients were newly diagnosed with atrial fibrillation and initiated anticoagulation therapy in the same calendar year (2014 or 2015).Authors have corrected the analyses by adding back those excluded patients. Results sections in the abstract and main body of the article, Table 1, Figures 1–3, Supplemental Tables II–XIII, and Supplemental Figure I have been changed to reflect the corrected analyses. These corrections have increased the sample size from 321 182 to 466 991 patients. The corrections did not result in material changes to the study findings or conclusions.These corrections have been made to the online version of the article, which is available at https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.020232. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesEffectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation PatientsGregory Y.H. Lip, et al. Stroke. 2018;49:2933-2944 February 2020Vol 51, Issue 2 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/STR.0000000000000218PMID: 31918618 Originally publishedJanuary 10, 2020 PDF download Advertisement

Oral Anticoagulation for Patients With Atrial Fibrillation on Long-Term Dialysis

BackgroundPatients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown. ObjectivesThis study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis. MethodsMEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding. ResultsThis study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant. ConclusionsThis meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.

ФИБРИЛЛЯЦИЯ ПРЕДСЕРДИЙ И ПРИВЕРЖЕННОСТЬ К ПЕРОРАЛЬНОЙ АНТИКОАГУЛЯНТНОЙ ТЕРАПИИ: РАЗБОР КЛИНИЧЕСКИХ СЛУЧАЕВ

Prevalence of atrial fibrillation (AF) is continuously increasing. Stroke in AF patients is the most unfavorable complication of arrhythmia, clinical course being severer, neurological deficit pronounced, and mortality higher compared to stroke patients without AF. Oral anticoagulation (OAC) results in significant reduction of stroke and systemic embolism but at the same time is compromised by haemorrhagic complications. High adherence to treatment is essential for effectiveness and safety of OAC. Nonetheless, poor adherence to treatment in case of chronic diseases requiring drug regimen remains unresolved. Social, economic and demographic factors, patient’s psychological markers, inertia of the healthcare system, formalism in the implementation of recommendations in routine clinical practice, violation of the continuity between inpatient and outpatient care, limited resources and other factors lead to low adherence among patients with AF. Refusal of OAC, intermittent treatment, delayed medication with OAC, failure to follow recommendations for the control of modifiable risk factors associated with anticoagulant therapy, are transformed into a high level of cardiovascular and cerebrovascular events in patients with AF. This article presents an analysis of three clinical cases of patients with complicated AF, discusses treatment from the standpoint of evidence-based medicine, the role of low adherence in the development of complications, and obstacles to increasing adherence.

Percutaneous left atrial appendage closure, a safe alternative to anticoagulation for patients with nonvalvular atrial fibrillation and end-stage renal disease on hemodialysis: A single center experience.

The evidence about the effectiveness and safety of oral anticoagulation in patients on hemodialysis is conflicting and scarce. Percutaneous left atrial appendage occlusion (LAAO) has demonstrated to be a valid alternative therapeutic option for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study is to present the outcomes of percutaneous LAAO in patients with end-stage renal disease (ESRD) on hemodialysis and NVAF in our center. We conducteda retrospective review of clinical records, demographics, LAAO procedure, complications, and outcomes of patients with NVAF and ESRD on hemodialysis who underwent a percutaneous LAAO in our center between January 2017 and January 2019. In the period of the study, eight patients with ESRD on hemodialysis underwent a percutaneous LAAO in our center. The overall mean age was 67.5years (range 56-81; SD±7.2). All patients had permanent NVAF. The total mean dialysis duration was 8.49years (range 0.83-14.8; SD±6.2). The mean CHA2DS2-VASc and HAS-BLED scores were high (4.75 [SD±1.16] and 4.62 [SD±0.91], respectively). All patients had history of a major hemorrhagic event (BARC Score ≥3). Most patients (n=6) showed left ventricular hypertrophy, and the average LVEF was 54% (SD±6.5). All devices were implanted successfully. Postprocedural antithrombotic regimen prescribed was based on antiplatelet therapy. No deaths, cardioembolic events, or major bleeding (according to the BARC scale) were reported during a mean follow-up of 14.24months (SD±9.44). Percutaneous LAAO could be of particular interest in patients with NVAF and CKD in hemodialysis. Further studies will be necessary to confirm this hypothesis.

P2529Efficacy and safety of oral anticoagulation in nonagenarian patients with atrial fibrillation

Abstract Introduction Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF. Methods We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission. Results The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097). Conclusions Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.