Warfarin-treated Group Research Articles

Systemic Embolism and Clinically Significant Bleeding Events in Older Adults with Nonvalvular Atrial Fibrillation After Treatment with Direct Oral Anticoagulants and Warfarin: A Retrospective Cohort Study in Japan

Background/Objectives: Anticoagulant therapy, particularly the use of direct oral anticoagulant agents (DOACs), is recommended for patients with nonvalvular atrial fibrillation (NVAF). This multicenter observational retrospective cohort study aimed to assess the efficacy and safety of DOACs compared to warfarin in Japanese patients aged 75 years and older with NVAF. Methods: Data from the Mie-Life Innovation Promotion Center Database were used to collect medical information on the patients. The cumulative incidences of clinically significant bleeding events and systemic embolic events (SEEs) were analyzed. Results: This study included 1787 older adult patients, of whom 1321 received DOACs (edoxaban: 428; apixaban: 586; dabigatran: 105; rivaroxaban: 202) and 466 receiving warfarin. There were no statistically significant differences in the cumulative incidence of bleeding events between the DOAC- and warfarin-treated groups. However, a statistically significant difference was observed for SEEs, with dabigatran showing a significantly lower incidence compared to warfarin. Conclusions: The incidence rates of bleeding events for individual DOACs were comparable to those for warfarin. Additionally, a history of vascular disorders was identified as a risk factor for bleeding events in the DOAC-treated group (hazard ratio (HR): 1.83, 95% confidence interval (CI): 1.16–2.88, p < 0.01) and warfarin-treated group (HR: 1.80, 95% CI: 1.15–2.84, p < 0.01). Based on real-world data, the overall efficacy and safety of DOACs were generally comparable to warfarin.

Randomized Comparison of Progression of Atherosclerotic Plaques and Calcification of Coronary Artery in Atrial Fibrillation Patients Treated With Edoxaban Versus Warfarin (The REPRESENT-AF trial)

Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.

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.

Comparison of the Safety and Efficacy of Warfarin Versus Rivaroxaban in Northern Chinese Patients with Different CHA2DS2-VASc Scores: A Retrospective Cohort Study

Purpose: This study was aimed at evaluating the safety and efficacy of warfarin versus rivaroxaban in patients with atrial fibrillation (AF) and different CHA2DS2-VASc score subgroups in northern China. Methods: A retrospective cohort study was conducted to evaluate 387 patients with AF who received treatment at our institution between September 2018 and August 2019. The patients were divided into two groups receiving either warfarin (n=194) or rivaroxaban (n=193). Follow-up data were collected, including adherence, bleeding and ischemic stroke events. Results: The group receiving rivaroxaban showed better adherence than the group receiving warfarin. In the warfarin-treated group, bleeding incidents declined with increasing scores. In the warfarin-treated group, patients with scores of 2–3 had greater adherence and fewer stroke occurrences. The events of bleeding and stroke did not significantly differ in patients in the rivaroxaban-treated group with different scores. Conclusions: Compared with patients in the warfarin group with different CHA2DS2-VASc scores, those in the rivaroxaban group had greater compliance, and fewer bleeding and stroke events. Regardless of economic considerations, rivaroxaban is preferable for anticoagulative AF treatment in northern Chinese patients.

Associations of Warfarin Use with Risks of Ischemic Cerebrovascular Events and Major Bleeding in Patients with Hyperthyroidism-Related Atrial Fibrillation.

The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and 168 hyperthyroidism-related AF patients with mean (SD) age of 59.9 ± 13.5 and 59.2 ± 14.6 in the warfarin-treated group and untreated group separately. The mean (SD) CHA2DS2-VASc scores for the two groups were 2.1 ± 1.6 and 1.8 ± 1.5, respectively. Patients with hyperthyroidism-related AF receiving warfarin had no significant risk of ischemic stroke/TIA (adjusted HR: 1.16, 95% confidence interval [CI]: 0.52-2.56, p = 0.717) compared to nonusers. There was a comparable risk of major bleeding between those receiving warfarin or not (adjusted HR: 0.91, 95% CI: 0.56-1.47, p = 0.702). The active-comparator design also demonstrated that warfarin use had no significant association with the risk of stroke/TIA versus aspirin use (adjusted HR: 2.43; 95% CI: 0.68-8.70). In conclusion, anticoagulation therapy did not have a statistically significant benefit on ischemic stroke/TIA nor risk of bleeding, among patients with new-onset hyperthyroidism-related AF under a low CHA2DS2-VASc score, by comparing those without use.

Direct oral anticoagulants versus warfarin in patients with antiphospholipid syndrome: A meta-analysis of randomized controlled trials.

This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome (APS). We performed a literature search using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. We also performed a meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness and safety of DOACs versus warfarin in patients with APS. Five RCTs involving 648 patients with APS (330 in DOAC-treated and 318 in control groups) were included in the meta-analysis. Among the patients included in the analysis, 29 (8.8%) patients experienced recurrent thrombosis in the DOAC treatment group, and 10 patients (3.1%) had thrombosis recurrence in the warfarin treatment group, resulting in a higher incidence in DOAC-treated than in the warfarin-treated groups [odds ratio (OR) = 2.163, 95% CI = 0.985-4.748, p = 0.055]. Incidence of arterial thrombosis was significantly higher in DOAC-treated patients than in warfarin-treated patients (OR = 5.168, 95% CI = 1.567-17.04, p = 0.007). Stroke and thrombosis occurrences were significantly higher in the triple positivity group than in the warfarin therapy group (OR = 12.03, 95% CI = 2.249-64.36, p = 0.004; OR = 2.940, 95% CI = 1.016-8.504, p = 0.047). However, venous thrombosis occurrences did not differ significantly between the DOAC-treated and warfarin-treated groups. There were no significant differences between the DOAC and warfarin groups in terms of any bleeding, major bleeding, minor bleeding, and all-cause mortality. DOACs were associated with higher rates of arterial thrombosis than warfarin in patients with APS, especially in the triple-positive group. However, a higher risk of recurrent venous thrombosis was not found in APS patients treated with DOACs compared to those treated with warfarin.

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study

Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis. Retrospective cohort study. Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring. Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses. Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and hypertrophic cardiomyopathy

Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.

Real-World Effectiveness and Safety of Apixaban versus Warfarin in Patients with Acute Venous Thromboembolism: Experience of a Large Tertiary Hospital in Saudi Arabia

PurposeThe main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a “real-world” setting.Patients and MethodsA retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up.ResultsAmong the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6±19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53–1.68), including DVT (AOR=1.06; 95% CI 0.52–2.17) and PE (AOR=0.78; 95% CI 0.31–1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04–0.83).ConclusionThe use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR

IntroductionCurrent guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center. MethodsPatients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups. ResultsNo significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized. ConclusionAdministration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.

Safety performance of rivaroxaban versus warfarin in patients with atrial fibrillation and advanced chro-nic kidney disease

Aim To evaluate safety of using rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or transient, stable decline of glomerular filtration rate (GFR) to 15-29 ml /min / 1.73 m2 in the presence of atrial fibrillation (AF).Material and methods This multicenter prospective, randomized study included patients admitted to cardiology departments from 2017 through 2019. Of 10 224 admitted patients 109 (3 %) patients with AF and stage 4 CKD or a stable decline of GFR to 15-29 ml /min / 1.73 m2 were randomized at 2:1 ratio to the rivaroxaban 15 mg /day (n=73) treatment group or to the warfarin treatment group (n=36). The primary endpoint was development of BARC and ISTH major, minor, and clinically relevant minor bleeding. Mean follow-up duration was 18 months.Results Patients receiving warfarin had a significantly higher incidence of BARC (n=26 (72.2 %) vs. n=31 (42.4 %), р&lt;0.01) and ISTH (n=22 (61.1 %) vs. n=27 (36.9 %), p&lt;0.01) minor bleeding and all ISTH clinically relevant (minor clinically relevant and major bleedings) n=10 (27.7 %) vs. n=8 (10.9 %), р=0.03]. The number of repeated hospitalizations was 65 (43% of patients) in the rivaroxaban treatment group and 27 (48% of patients) in the warfarin treatment group (р=0.57), including 24 (36.9 %) and 11 (40.7 %) emergency admissions in the rivaroxaban and warfarin treatment groups, respectively (р=0.96). Significant improvement of changes in creatinine clearance and GFR (by CKD-EPI and Cockroft-Gault) was observed in the rivaroxaban treatment group.Conclusion The study provided evidence for a more beneficial safety profile of rivaroxaban compared to warfarin in patients with AF and advanced CKD.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with antiphospholipid syndrome: a nationwide cohort study

Abstract Background and objectives Non-vitamin K antagonist oral anticoagulants (NOACs) are an effective and safe alternative to warfarin in atrial fibrillation (AF) patients, but there is not enough evidence that NOACs can offer sufficient protection in AF patients concomitantly diagnosed with antiphospholipid syndrome (APS). Use of rivaroxaban has been associated with an increased risk of thrombotic events compared with warfarin in results of the TRAPS trial, but the TRAPS trial is not for AF patients and included only very high-risk APS patients with triple-positive for all 3 antiphospholipid antibodies. We sought to compare thromboembolic events, bleeding, and mortality between NOAC and warfarin in patients with both AF and APS. Methods From the Korean National Health Insurance Service (NHIS) database during the period from January 1, 2011 to December 31, 2016, we identified an warfarin-treated group of patients with AF and APS (n=1,237) who were compared with a 1:1 propensity-matched NOAC treated group (n=1,237). Results After a median follow-up period of 17 months, NOAC-treated patients had lower incidence rates for ischemic stroke (5.9 and 10.5 events per 100 person-years for the NOAC and warfarin groups), major bleeding (4.1 and 8.3 events per 100 person-years, respectively), and all-cause mortality (3.4 and 15.6 events per 100 person-years, respectively) compared with warfarin in patients with AF and APS. Compared with warfarin, NOAC significantly decreased the risk of ischemic stroke (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.47–0.77, p&amp;lt;0.001), major bleeding (HR: 0.54, 95% CI: 0.41–0.72, p&amp;lt;0.001) and all-cause mortality (HR: 0.32, 95% CI: 0.27–0.40, p&amp;lt;0.001) with considering competing risk of death. Conclusions Compared with warfarin, AF patients with APS on NOACs had lower ischemic stroke, major bleeding, and all-cause mortality. Our data suggest that AF patients with APS can be safely and effectively treated with NOACs. Funding Acknowledgement Type of funding source: None

A Single-Center Retrospective Evaluation of the Use of Oral Factor Xa Inhibitors in Patients With Cerebral Venous Thrombosis.

Clinical practice guidelines recommend that cerebral venous thrombosis (CVT) be managed with long-term anticoagulant therapy using warfarin or low-molecular-weight heparin (LMWH) for 3 to 12 months. However, oral factor Xa inhibitors may offer preferable alternative treatment options for these patients. The primary objective was to determine the effectiveness and safety of rivaroxaban or apixaban compared with warfarin or enoxaparin as long-term anticoagulation therapy for patients with a new diagnosis of CVT. This was a single-center retrospective review of patients with newly diagnosed CVT who received acute and maintenance anticoagulation treatment. Study groups compared patients who received warfarin, enoxaparin, or an oral factor Xa inhibitor as their maintenance anticoagulant. The primary outcome was recurrent thrombotic events while on anticoagulation. Secondary outcomes included modified Rankin Scale, improved cerebral venous sinus opacification, duration of anticoagulant therapy, bleeding events during anticoagulant therapy, and adverse effects. A total of 119 patients were included in the analysis: warfarin (89), enoxaparin (11), and oral factor Xa inhibitor (19). The risk of recurrent thrombotic events were 11.2%, 0%, and 10.5% in the warfarin, enoxaparin, and oral factor Xa inhibitor treatment groups, respectively (P = 0.7635). There were no significant between-group differences observed regarding any of the secondary outcomes. Although the sample size is limited, these findings indicate that oral factor Xa inhibitors are a reasonable treatment option for patients with CVT. There was a trend toward more persistent symptoms in patients on warfarin, suggesting a potential improvement in recovery among patients that received an oral factor Xa inhibitor.

Efficacy and safety of new oral anticoagulants as part of triple antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome. Data from an observational study

Aim To study efficacy and safety of a triple antithrombotic therapy with direct oral anticoagulants (DOAC) versus warfarin in patients with atrial fibrillation after acute coronary syndrome, for 12 months following discharge from the hospital.Materials and methods This single-site cohort, prospective, observational study performed at the Regional Vascular Center 2 of the N.A. Semashko Nizhniy Novgorod Regional Clinical Hospital included 402 patients. It was possible to maintain contacts with 206 patients for 12 months. These patients were divided into two groups, the DOAC treatment (n=105) and the warfarin treatment (n=101) as a part of triple antithrombotic therapy upon discharge. Clinical observation was performed at 1, 3, 6, and 12 months after the discharge by structured telephone interview. Predetermined efficacy endpoints included cardiovascular death, myocardial infarction, stent thrombosis, and ischemic stroke. Safety endpoints included bleeding defined as small, medium (clinically significant), and major in accordance with the TIMI classification.Results At 12 months of follow-up, 80 patients (76.19%) continued taking DOAC and 39 patients (38.61%, p&lt;0.001) continued taking warfarin; in this process, only 25 patients (24.75%) monitored their INR on a regular basis. With a regular INR monitoring and TTR &gt;70%, death rate did not differ in the warfarin and the DOAC treatment groups. However, there was a difference in reaching the composite efficacy endpoint (p=0.048): ischemic events occurred statistically significantly more frequently in the warfarin treatment group than in the DOAC treatment group.Conclusions In 12 months after discharge from the hospital, compliance with the DOAC treatment as a part of the antithrombotic therapy was significantly higher than compliance with the warfarin treatment. The triple antithrombotic therapy with DOAC was safer than the warfarin treatment by the number of hemorrhagic complications and more effective in prevention of ischemic events, primarily due to no need for monitoring of lab test values.

Stroke Prevention in Patients with Atrial Fibrillation in Real Clinical Practice, Emphasis on Efficacy and Safety of Anticoagulant Therapy

Aim To evaluate frequency of administration of anticoagulant therapy (ACT) for atrial fibrillation and to study the effect of chronic antithrombotic therapy (ATT) on kidney function.Material and methods Due to a high medical and social significance of AF, much attention is presently paid to appropriate administration of ACT for AF in clinical practice. The study retrospectively analyzed 776 case reports of hospitalized patients with AF. The effect of chronic ATT on kidney function was studied in 70 patients who were rehospitalized, including 25 patients treated with warfarin, 25 patients treated with direct oral anticoagulants (DOAC), and 20 patients treated with acetylsalicylic acid (ASA).Results In January 2014, at the prehospital stage, 74.3 % of patients did not receive ATT, 14.7 % of patients received antiplatelet therapy, and only 11 % received anticoagulants. In the hospital in January 2014, ACTs were administered to 74.3 % of patients (warfarin, 58.6 %; DOAC, 15.7 %), 20.6 % of patients received antiplatelet drugs, and 5.1 % of patients were discharged without ATT. In January 2019, the number of patients receiving ACT at the prehospital stage increased to 58.1 % (warfarin, 13.8 %; DOAC, 44.3 %); 12 % of patients received antiplatelet drugs; and 29.9 % of patients did not receive ATT. The number of patients treated with warfarin and DOAC in the hospital increased to 14.8 % and 70.6 % (rivaroxaban, 33.4 %; apixaban, 25.5 %, and dabigatran, 11.7 %), respectively. The number of patients taking antiplatelet drugs decreased to 3.7 %, and the number of patients without ATT decreased to 10.9 %. There were no statistically significant differences in glomerular filtration rate (GFR) between these three groups at baseline. Only in the warfarin treatment group, GFR was significantly decreased from baseline during the follow-up period. Comparison of GFR in three study groups at the finale stage of the study showed significant differences between mean GFRs in the warfarin treatment group and the DOAC treatment group and between the warfarin treatment group and the ASA treatment group.Conclusion Among the prescribed and taken anticoagulants, DOACs are presently in the first place. Among DOACs, the most frequently prescribed drug is rivaroxaban. GFR decreases with the DOAC treatment slower than with the warfarin treatment. Despite the slower decrease in GFR with the ASA treatment compared to warfarin, ASA is not indicated for prevention of stroke in AF due to its low efficacy.

Evaluation of oral anticoagulants in atrial fibrillation patients over 80years of age with nonsevere frailty.

BackgroundThe safety and efficacy of an oral anticoagulant (OAC) treatment and the difference between direct OACs (DOACs) and warfarin in nonsevere frail elderly patients with AF are unclear.MethodsThis was a retrospective and observational study of 354 patients over 80 years of age with nonsevere frailty who were diagnosed with AF and treated with OACs. Nonsevere frailty was defined as a clinical frailty scale score of <7. Bleeding and thromboembolic events during the OAC treatment were followed up.ResultsOf 354 patients enrolled, 273 (77.1%) received DOACs and 81 (22.9%) received warfarin. Of 273 patients receiving DOACs, there were 210 (76.9%) prescribed with appropriate doses of DOACs. Of 81 warfarin‐treated patients, 53 (65.4%) were prescribed an appropriate dose of warfarin. During a follow‐up of 33.1 (14.0‐51.0) months, 15 patients (1.5/100 person‐years) had bleeding events and 10 (1.0/100 person‐years) had thromboembolic events while on an OAC treatment. The incidence ratio of bleeding events in patients receiving DOACs was lower than that in those receiving warfarin (1.0/100 person‐years vs 2.9/100 person‐years, hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.07‐0.91, P = .036). There was no significant difference in the incidence of thromboembolic events between the DOAC and warfarin treatment groups (0.88/100 person‐years vs 1.4/100 person‐years, HR: 0.63, 95% CI: 0.16‐2.57, P = .52).ConclusionsOACs are substantially safe and effective for preventing thromboembolic events in nonsevere frail patients over 80 years of age. Particularly, DOACs can be used more safely than warfarin.

Effectiveness of Nonvitamin K Antagonist Oral Anticoagulants and Warfarin for Preventing Further Cerebral Microbleeds in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation and At Least One Microbleed: CMB-NOW Multisite Pilot Trial

BackgroundNonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months. MethodsThis was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups. ResultsThe proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians’ discretion did not appear to alter the incidence of new CMBs. DiscussionThis is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

Heparin dosing in uninterrupted anticoagulation with dabigatran vs. warfarin in atrial fibrillation ablation: RE-CIRCUIT study.

AimsTo describe heparin dosing requirements in patients who underwent catheter ablation of atrial fibrillation with uninterrupted anticoagulation using dabigatran etexilate (dabigatran) or warfarin to attain therapeutic activated clotting time (ACT) in the RE-CIRCUIT® study. The RE-CIRCUIT study showed significantly fewer major bleeding events in the dabigatran vs. warfarin treatment group. Unfractionated heparin was administered during the procedure to maintain ACT >300 s.Methods and resultsPatients were randomly assigned to dabigatran 150 mg bid or international normalized ratio-adjusted warfarin. Ablation was performed with uninterrupted anticoagulation and continued for 8 weeks after the procedure. Heparin was administered after placement of femoral sheaths before or immediately after transseptal puncture. Ablation was performed in 635 patients (dabigatran, 317; warfarin, 318); data were available from 396 patients administered heparin (dabigatran, 191; warfarin, 205). Most frequent time window from last dose of study drug to septal puncture was 0 to <4 h in the dabigatran (41.3%) and 16 to <24 h in the warfarin arms (44.7%). Overall mean (standard deviation) heparin dose was similar between the dabigatran and warfarin groups [12 402 (10 721) vs. 11 910 (8359) IU, respectively]. Heparin dosing requirement to reach therapeutic ACT was lowest when time from last dose of dabigatran to septal puncture was 0 to <4 h.ConclusionPatients treated with dabigatran required a similar amount of unfractionated heparin as those treated with warfarin to achieve an ACT of >300 s during ablation. More heparin units were required when the time from the last dose of dabigatran to septal puncture increased.

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation With Hypertrophic Cardiomyopathy: A Nationwide Cohort Study

Chronic anticoagulation is recommended in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative to warfarin, but there are limited data to support their use in patients with HCM and AF. We sought to compare thromboembolic events, bleeding, and mortality between NOAC and warfarin in patients with HCM and AF. From the Korean National Health Insurance Service database during the period from January 1, 2011, to December 31, 2016, we identified a warfarin-treated group of patients with HCM and AF (n= 955) who were compared with a 1:2 propensity-matched NOAC treated group (n= 1,504). After a median follow-up of 16months, the incidence rates of ischemic stroke and major bleeding were similar between NOAC- and warfarin-treated patients with HCM and AF. NOAC-treated patients had lower incidence rates for all-cause mortality (5.11 and 10.13 events per 100 person-years for NOAC and warfarin groups) and the composite of fatal cardiovascular events (0.77 and 1.80 events per 100 person-years). Compared with warfarin, use of NOACs was associated with a significantly lower risk of all cause-mortality (hazard ratio, 0.43; 95%CI, 0.32-0.57) and composite fatal cardiovascular events (hazard ratio, 0.39; 95%CI, 0.18-0.82). Compared with warfarin, patients with HCM and AF on NOACs had similar stroke and major bleeding risks, but lower all-cause mortality and composite fatal cardiovascular events. Our data suggest that patients with HCM and AF can be safely and effectively treated with NOACs.

Measurement of Prothrombin Fragment 1+2 for the Assessment of Anticoagulant Activity in Patients Treated with Warfarin or Non-vitamin K Antagonist Oral Anticoagulant

[Background and purpose] Prothrombin fragment 1+2 (PF1+2) is a sensitive marker for blood coagulation system. In order to evaluate anticoagulant activity in patients treated with warfarin or non-vitamin K antagonist oral anticoagulant (NOAC), we measured plasma levels of PF1+2 and evaluated anticoagulant activity by each anticoagulant agent. [Methods] Subjects were 28 patients, 17 men and 11 women, 77±6 year old, with oral anticoagulant therapy for secondary prevention of stroke. We measured plasma levels of PF1+2 in 70 times in 7 patients treated with warfarin, and 154 times in 27 patients treated with NOAC. PT-INR was simultaneously measured in patients treated with warfarin. [Results] In warfarin treatment groups, PT-INR values were median 1.96 (IQR 1.8-2.1) and PF1+2 levels were median 111 pmol/l (IQR 95-141). All PF1+2 levels were below the upper limit of normal range, but 12 values (17%) of them in 5 patients were below the lower limit of normal range. 8 of the 12 values were at PT-INR below 2.5, and 1 of whom developed intracerebral hemorrhage. Plasma levels of PF1+2 in patients treated with dabigatran 150mg BID, dabigatran 110mg BID, rivaroxaban 15mg QD, rivaroxaban 10mg QD, apixaban 5mg BID, apixaban 2.5mg BID, and edxaban 30mg QD were median 116 pmol/l (IQR 99-136), 132 pmol/l (IQR 99-162), 109 pmol/l (IQR 100-125), 133 pmol/l (IQR 100-177), 88 pmol/l (IQR 76-102), 148 pmol/l (IQR 93-167), 221 pmol/l (IQR 208-234). They were all above the lower limit of the normal range, 3 of which were above the upper limit of the normal range. Excessive suppression of thrombin production was more frequently seen in warfarin treatment than in NOAC treatment (p<0.05). [Conclusion] In warfarin treatment, thrombin production was suppressed excessively in 17%, although it was not in NOAC treatment. (Received September 21, 2016; Accepted December 26, 2016; Published May 1, 2017).