Warfarin For Atrial Fibrillation Research Articles

Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

A Comparison of Bleeding Events Among Patients on Apixaban, Rivaroxaban, and Warfarin for Atrial Fibrillation and/or Venous Thromboembolism

Introduction Apixaban and rivaroxaban are the most commonly used direct oral anticoagulants (DOACs) for atrial fibrillation (AF) and venous thromboembolism (VTE). Both have been compared to warfarin in landmark clinical trials. However, there are limited comparative efficacy data between these drugs in a real-world setting. We sought to assess patient characteristics and outcomes of apixaban, rivaroxaban, and warfarin in a non-trial based study cohort. Methods Retrospective registry-based cohort of adults starting apixaban, rivaroxaban, or warfarin therapy or switching between these anticoagulants for the indications of VTE and/or non-valvular AF. Through the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) collaborative of six anticoagulation clinics, warfarin treated patients were followed from January 2009 to June 2023. Four of these clinics contributed DOAC patient data from June 2011 to June 2023. Patients treated with other anticoagulants, with valvular AF, or with less than 3 months of follow-up were excluded. Propensity matched cohorts (apixaban versus warfarin [1:1], rivaroxaban versus warfarin [1:3], and apixaban versus rivaroxaban [1:1]) of patients were analyzed based on DOAC use at study enrollment, using 1:1-3:1 matching ratios. Patients were matched based on demographics, social history, comorbidities, medications, bleeding/thrombotic history, indication for anticoagulation, and follow-up. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room (ER) visits, hospitalizations, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results Of 13,435 patients on OAC who met the study inclusion criteria (3,536 on apixaban, 1,395 on rivaroxaban, and 8,504 on warfarin), the average age was 66.7 years (standard deviation [SD] 14.9 years), 51.1% identified as male, most (58.0%) were on anticoagulation for AF, and the average follow-up was 28.2 months (SD 30.7 months). After propensity matching, 3,527 patients on apixaban were compared to 3,527 patients on warfarin. Any bleeding was similar between groups, but major bleeding was higher with warfarin (3.4 versus 4.7 events/100 patient years, p&amp;lt;0.001). Thrombotic event rates were higher with apixaban (2.6 versus 2.1 events/100 patient years, p=0.026), including the thrombotic subtype of other thrombosis (1.0 versus 0.5 events/100 patient years, p&amp;lt;0.001). Rates of ER visits and hospitalizations for bleeding were higher with warfarin. Mortality was higher with warfarin (3.7 versus 4.4 deaths/100 patient years, p=0.027). After propensity matching, 1,395 patients on rivaroxaban were compared to 4,185 patients on warfarin. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 24.9 events/100 patient years, p&amp;lt;0.001; 4.7 versus 3.6 events/100 patient years, p=0.041 respectively). Thrombotic event rates were similar, aside from a higher rate of the thrombotic subtype of other thrombosis with rivaroxaban (1.0 versus 0.3 events/100 patient years, p=0.002). ER visits, hospitalizations, and mortality were similar between rivaroxaban and warfarin. After propensity matching, 1,395 patients on apixaban were compared to 1,395 patients on rivaroxaban. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 25.7 events/100 patient years, p&amp;lt;0.001; 4.7 versus 2.6 events/100 patient years, p&amp;lt;0.001). Thrombotic event rates were similar. ER visits occurred more frequently on rivaroxaban (12.8 versus 10.1 events/100 patient years, p=0.003) as did patient mortality (3.5 versus 2.6 deaths/100 patient years, p=0.047). Conclusions For patients on oral anticoagulation for AF and/or VTE we observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were higher with apixaban compared to warfarin, seemingly largely driven by “other” thrombotic events. Thrombotic event rates were otherwise similar between apixaban, rivaroxaban, and warfarin. We observed apixaban to be associated with lower mortality than rivaroxaban and warfarin. While these findings should be confirmed with randomized studies, they may have implications for anticoagulant selection.

Lower dose direct oral anticoagulation and warfarin in atrial fibrillation. Ischemic stroke, intracranial hemorrhage and mortality in a nationwide registry study

Abstract Background and aims Direct oral anticoagulants (DOACs) have replaced Vitamin-K antagonists as the primary choice of oral anticoagulation (OAC) in atrial fibrillation (AF). However, after several years of experience with DOACs, no studies have been made comparing the efficacy and safety of reduced dose DOACs and warfarin when the quality of warfarin treatment (time in the therapeutic range, TTR) information is available. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients combining data from several Finnish healthcare registers. We included all new-onset AF patients from 2011 to 2018 in Finland with purchases of either reduced dose DOAC or warfarin with eligible laboratory data. For patients on warfarin, we calculated TTR percentages and divided patients into TTR quartiles. Occurrence of ischemic stroke (IS), intracranial haemorrhage (ICH), or death during OAC use were recorded as outcomes during a maximum follow-up of 730 days. Crude and weighted rates of IS, ICH and mortality are provided. To minimize confounding by baseline characteristics and concomitant medications, an inverse probability of treatment weighted analysis was applied. Results A total of 52,022 new-onset AF patients with OAC therapy (46.1% male, mean age 75.7 years, 43 548 on warfarin) were followed for 56 382 patient-years (py). The rate of IS among patients was 1.63/100 py for dabigatran (n=2 672), 1.64/100 py for apixaban (n=3 936), 1.49 /100 py for rivaroxaban (n=1 866). For patients with warfarin, the rates of IS in TTR quartiles were 3.45, 1.79, 1.18 and 0.74/100 py from the lowest (mean TTR 32%) to the highest TTR quartile (mean TTR 90%). The weighted rates of IS were 1.34, 0.96 and 1.25/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.70, 1.87, 1.21 and 0.97/100 py. The rates of ICH were 0.68, 1.09 and 1.06/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.60, 0.99, 0.51 and 0.32/100 py. The weighted rates of ICH were 0.70, 0.70 and 0.90/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.80, 1.03, 0.54, 0.34 and 0.97/100 py. For mortality, raw incidences rates were 4.31, 11.40, and 8.11/100 py for for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 16.45, 5.33, 2.31, and 1.53/100 py. The weighted rates were 3.97, 7.97, and 6.78, for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 18.08, 5.86, 2.58, and 1.73/100 py. Figures portray cumulative IS incidence and mortality. Conclusion The incidence rates of all three outcomes were highest among patients on warfarin in the lowest TTR quartiles. For reduced dose DOAC patients, weighted IS rates were highest for those on dabigatran, ICH rates for those on rivaroxaban, and mortality rates for those on apixaban.Cumulative Incidence of Ischemic StrokeCumulative mortality

Comparative analysis of oral anticoagulation therapy in Asian patients with atrial fibrillation and end-stage renal disease: a nationwide population-based cohort study

Abstract Background The efficacy and safety of direct oral anticoagulants (DOACs) in patients with end-stage renal disease (ESRD) on dialysis is unclear. Although the RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation), a prematurely stopped randomized controlled trial, has been recently reported, the risks of clinical outcomes comparing DOAC and warfarin in pateints with AF and ESRD is still inconclusive. Purpose To analyze comparative effectiveness and safety of oral anticoagulant therapy including warfarin, rivaroxaban, apixaban, and edoxaban in Asian patients with AF and ESRD Methods Using a Korean nationwide claims database, anticoagulated patients with AF and ESRD between 2014 and 2020 were included. The occurrence of ischemic stroke, major bleeding, all-cause death, and the net clinical outcome (NCO, the composite of all clinical outcomes) were evaluated. We firstly compared between pooled DOAC and warfarin, and also compared each DOAC (rivaroxaban, apixaban, and edoxaban) to warfarin. Inverse probability of treatment weighting using propensity scores were used to balance difference in baseline characteristics of each group. Results A total of 5503 patients were included (3484 with warfarin, 407 with rivaroxaban, 1273 with apixaban, and 339 with edoxaban). During a median 1.4-year (interquartile ranges 0.5-3.0 years) of follow-up, 345, 376, 2321, and 2617 of ischemic stroke, major bleeding, all-cause death, and the NCO were occurred (incidence rate, 3.44, 3.77, 22.11, and 27.35 per 100 person-years, respectively). to warfarin, DOAC was associated with significantly lower risks of major bleeding (hazard ratio, 95% confidence interval: 1.159, 0.929-1.440, p=0.187), all-cause death (0.667, 0.520-0.847, p&amp;lt;0.001), and NCO (0.816, 0.748-0.889, p&amp;lt;0.001), with a comparable risk of ischemic stroke (1.159, 0.299-1.440, p=0.001) (Figure A). For the comparison between each DOAC and warfarin (Figure B), apixaban showed a comparable risk of ischemic stroke with warfarin, however, rivaroxaban and edoxaban were associated with a higher risk of ischemic stroke than warfarin. Among 3 DOACs, only apixaban associated with a lower risk of major bleeding than warfarin (0.600, 0.434-0.812, p=0.001). All DOACs were associated with a lower risk of all-cause death than warfarin. Overall, apixaban and rivaroxaban showed a significantly lower risk of NCO than warfarin (0.799, 0.719-0.887, p&amp;lt;0.001 for apixaban vs. warfarin; 0.842, 0.732-0.963, p=0.013 for rivaroxaban vs. warfarin). The results were consistent in a competing risk analysis. Conclusion In this large-scale observational cohort study, DOAC might be associated with a lower NCO than warfarin in Asians patients with AF and ESRD on dialysis. In line with current guidelines, apixaban and rivaroxaban could be a reasonable choice to achieve better net clinical benefit than warfarin in patients with AF and ESRD who are needed anticoagulation therapy.

Direct oral anticoagulation versus warfarin in atrial fibrillation: a nationwide cohort study of effectiveness and safety among frail patients

Abstract Background Frail patients with atrial fibrillation carry a high risk of both stroke and treatment-related bleeding complications, but evidence for the safety and effectiveness of anticoagulation regimens in frail patients remain sparse. Objectives To determine the comparative effectiveness and safety of DOAC versus warfarin in frail patients with atrial fibrillation. Methods A nationwide registry-based cohort study applying a new-user design including all frail patients with atrial fibrillation who redeemed a prescription for DOAC or warfarin between January 2012 and December 2020. We applied inverse probability of treatment weighting (IPTW) to account for baseline confounding and applied a marginal structural modelling approach with weighted pooled regression to compute hazard ratios (HR) and risk differences for thromboembolic events and major bleeding comparing specific DOAC doses with warfarin. Results We identified 32048 anticoagulation naïve frail patients (median age 80 years, 53% female) with atrial fibrillation who started anticoagulation treatment: 6747 (21.1%) patients initiated warfarin therapy, 17076 (50.3%) initiated standard dose DOAC, and 9179 (28.6%) patients with indication for dose reduction initiated reduced dose DOAC. The median CHA2DS2-VASc score was 5. The comparative effectiveness analyses showed a similar risk for thromboembolism with weighted HRs of 0.95 (95% CI 0.80-1.13) for standard dose DOAC versus warfarin, and 0.97 (95% CI 0.77-1.23) for reduced dose DOAC versus warfarin (see Table). The thromboembolic event free survival difference at one year was -0.2% for DOAC regardless of dosing when compared with warfarin. The comparative safety analyses revealed significantly lower risk of major bleeding among patients initiating standard dose (weighted HR 0.69, 95% CI 0.59-0.87) or reduced dose DOAC (weighted HR 0.67, 95% 0.55-0.81) when compared with warfarin. The risk difference of bleeding at one year for DOAC users varied between -1.3% and -3.0%, with the greatest difference for patients with high frailty level initiating reduced dose DOAC. Conclusion We observed similar risk of thromboembolism and significantly lower risk of major bleeding associated with both standard and reduced DOAC treatment regimens compared with warfarin in frail patients with atrial fibrillation in routine clinical practice.

Associations of anaemia with bleeding and thrombotic complications in patients with atrial fibrillation treated with warfarin: a registry-based nested case–control study

ObjectivesWe studied association of laboratory testing beyond the international normalised ratio (INR) with bleeding and stroke/transient ischaemic attack (TIA) outcomes in patients with atrial fibrillation treated with warfarin.DesignThis was a...

A case report of Spontaneous Spinal Epidural Hematoma in Elderly Patient with Surgical Decompression

Spontaneous spinal epidural hematoma (SSEH), uncommon disorder with potentially devastating consequences as high morbidity. Incidence around 0.1 in 100,000 per/year, male- female ratio is approximately 1.4:1, most cases in 4th-5th decades. The etiology was associated with lumbar puncture and myelography, arteriovenous malformations, bleeding disorders, pregnancy, spinal manipulation. Anticoagulation is also a risk factor for spontaneous spinal epidural hematomas, warfarin is the most common related with SSEH. SSEH present clinically as a cord compression syndrome, acute onset pain and neurological deficit such as progressive motor or sensory symptoms, sphincter dysfunction, ultimately leads to complete/incomplete motor deficit caused by spinal cord/nerve root compression or cauda equina. The symptoms depending on the location of the hematoma. The worst prognostic factors are thoracic location, anticoagulation, severe neurologic deficits on admission, sphincter dysfunction, rapid progression. Magnetic resonance imaging (MRI) is the gold standard technique to diagnose SSEH. Once the diagnosis is established with clinical and imaging results, early surgical intervention should be considered. Currently, appropriate management is emergence decompression laminectomy and hematoma evacuation. We present the case of 87-year-old female, on warfarin for atrial fibrillation. Without recent trauma events. Presented sudden thoracic and lumbar pain, paresthesias with irradiation to legs. Progression with sudden paraplegic and anesthesia in lower extremities. Thoracolumbar MRI revealed a posterior SSEH extended from T9-T12. Was released a laminectomy and SSEH aspiration within 6 hours from the symptom’s onset. The patient was discharged one week after the surgery, symptoms improved during the follow-up.

Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: Systematic Review and Meta-Analysis

BackgroundDirect-acting oral anticoagulants (DOACs) have demonstrated superior efficacy in preventing stroke and death compared with warfarin in patients with atrial fibrillation (AF), but their influence on dementia risk remains unclear. ObjectivesThe purpose of this study was to evaluate the relative risks of dementia in DOAC vs warfarin in patients with AF. MethodsAn electronic literature search was conducted to retrieve studies reporting comparisons of dementia incidence between patients treated with DOACs and warfarin for AF. HRs and 95% CI were pooled in a random-effects meta-analysis. Meta-regression was performed to identify prognostic baseline variables. Network meta-analysis was performed to determine dementia risk between individual DOACs and warfarin. ResultsTen studies (n = 342,624) were retrieved. DOAC was associated with a significantly lower risk of developing dementia compared with warfarin (HR: 0.88; 95% CI: 0.80-0.98; P = 0.017; I2 = 75%); significance was also seen in Asian patients (HR: 0.81; 95% CI: 0.68-0.86) but not non-Asian patients. Subgroup analyses of propensity score–matched studies and patients aged 65-75 years showed similar significance, but not for patients aged ≥75 years. Meta-regression found that a lower mean age corresponded to significantly greater favoring of DOAC over warfarin. Network meta-analysis found significant reductions in dementia risk over warfarin for rivaroxaban (HR: 0.854; 95% CI: 0.763-0.955), apixaban (HR: 0.881; 95% CI: 0.778-0.997), and dabigatran (HR: 0.871; 95% CI: 0.770-0.987); the highest-ranked treatment based on P scores was edoxaban. ConclusionsThe use of DOAC in AF significantly reduces dementia risk compared with warfarin, particularly in Asian patients. The possible reversal of this effect with increasing age merits further randomized trials with long-term follow-up. (Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: A Systematic Review and Meta-Analysis; CRD42022365634)

Systematic Review and Meta-Analysis of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation With Low Stroke Risk

Pivotal trials comparing direct oral anticoagulants (DOACs) against warfarin in patients with atrial fibrillation (AF) predominantly involved patients with high stroke risk. This study aimed to evaluate the efficacy and safety of DOAC versus warfarin in patients with low stroke risk. An online literature search was conducted to retrieve studies comparing clinical outcomes between patients treated with DOAC versus warfarin for AF, reporting outcomes for patients at low or minimal risk of stroke (CHA2DS2-VASc scores ranging from 0 to 2 or CHADS2 scores ranging from 0 to 1). The primary outcome was the occurrence of stroke or systemic embolism. Secondary outcomes included major bleeding, intracranial hemorrhage, and all-cause mortality. Hazard ratios for all outcomes were pooled in random-effects meta-analyses. A network meta-analysis of individual DOACs versus warfarin was also conducted. In total, 11 studies (132,980 patients) were included. DOAC was associated with a significantly lower risk of stroke or systemic embolism (hazard ratio0.85, 95% confidence interval0.75 to 0.96, p=0.008, I2=0%), major bleeding, intracranial hemorrhage, and mortality compared with warfarin. This benefit persisted even when study arms which had CHA2DS2-VASc scores of 2 were excluded. When restricted to 3 studies investigating only patients with a single nongender-related stroke risk factor, significant benefit was seen only for the outcome of major bleeding. In the network meta-analysis, only dabigatran was superior to warfarin for all 4 outcomes. In conclusion, DOACs should be the standard of care in low-risk patients with AF who require anticoagulation. In particular, dabigatran appears to have the best balance of stroke prevention and reduction in major bleeding.

Lower dose direct oral anticoagulation or warfarin in atrial fibrillation. Which one is the best when time on therapeutic range information is available?

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District (TYH2019309) and The Finnish Foundation for Cardiovascular Research Background and aims Elderly patients with atrial fibrillation (AF) and patients with renal failure – for example – are recommended to use reduced doses of direct oral anticoagulants (DOACs) to minimize risk of ischemic stroke and hemorrhagic complications. However, it is not known whether DOACs used with reduced doses are better than warfarin when the quality of warfarin treatment is available by means of time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. Here all new-onset AF patients from 2011 to 2018 on reduced dose DOAC in Finland and patients on warfarin with TTR data were analyzed. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC-use were analyzed until maximum follow-up of 730 days. Crude rates of stroke as well as weighted rates are provided. To avoid confounding by baseline characteristics as well as medications, an inverse probability of treatment weighted analysis was made. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Results Altogether, 52 204 new-onset AF patients with OAC therapy (46.1 % male, mean age 75.7 years, 43 549 on warfarin - with mean TTR 66%, median TTR 72%) were followed for 91 549 patient-years (py). Rate of stroke among patients on lower dose DOACs was 5.2/100 patient years (py) for dabigatran (n=2 672), 4.3/100 py for apixaban (n=3 936), 3.9 /100 py for rivaroxaban (n=1 866). In the TTR-quartiles of patients on warfarin, the rates of stroke were 9.3, 7.2, 5.5 and 4.3 /100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 5.1, 3.5 and 3.1/100 py for dabigatran, apixaban and rivaroxaban, respectively and for warfarin from the lowest to the highest quartile: 8.7, 7.0, 5.4 and 4.1/100 py. Figure provides survival probabilities of the OAC groups with confidence limits. Conclusion In AF patients treated with OAC, the rates of stroke were highest among patients on warfarin at the lowest TTR quartiles, while the differences between high TTR groups and lower dose DOACs were only modest.

Direct Oral Anticoagulants Would Be Best Choice for Atrial Fibrillation Patients After Coronary Stenting: Retrospective Study in a Japanese Population.

The combination of dual antiplatelet therapy (DAPT) plus warfarin in atrial fibrillation (AF) patients after coronary stenting has been reported to confer a significant risk of bleeding complications. Direct oral anticoagulants (DOAC) reduce the risk of stroke and bleeding complications in AF patients compared to warfarin. The optimal anticoagulation strategy for Japanese non-valvular AF patients after coronary stenting remains unclear. A total of 3230 patients who underwent coronary stenting were retrospectively reviewed. Of these, 284 cases (8.8%) were complicated by AF. Following coronary stenting, 222 patients received triple antithrombotic therapy (TAT) by DAPT plus oral anticoagulants; 121 patients received DAPT plus warfarin, and 101 patients received DAPT plus DOAC. We compared the clinical data between the two groups. The median International normalized ratio (INR) in the DAPT plus warfarin group was 1.61. Bleeding complications occurred in both groups. No cerebral infarction occurred in the DAPT plus DOAC group, while 4.1% of the DAPT plus warfarin group experienced cerebral infarction during follow-up (P=0.04). Twelve-month freedom from cerebral infarction, myocardial infarction, and cardiovascular death was significantly higher in the DAPT plus DOAC group than in the DAPT plus warfarin group [100% vs. 93.4%, P=0.009]. DOAC might be an optimal selection as an oral anticoagulant for Japanese AF patients who are receiving DAPT after PCI. A larger, longitudinal follow-up should be performed to clarify the clinical advantage of DOAC over warfarin, including among patients who receive single antiplatelet after coronary stent implantation.

The prevalence of using direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation at King Abdullah Medical City (KAMC) in Makkah, Saudi Arabia

The prevalence of using direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation at King Abdullah Medical City (KAMC) in Makkah, Saudi Arabia

Abstract 12361: Efficacy and Safety of NOACs vs. Warfarin Across the Continuous Range of Body Mass Index and Body Weight: Insights From COMBINE-AF

Introduction: The efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at the extremes of body mass index (BMI) and body weight (BW) remains uncertain, leading to concerns regarding use in these populations across clinical practice guidelines. Methods: This analysis of the COMBINE-AF database pools individual patient-level data from the 4 pivotal RCTs of NOAC vs. warfarin in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Pts randomized to low-dose NOACs not globally approved for clinical use were excluded. The primary efficacy and safety outcome was stroke/systemic embolic event (S/SEE) and major bleeding, respectively, with intracranial hemorrhage (ICH) being a secondary outcome. Outcomes were assessed across BMI and BW using a Cox model stratified by trial, with interaction testing for NOAC vs. warfarin. Restricted cubic splines were used to display the hazard ratio of NOAC vs. warfarin for each outcome across BMI. Results: For 58,464 pts, the median BMI was 28 (25 th -75 th %ile: 25-32) kg/m 2 , with the top 5% (n=2,924) having a BMI ≥ 40 kg/m 2 . For patients randomized to warfarin, the risk of each outcome was lower with increasing BMI (HR per 5 kg/m 2 increase: S/SEE 0.79 [95% CI 0.75-0.84]; major bleeding 0.91 [95% CI 0.87-0.95]; ICH 0.72 [95% CI 0.66-0.80]; p&lt;0.01 for each). There was no significant treatment interaction for NOAC vs. warfarin by BMI for S/SEE (p-interaction = 0.71; Fig 1A ), major bleeding (p-interaction = 0.15; Fig 1B ), or ICH (p-interaction = 0.84; Fig 1C ), such that there was consistent reduction in S/SEE and ICH ( Fig 1A and 1C, respectively ) across the range of BMI with NOAC vs. warfarin. Similar results were seen for each outcome when assessed by BW (median [25 th -75 th %ile]: 81 [70-94] kg; 5 th -95 th %ile: 55-119 kg). Conclusions: In this pooled analysis of the pivotal AF trials, use of NOAC was associated with a consistent reduction in S/SEE and ICH compared with warfarin across the range of BMI and BW.

DIRECT ORAL ANTICOAGULATION VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND BIOPROSTHETIC HEART VALVES: A RETROSPECTIVE, REAL WORLD COHORT STUDY

Data are limited on the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in atrial fibrillation (AF) patients with bioprosthetic heart valves, particularly in the real world. In this retrospective cohort study of consecutive patients with AF and surgical or transcatheter implantation of a bioprosthetic valve, we compared the efficacy and safety of DOACs and warfarin. The primary efficacy outcome was the composite of death and thrombosis (stroke, transient ischemic attack, systemic embolism, and myocardial infarction).

Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation

For some patients receiving warfarin, adding aspirin (acetylsalicylic acid) increases bleeding risk with unclear treatment benefit. Reducing excess aspirin use could be associated with improved clinical outcomes. To assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin. This pre-post observational quality improvement study was conducted from January 1, 2010, to December 31, 2019, at a 6-center quality improvement collaborative in Michigan among 6738 adults taking warfarin for atrial fibrillation and/or venous thromboembolism without an apparent indication for concomitant aspirin. Statistical analysis was conducted from November 26, 2020, to June 14, 2021. Primary care professionals for patients taking aspirin were asked whether an ongoing combination aspirin and warfarin treatment was indicated. If not, then aspirin was discontinued with the approval of the managing clinician. Outcomes were assessed before and after intervention for the primary analysis and before and after 24 months before the intervention (when rates of aspirin use first began to decrease) for the secondary analysis. Outcomes included the rate of aspirin use, bleeding, and thrombotic outcomes. An interrupted time series analysis assessed cumulative monthly event rates over time. A total of 6738 patients treated with warfarin (3160 men [46.9%]; mean [SD] age, 62.8 [16.2] years) were followed up for a median of 6.7 months (IQR, 3.2-19.3 months). Aspirin use decreased slightly from a baseline mean use of 29.4% (95% CI, 28.9%-29.9%) to 27.1% (95% CI, 26.1%-28.0%) during the 24 months before the intervention (P < .001 for slope before and after 24 months before the intervention) with an accelerated decrease after the intervention (mean aspirin use, 15.7%; 95% CI, 14.8%-16.8%; P = .001 for slope before and after intervention). In the primary analysis, the intervention was associated with a significant decrease in major bleeding events per month (preintervention, 0.31%; 95% CI, 0.27%-0.34%; postintervention, 0.21%; 95% CI, 0.14%-0.28%; P = .03 for difference in slope before and after intervention). No change was observed in mean percentage of patients having a thrombotic event from before to after the intervention (0.21% vs 0.24%; P = .34 for difference in slope). In the secondary analysis, reducing aspirin use (starting 24 months before the intervention) was associated with decreases in mean percentage of patients having any bleeding event (2.3% vs 1.5%; P = .02 for change in slope before and after 24 months before the intervention), mean percentage of patients having a major bleeding event (0.31% vs 0.25%; P = .001 for change in slope before and after 24 months before the intervention), and mean percentage of patients with an emergency department visit for bleeding (0.99% vs 0.67%; P = .04 for change in slope before and after 24 months before the intervention), with no change in mean percentage of patients with a thrombotic event (0.20% vs 0.23%; P = .36 for change in slope before and after 24 months before the intervention). This quality improvement intervention was associated with an acceleration of a preexisting decrease in aspirin use among patients taking warfarin for atrial fibrillation and/or venous thromboembolism without a clear indication for aspirin therapy. Reductions in aspirin use were associated with reduced bleeding. This study suggests that an anticoagulation clinic-based aspirin deimplementation intervention can improve guideline-concordant aspirin use.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair.

BackgroundWe sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement.Methods and ResultsTwo atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55–0.82], P<0.001), ischemic stroke (HR, 0.72 [95% CI, 0.52–1.00], P=0.05) and bleeding (HR, 0.79 [95% CI, 0.63–0.99], P=0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow‐up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86–1.01], P=0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13–1.43], P<0.001), and lower risk of bleeding (adjusted HR, 0.86 [95% CI, 0.80–0.93], P<0.001) compared with warfarin.ConclusionsIn patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.

Left atrial appendage occlusion should be offered only to select atrial fibrillation patients.

Left atrial appendage occlusion should be offered only to select atrial fibrillation patients.

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism.

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Effectiveness and safety of edoxaban in 27,333 patients from ETNA-AF with and without a history of intracranial haemorrhage after 2 years of treatment

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo, Inc. Medical writing and editorial support were provided by Atreju Lackey, PhD of AlphaBioCom, LLC, and funded by Daiichi Sankyo, Inc. Background/Introduction Once-daily edoxaban significantly reduced the risk of intracranial haemorrhage (ICH) compared with well-managed warfarin in atrial fibrillation (AF) patients in the ENGAGE AF-TIMI 48 trial. The effectiveness and safety of edoxaban in patients with prior ICH is unknown. Purpose To compare the effectiveness and safety of edoxaban in AF patients with or without a history of ICH. Methods The Global ETNA-AF programme is composed of and, thus, integrates data from multiple prospective, observational, and noninterventional regional studies collecting data of AF patients treated with edoxaban for stroke prevention. This snapshot analysis presents global and regional baseline characteristics with medical history and 2-year annualised rates of all-cause mortality, stroke (haemorrhagic, ischaemic, any), and bleeding (major bleeding [MB] including ICH, clinically relevant nonmajor bleeding [CRNMB], any bleeding), in patients with or without ICH history. Results Overall, 27,333 patients from Europe, Japan, South Korea, and Taiwan were analysed, including 367 with prior ICH and 26,966 without prior ICH. There were proportionally fewer patients with a history of ICH in the European population. Patients with a history of ICH were older (P=0.006), had a lower body mass index (P&amp;lt;0.0001), had a lower creatinine clearance (P=0.0001), and had more comorbidities, with a higher percentage of patients with a history of stroke, transient ischaemic attack (TIA), or MB (Table 1); the higher level of comorbidities noted in patients with a history of ICH was also reflected by higher baseline CHA2DS2-VASc and HAS-BLED scores (Table 1). Patients with a history of ICH were more likely receiving 30 mg edoxaban at baseline, whereas patients without ICH history were more often on 60 mg edoxaban (each P&amp;lt;0.0001). In patients with vs without ICH history, all-cause mortality (5.10% vs 3.14%; P=0.01), ischaemic stroke (1.79% vs 0.73%; P=0.006), and any stroke rates (3.25% vs 0.95%; P&amp;lt;0.0001) were higher (Table 2). Patients with vs without ICH history had higher annualised rates of MB (2.50% vs 1.00%; P=0.001), ICH (1.42% vs 0.27%; P&amp;lt;0.0001), haemorrhagic stroke (1.42% vs 0.20%; P&amp;lt;0.0001), CRNMB (2.49% vs 1.40%; P=0.04), and any bleeding (7.57% vs 4.27%; P=0.001), but these rates were low compared to other high-risk populations. ICH was not selected as a predictor of cardiovascular outcomes on multivariate prediction modelling. ICH had non-significant effects in predicting all-cause death (HR 1.22), ischemic stroke (HR 1.14), and major bleeding (HF 1.37) and repeat ICH (HR 1.94). Conclusions Patients with a history of ICH are a small, elderly, multimorbid subgroup of patients with AF. Treatment with the non-vitamin K antagonist oral anticoagulant edoxaban resulted in relatively low rates of major events.

Effectiveness and Safety of DOACs in Atrial Fibrillation Patients Undergoing Catheter Ablation: Results from the China Atrial Fibrillation (China-AF) Registry.

Direct oral anticoagulants (DOACs) have increasingly become an alternative to warfarin in atrial fibrillation (AF) patients. Nonetheless, data on the effectiveness and safety of DOACs in periprocedural of catheter ablation (CA) in real-world practice was relatively rare. 3385 AF patients underwent initial CA and never used oral anticoagulant before enrollment between April 2013 and December 2018 were involved from China Atrial Fibrillation (China-AF) Registry. Warfarin, rivaroxaban and dabigatran were used in 1896 (56.0%), 718 (21.2%), and 771 (22.8%) patients, respectively. Propensity score matching was used to balance covariates across study groups. No significant differences were observed in rivaroxaban-warfarin, dabigatran-warfarin and dabigatran-rivaroxaban cohort for thromboembolic (TE) and major bleeding (MB) incidence. Similar results were also revealed in low-dose rivaroxaban (RLD)-warfarin, low-dose dabigatran (DLD)-warfarin and DLD-RLD cohort. However, the risk of non-MB was higher not only on standard-dose of rivaroxaban but also on RLD when compared with warfarin and with DLD, respectively. In this study, the incidence of TE and MB were both comparable in standard- or low-dose DOACs versus warfarin and between the two DOACs, whereas the risk of non-MB was higher in rivaroxaban than in warfarin and in RLD than in DLD.