Warfarin For Stroke Prevention Research Articles

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Compared with Warfarin in Patients with Low Bodyweight who have Atrial Fibrillation: ASystematic Review and Meta-analysis.

oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice for most clinical risks for which they are indicated. However, residual uncertainty remains regarding their use in preventing stroke in patients with low bodyweight [< 60 kg or body mass index (BMI) < 18 kg/m2]. We have carried out pooled systematic analyses of published studies to determine the efficacy and safety of these agents compared with warfarin in stroke prevention in patients with low bodyweight. We carried out a comprehensive search of electronic databases from inception to June 2023 for eligible studies reporting on the efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. These include PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness. Using the random effects model, derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes in patient cohorts exposed to direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. Nine studies (n = 159,514 patients) were included in our meta-analysis. DOAC analogs were associated with lower stroke recurrence compared with warfarin [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.49-0.9]; however, there was no significant difference in the composite outcome (OR 0.81, 95% CI 0.59-1.09) and mortality (OR 0.82, 95% CI 0.48-1.41). Additionally, DOAC analogs showed a significant reduction in major bleeding events by 30% compared with warfarin (OR 0.70, 95% CI 0.62-0.80). In this pooled meta-analytical synthesis of studies comprising both real-world and randomized controlled data, the use of DOAC analogs in patients with atrial fibrillation and low bodyweight (< 60 kg or BMI < 18 kg/m2) was associated with a significant reduction in risks of stroke and major bleeding compared with patient cohorts stabilized on warfarin-based therapy. There was uncertainty regarding the composite outcome and mortality point estimate between these two anticoagulation strategies. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it suggests the need for confirmatory non-inferiority randomized controlled trials evaluating DOACs versus warfarin in this cohort of patients.

Efficacy and safety of apixaban compared to warfarin for nonvalvular atrial fibrillation in end-stage renal disease on hemodialysis

BackgroundThis study compared the efficacy and safety of apixaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and end-stage renal disease (ESRD) on hemodialysis (HD). Apixaban decreased incidence of stroke and bleeding compared with warfarin in major clinical trials that excluded patients with severe renal dysfunction. Apixaban is no longer contraindicated in patients with ESRD on HD with NVAF based on pharmacokinetic studies. Limited clinical data exist for patients with ESRD on HD on apixaban. MethodsA retrospective chart review was performed on patients with a diagnosis of NVAF and ESRD on HD who were prescribed apixaban or warfarin for stroke prevention in the years 2018 through 2019. Patients’ charts were reviewed for up to a 2-year period. Patients on renal replacement therapy other than HD, those using anticoagulation for reasons other than NVAF, patients with Child-Pugh Class C cirrhosis, and those with severe mitral valve stenosis were excluded. The primary outcome was emergency department visits or hospital admissions for ischemic stroke or transient ischemic attack. Secondary outcomes included major or minor bleeding and adverse effects. ResultsA total of 181 patients were screened; 110 patients met eligibility criteria and were included in the analysis. Four patients (7.5%) in the apixaban group and 6 patients (10.5%) in the warfarin group met the primary outcome of hospitalization or emergency department visit for stroke (P = 0.742). Symptomatic bleeding occurred in 39.6% of patients in the apixaban group and 36.8% in the warfarin group (P = 0.918). A trend in major bleeding occurred more often in the warfarin group, 52.4% versus 49.2% (P = 0.758). ConclusionsThere were no statistically significant differences in efficacy and safety outcomes between apixaban and warfarin in patients with NVAF and ESRD on HD in the intention-to-treat analysis of our study. Larger trials are needed to further analyze this patient population.

Risk scores for major bleeding from direct oral anticoagulants: comparing predictive performance in patients with atrial fibrillation

BackgroundDespite direct oral anticoagulants (DOACs) being safer than warfarin for stroke prevention in atrial fibrillation (AF), major bleeding concerns persist. Most bleeding risk scores predate DOAC approval. ObjectivesThis study aimed to compare the Age, history of Bleeding, and non-bleeding related Hospitalisation [ABH] score’s performance—derived for DOAC-treated patients—with those of 5 other scores (Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA], Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly [HAS-BLED], Hepatic, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke [HEMORR2HAGES], Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF], and Congestive heart failure, Hypertension, Age ≥75 [doubled], Diabetes, Stroke [doubled]-Vascular disease, Age 65–74, Sex category [CHA2DS2-VASc]) in predicting DOAC-related major bleeding in patients with AF. MethodsIn this retrospective study of 2364 patients with nonvalvular AF on rivaroxaban or apixaban (median age, 68.3 years; 32.1% women), International Society on Thrombosis and Haemostasis–defined major bleeding (incidence, 4.1%; n = 97) was analyzed. C-statistics from time-dependent receiver operating characteristic (ROC) curves for continuous risk scores were the primary comparison metric, but other metrics, such as decision curves, were also compared. ResultsAt 100 days, C-statistics were highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60); some significant differences favored ORBIT-AF. At 1100 days, C-statistics remained highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60 again), and ORBIT-AF had significantly higher C-statistics than those for all other risk scores (P < .05), except for ATRIA. At 2100 days, all C-statistics were <0.60 with no significant differences. Decision curves showed the greatest net benefit for ORBIT-AF and ATRIA at 100 days and for ATRIA at 1100 days, with no discernible net benefit for any of the scores at 2100 days. ConclusionORBIT-AF and ATRIA provided the best bleeding risk prediction within the first 1100 days. None of the 6 bleeding risk scores provided predictive benefit over 2100 days of DOAC treatment.

Time-in-therapeutic-range defined warfarin and standard dose direct oral anticoagulants in atrial fibrillation: Ischemic stroke, intracranial hemorrhage and death in a nationwide registry study

Abstract Background and aims Direct oral anticoagulants (DOACs) have almost replaced warfarin in stroke prevention of patients with atrial fibrillation (AF). However, little is known whether DOACs are more efficacious or safer than warfarin having information on time-in-therapeutic-range (TTR) in the warfarin-treated patients. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients combining data from several Finnish health care registers. We analyzed all new-onset AF patients from 2011 to 2018 with available laboratory data. The rates of ischemic stroke (IS), intracranial hemorrhage (ICH) and mortality during oral anticoagulation (OAC) use were analyzed until maximum follow-up of 730 days. Confounding factors by baseline characteristics as well as medications were taken into account by an inverse probability of treatment weighted analysis. For warfarin users, TTR was calculated and patient quartiles by TTR were assigned. The rates of IS, ICH and mortality in TTR quartiles for warfarin users were compared to standard dose dabigatran (150 mg bd.), apixaban (5mg bd.) and rivaroxaban (20mg od.). Results Altogether, 73 469 new-onset AF patients with OAC therapy (50.4 % male, mean age 73.0 years, 43 548 on warfarin, with mean TTR 66% and median TTR 72%) were followed for 76 546 patient years (py). The rate of IS among patients with standard dose DOACs was 0.73/100 py for dabigatran (n=4 545)[HJK1] , 1.05/100 py for apixaban (n=12 426) and 0.83/100 py for rivaroxaban (n=12 950). In the TTR quartiles of patients on warfarin, rates of IS were 3.5, 1.8, 1.2 and 0.74/100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of IS were 1.3, 1.1 and 0.87/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.2, 1.7, 1.2 and 0.7/100 py. The respective rates of ICH were 0.47, 0.62 and 0.67/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.6, 0.99, 0.51 and 0.32/100 py. The weighted rates of ICH were 0.70, 0.65 and 0.73/100 py for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 3.4, 0.96, 0.51 and 0.30/100 py. For mortality, the raw incidence rates were 1.2, 2.8 and 2.1/100 py for for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 16.5, 5.3, 2.3, and 1.5/100 py. The weighted rates were 1.6, 2.9, and 2.6, for dabigatran, apixaban and rivaroxaban, and for warfarin from the lowest to the highest quartile: 14.6, 4.8, 2.0, and 1.3/100 py. The Figures provide cumulative incidence of IS and total mortality (crude rates) of the analyzed OAC groups. Conclusions The rates of IS, ICH and mortality were highest among patients on warfarin in the two lowest TTR quartiles, whereas the differences between high TTR groups and standard dose DOACs were only modest.Cumulative incidence of ischemic strokeCumulative mortality rate

Aging and anti-thrombotic treatment.

Several aging-related pathophysiological mechanisms have been described to contribute to the increased thrombotic risk in the elderly including oxidative stress, endothelial dysfunction, platelet and coagulation cascade activation. Antithrombotic treatment in the elderly should be individualized. Recent studies clarified some pathophysiological mechanisms of the enhanced oxidative stress and thrombotic alterations in older adults. In the last decade, randomized trials evaluated different antithrombotic strategies to reduce the risk of cardiovascular events in these patients. The proportion of elderly patients included in clinical trials is generally low, thus not reflecting the daily clinical practice. There is no consensus on the most appropriate antithrombotic treatment in elderly, also considering that bleeding risk management may be challenging in this high-risk subgroup of patients. Routine antiplatelet treatment is not a valid strategy for the primary prevention of cardiovascular events given the associated high risk of bleeding. In elderly patients with acute coronary syndrome, low-dose prasugrel or clopidogrel, shorter dual antiplatelet therapy and no pre-treatment before stent placement should be considered. Advanced age should not be the only reason for the underuse of oral anticoagulation in patients with atrial fibrillation, with direct oral anticoagulants to be preferred over warfarin for stroke prevention. Instead, a case-by-case clinical evaluation is warranted also based on patient's bleeding risk. There is a need for a structured tailored approach to manage thrombotic risk in elderly patients. The choice of the most appropriate antithrombotic treatment should balance efficacy and safety to reduce the risk of bleeding.

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Non-vitamin K Antagonist Oral Anticoagulant, Warfarin, and ABC Pathway Adherence on Hierarchical Outcomes: Win Ratio Analysis of the COOL-AF Registry.

Atrial fibrillation (AF) Better Care (ABC) pathway adherence is associated with improved outcomes. Clinical trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are as least as effective as warfarin for stroke prevention in AF patients. The Win Ratio method, analyzing hierarchical composite outcomes considering event timing and severity, has limited data on its use in Asians. We aim to apply Win Ratio in a registry to access the comparative effectiveness of NOACs versus warfarin and ABC adherence versus nonadherence in Asian patients with AF. Our study included nonvalvular AF patients from the nationwide prospective COOL-AF registry in Thailand. The NOAC-treated group was compared with the warfarin-treated group using the Win Ratio, with the following order: all-cause death, intracranial hemorrhage (ICH), ischemic stroke/transient ischemic attack/systemic embolism, non-ICH major bleeding, and myocardial infarction or heart failure. ABC pathway adherence versus nonadherence was also compared. A Win Ratio greater than 1.00 indicating a better outcome. The analysis included 2,568 patients, with 228 in the NOAC group and 2,340 in the warfarin group. The NOAC group had more wins than the warfarin group, with an unmatched Win Ratio of 1.64 (95% confidence interval [CI]: 1.22-2.20; p < 0.001). When compared with nonadherence, ABC pathway adherence was associated with a Win Ratio of 1.57 (95% CI: 1.33-1.85; p < 0.001). This Win Ratio analysis demonstrates the significant benefits of NOACs over warfarin and ABC pathway adherence over nonadherence in reducing the composite outcome in patients with AF.

Challenges of Anticoagulant Therapy in Atrial Fibrillation-Focus on Gastrointestinal Bleeding.

The rising prevalence and the complexity of atrial fibrillation (AF) pose major clinical challenges. Stroke prevention is accompanied by non-negligible risks, making anticoagulant treatment an ongoing challenge for the clinician. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in most AF patients, mainly due to the ease of their use. However, assessing the bleeding risk in patients receiving oral anticoagulants remains-particularly in the case of DOACs-highly challenging. Using dose-adjusted warfarin increases threefold the risk of gastrointestinal bleeding (GIB). Although the overall bleeding risk appears to be lower, the use of DOACs has been associated with an increased risk of GIB compared to warfarin. Accurate bleeding (including GIB-specific) risk scores specific for DOACs remain to be developed. Until then, the assessment of bleeding risk factors remains the only available tool, although the extent to which each of these factors contributes to the risk of bleeding is unknown. In this paper, we aim to provide a comprehensive review of the bleeding risk associated with oral anticoagulant therapy in AF patients, with a highlight on the latest insights into GIB associated with oral anticoagulation; we emphasize questions that remain to be answered; and we identify hotspots for future research.

Integrating Real-World Evidence in Economic Evaluation of Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation in a Developing Country.

This study aimed to estimate the cost effectiveness of non-vitamin K oral anticoagulants (NOACs) compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) in Thailand where suboptimal anticoagulation control is common. A hypothetical cohort of 65-year-old patients with NVAF and their disease progression was simulated in the Markov model. The following anticoagulant agents were used: warfarin, dabigatran, rivaroxaban, and apixaban. Warfarin with high, intermediate, and low time in therapeutic ranges (TTR) was used as the three different reference treatments. Baseline clinical events were obtained from a recently published real-world study in Thailand. A lifetime horizon was utilized in this model, and all analyses were performed from societal and healthcare perspectives. The results were reported as incremental cost-effectiveness ratios (ICERs) in 2021 US dollars per quality-adjusted life-year (QALY) gained. The sensitivity analyses were performed to assess the influence of parameter uncertainty. Apixaban was a cost-effective intervention compared with warfarin with low and intermediate TTR groups. In the low TTR group, the ICERs were $779 and $816 per QALY gained from the societal and healthcare perspectives, respectively, and in the intermediate TTR group, the ICERs were $2038 and $3159 per QALY gained from the societal and healthcare perspectives, respectively. Both ICERs were below the accepted willingness-to-pay threshold ($4806) in the context of Thailand's healthcare. In a developing country where suboptimal anticoagulation control is common, apixaban was the cost-effective alternative to warfarin for patients with both low and intermediate TTR control.

Anticoagulation for Stroke Prevention of Concomitant Atrial Fibrillation and End-Stage Renal Disease: Insights of Cardiologists and Nephrologists From India.

Introduction Patients with concomitant atrial fibrillation (AF) and end-stage renal disease (ESRD) are at increased risk of thrombosis and bleeding. Diligent anticoagulant therapy that prevents major bleeding is essential for stroke prevention. There is a dearth of evidence and guidance on anticoagulation in this patient subset. Methods A validated questionnaire was sent to 500 physicians across India. Anonymized responses from 353 consenting physicians (275 cardiologists and 78 nephrologists) were analyzed. Results Most physicians opined that the risk of progression of chronic kidney disease (CKD) stages 2-4 to ESRD was 1-5%, and that >10% of patients with ESRD had concomitant AF. Most physicians perceived that the risk of ischemic stroke, major bleeding, and mortality was 30-40%, <15%, and >40% respectively in patients with concomitant AF and ESRD. The first critical goal for the management of these patients was 'reduction of thrombotic risk', followed by 'prevention of bleeding' and finally 'prevention of ESRD progression' (72.0%, 68.0%, and 67.1% participants, respectively). Most participating physicians (93.8%) preferred non-vitamin K antagonist oral anticoagulants (NOACs) over warfarin for stroke prevention, and most of the participating physicians (94.9%) preferred an adjusted dose rather than the standard dose of the NOAC. Most of the responses were similar between cardiologists and nephrologists. Conclusion According to the survey response, patients with concomitant AF and ESRD have an increased risk of thrombosis, bleeding, and mortality. NOACs with dose adjustment are the preferred modality for stroke prevention among cardiologists and nephrologists in India, with the primary goal of preventing thrombotic events.

Trends in Oral Anticoagulant Use Among 436 864 Patients With Atrial Fibrillation in Community Practice, 2011 to 2020.

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA2DS2-VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health-system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health-system-level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%-54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high-risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient-level factors.

P73 Real-World Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) in Patients with Non-Valvular Atrial Fibrillation (NVAF): A Retrospective Cohort Study in Singapore

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly being used over warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. However, there are limited studies on clinical outcomes of NOAC in a multi-ethnic Asian country such as Singapore. This study aims to compare the real-world effectiveness and safety between NOAC and warfarin in NVAF patients and assess the potential long-term impact on the healthcare system in Singapore.

Comparative Effectiveness and Safety of Rivaroxaban and Warfarin for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation in an Omani Tertiary Care Hospital

Objective: The aim of the study was to compare the effectiveness and safety of rivaroxaban and warfarin as well as to determine the appropriateness of dosing and prescribing of rivaroxaban in Omani patients with non-valvular atrial fibrillation (NVAF). Methods: This retrospective cohort study was conducted using the Royal Hospital data registry. The study included all adults newly diagnosed with NVAF and treated with rivaroxaban or warfarin. The outcomes measured include ischaemic stroke, gastrointestinal bleeding (GIB), non-gastrointestinal bleeding (NGIB), as well as appropriateness of dosing and prescribing of rivaroxaban. Results: The analysis included 96 rivaroxaban users and 183 warfarin users; 51% of the cohort included males. There were no significant differences observed in the risk of ischaemic stroke between the two groups (hazard ratio (HR), 1.1; 95% confidence interval (CI): 0.4-3.4; p=0.8). However, those on rivaroxaban exhibited a significantly higher rate of GIB compared to those on warfarin (HR, 5.9; 95% CI: 2.9-11.7; p=0.001). There were no differences observed with regards to NGIB between the two groups (HR, 0.9; 95% CI: 0.4-1.9; p=0.8). Dosing and prescribing of rivaroxaban were found to be appropriate in 89% of the patients, with only 6% being prescribed an inappropriately lower dose. Conclusion: The study demonstrated no significant differences in the risk of ischaemic stroke or NGIB between rivaroxaban and warfarin groups in newly diagnosed NVAF patients. However, rivaroxaban users were found to have a significantly higher risk of GIB. Rivaroxaban was appropriately prescribed to the majority of the patients, and only a small proportion of the group received an inappropriately lower dose of rivaroxaban.

Cost-Utility Analysis of Dabigatran and Warfarin for Stroke Prevention Among Patients With Nonvalvular Atrial Fibrillation in India

ObjectivesDabigatran has a better safety profile and requires less monitoring, but is costlier than warfarin. This study evaluated the cost-utility of dabigatran relative to warfarin for preventing stroke in nonvalvular atrial fibrillation (NVAF) in India. MethodsA Markov decision analysis model was developed to compare dabigatran (110 or 150 mg twice a day) to warfarin titrated to target prothrombin time in patients with NVAF at high risk of stroke. Model utilities and transition probabilities were based on literature and costs on market prices. Data on out-of-pocket expenses and income lost were taken from a nationally representative survey. We adopted a societal perspective and discounted both costs and outcomes at 3%. Ischemic stroke, intracranial bleed, other major bleeds, and death were outcomes of NVAF. The model projected the costs, life-years, and quality-adjusted life-years (QALYs) for each intervention over a lifetime. We used gross domestic product per capita of India (US dollars [US$]1889) as the cost-effectiveness threshold. Sensitivity analyses were conducted. ResultsTreatment with either dose of dabigatran was associated with gain in life-years and QALYs compared with warfarin. The discounted incremental cost-effectiveness ratios/QALYs for both doses of dabigatran (110 mg US$7519; 150 mg US$6634) were above the cost-effectiveness threshold, and the probability of being cost-effective at this threshold was low. Cost of dabigatran was an important factor in determining incremental cost-effectiveness ratio. Price reduction of 150 mg dose by 49% will make it cost-effective. ConclusionsDabigatran is not cost-effective in the Indian societal context. Reducing the price of dabigatran 150 mg by half will make it cost-effective.

Cost utility analysis of dabigatran and warfarin for stroke prevention among patients with Non-Valvular Atrial Fibrillation in India (S12.005)

Cost utility analysis of dabigatran and warfarin for stroke prevention among patients with Non-Valvular Atrial Fibrillation in India (S12.005)

Severity and Hospitalization Cost Related to Warfarin-Related Adverse Events in a Tertiary Malaysian Hospital.

Introduction: Oral anticoagulant is essential for the treatment and prevention of thromboembolism. Warfarin is an effective oral anticoagulant in prevention and treatment of thromboembolism. However, warfarin is frequently associated with adverse event (AE) requiring hospitalization. Method: We performed a retrospective cohort study of all patients admitted to a large tertiary public hospital for warfarin-related AEs. Patients were grouped based on bleeding severity and the direct medical cost was also calculated. Results: During the 4 years study period, a total of 224 patients were admitted for warfarin-related AEs. Mean age of patients admitted was 65.1 years (standard deviation [SD] = 11.5). More than half, 59.6%, of them were on warfarin for prevention of stroke in atrial fibrillation or atrial flutter. Major bleeding occurred among 50.9% of the patients with gastrointestinal bleed, 34 (29.8%), as the common site of bleed. Patients with major bleed had longer median hospital stay of 4 days (interquartile range [IQR] = 5) compared to 3 (IQR = 3) days in non-major bleed. There were 17 (14.9%) death among the major bleeders. Mean medical cost for managing warfarin-related AEs was USD 708.08. Conclusion: The admitted patients were equally distributed in terms of bleeding severity. Medical cost incurred for managing warfarin-related AEs increased with the severity of bleeding.

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.

Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data. We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin. Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

Abstract 9740: Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Patients with Venous Thromboembolism or Nonvalvular Atrial Fibrillation and Chronic Kidney Disease a Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Direct oral anticoagulants (DOAC) have proven to be safe and effective alternatives to warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) as well as treatment of venous thromboembolism (VTE). Chronic kidney disease (CKD) is associated with increased risk of thromboembolism as well as bleeding. The objective of this research is to evaluate the efficacy and safety of DOAC compared to warfarin in patients with either VTE or NVAF across varying renal function. Methods: A systematic literature search using PubMed, Embase (1996 -November 2020), and Cochrane CENTRAL databases was conducted. Randomized controlled trials published in English between 1996 and November, 2020 evaluating the safety and efficacy of DOAC versus warfarin in patients with VTE or NVAF and CKD were included. Outcomes of interest were stroke or thromboembolic events, all-cause mortality, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB). Random effects-model was used for meta-analysis. Risk of bias was assessed by utilizing the Revised Cochrane risk-of-bias tool for randomized trials. Results: After screening and review, a total of 9 randomized controlled trials with 96,103 participants were included. Of those, 81.5% (n=78,361) had a specific classification of renal function throughout the study. Majority of participants had mild to normal (48.5%) renal function, and 35% had mild impairment and moderate and severe renal impairment accounted for 16% and &lt;1%, respectively. DOAC reduced risk of stroke or thromboembolic events compared to warfarin (RR 0.83, CI 95%: 0.77-0.89; p -value&lt;0.01), as well as all-cause mortality (RR 0.91, CI 95%: 0.85-0.97; p -value&lt;0.01). For safety outcomes, MB events were less likely to occur in DOAC group (RR 0.76, CI 95%: 0.69-0.84; p -value&lt;0.01). Whereas, no significant difference was found between DOAC and warfarin in CRNMB events (RR 0.90, CI 95%: 0.73-1.12; p- value 0.36). Conclusion: DOAC demonstrated better efficacy in preventing stroke or thromboembolic events and in decreasing all-cause mortality. DOAC also caused less MB events compared to warfarin. No difference in CRNMB events was detected between these agents.

Comparative effectiveness and safety of edoxaban vs warfarin in patients with atrial fibrillation: a nationwide cohort study

Abstract Background and purpose The effectiveness and safety of edoxaban 60 mg and 30 mg for stroke prevention compared with warfarin in patients with atrial fibrillation (AF) has not been well-described in a nationwide cohort of Caucasian patients treated in standard clinical practice. Methods We used Danish nationwide registries to identify patients with AF during June 2016 and November 2018 who were treated with edoxaban or warfarin and computed rates per 100 person-years of thromboembolic, all-cause mortality, and bleeding events using an inverse probability of treatment weighting approach to account for baseline confounding. We used weighted pooled logistic regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing events between edoxaban 60 mg and warfarin users; edoxaban 30 mg was not included in formal comparisons. Results We identified 6451 AF patients, mean age was 72 years and 40% were females. A total of 1772 patients were treated with edoxaban 60 mg, 537 with edoxaban 30 mg, and 4142 with warfarin. The median CHA2DS2-VASc score was similar between warfarin and edoxaban 60 mg with a score of 3 (interquartile range [IQR] 2–4). In the inverse probability of treatment-weighted pseudo-population, the thromboembolic event rate for edoxaban 60 mg was 0.95 and 1.0 for warfarin, corresponding weighted HR of 1.00 (95% confidence intervals [CI] 0.59, 1.71); see Figure. Edoxaban 60 mg users were associated with lower rates of all-cause mortality (3.93) compared to warfarin (6.04), with a HR of 0.64 (95% CI 0.47 to 0.88). The event rates for bleeding were 3.36 and 3.14, respectively; HR 1.09 (95% CI 0.77, 1.57) Conclusion Edoxaban 60 mg is a safe and effective treatment compared with warfarin for stroke prevention in routine clinical care for white European patients with AF, with non-significantly different risks for stroke and clinically relevant bleeding, but lower all-cause mortality. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Daiichi-Sankyo Europe GmbH. This funding source had no role in the design of this study, its execution, analyses, interpretation of the data, or decision to submit results.

Resuming anticoagulation in patients with atrial fibrillation experiencing intracranial hemorrhage.

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were <20 years old, who were not using OACs 6 months prior to ICH, or who had a CHA2DS2-VASc score of ≤1. We also excluded patients who died during admission for ICH, with follow-up for <6 weeks after discharge, or who started OAC >6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20–0.76) and IS/SE (HR = 0.12, 95% CI = 0.03–0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34–0.93) and IS/SE (HR = 0.26, 95% CI = 0.09–0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.