NOAC-treated Patients Research Articles

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non–Vitamin K Antagonist Oral Anticoagulant

BackgroundMost comparisons of bleeding patients who are taking warfarin or a non–vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. ObjectivesWe describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. MethodsWe conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. ResultsThe electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4–13.3) was associated with mortality. ConclusionsDespite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin.

317 Management and Outcomes of Major Bleeding Events in Patients Treated With Warfarin or a Non-vitamin K Antagonist Oral Anticoagulant

Over the last few years several non vitamin K antagonist oral anticoagulants (NOAC) have been approved by the FDA. However, there are little data on the management and outcomes of warfarin and NOAC-associated major bleeding outside the clinical trial setting. We compared the clinical characteristics, interventions and outcomes in patients with warfarin and NOAC-associated major bleeding presenting to the emergency department (ED). We conducted a structured, retrospective, observational study of non-valvular atrial fibrillation (NVAF), pulmonary embolism (PE), or deep venous thrombosis (DVT) warfarin or NOAC-treated patients presenting with major bleeding (according to the International Society of Thrombosis and Hemostasis) to a large, academic suburban ED between 1/2013-5/2015. Electronic medical record databases were searched cross-referencing medication lists and bleeding ICD-9 codes. The resulting charts were reviewed by a trained abstractor to yield confirmed NVAF, PE, or DVT patients with an index event of major bleeding and at least one dose of warfarin or one of 4 commercially available NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) in the five preceding days. Patient and clinical characteristics as well as treatments and outcomes were compared using Mann Whitney and X2 tests as appropriate. We hypothesized that mortality from intracranial hemorrhage (ICH) would be lower in NOAC-treated elderly patients. The electronic search yielded 95 cases of patients on a NOAC (dabigatran [33], rivaroxaban [32], abixaban [30]) and 349 patients on warfarin. The case fatality rate for ICH was lower in elderly patients treated with a NOAC compared to warfarin (4% versus 20%, OR [5.7, 95% CI, 0.7-45.5] P=0.046). Case fatality was similar for gastrointestinal bleeding (7% in both groups). Using age, sex, anticoagulant group, and site of bleeding as predictors, only ICH (Odds Ratio 3.1, 95% CI 1.6-6.1) and age (OR, 1.043 per year, 95% CI, 1.004-1.083) were associated with mortality. Despite rare use of reversal strategies, mortality was low and outcomes were favorable among patients with major bleeding while taking a NOAC. Mortality from ICH was lower in elderly patients on a NOAC versus warfarin.

Abstract 164: Specific Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry. Results (preliminary): Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p<0.001). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (>50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT. Conclusions: This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.

Abstract 17182: Patterns of Discontinuation for Non-vitamin K Oral Anticoagulants in Atrial Fibrillation: Results From the ORBIT-AF II Registry

Background: Oral anticoagulation (OAC) is effective at preventing stroke in patients with atrial fibrillation (AF), yet warfarin is often poorly tolerated. Non-vitamin K oral anticoagulants (NOACs) are as or more effective as warfarin, yet their tolerance and persistence in clinical practice is not known. Methods: We assessed patterns of persistent OAC use among 2,345 AF patients starting on therapy in the ORBIT-AF II registry (71% starting on a NOAC, and 29% on warfarin). Results: By 6 months, 364 (22%) patients started on a NOAC had discontinued or changed initial therapy versus 143 (21%) started on warfarin initially (p=0.5). Among warfarin users, patients who switched or discontinued therapy were of similar age (median ages 72 and 74 vs. 74 for stable users, p=0.7) and CHA2DS2-VASc scores (mean 98 and 3.66 vs. 3.84, p=0.4). Among NOAC users, those who discontinued treatment were younger (median age 68 vs. 73 for those who switched and 72 for stable users; p=0.0004), and lower CHA2DS2-VASc scores (3.02 vs. 3.58 and 3.47, respectively; p=0.0008). The median time to change or discontinuation was more rapid in those started on a NOAC vs warfarin (97 days vs. 122 days, p=0.003). Among those on warfarin at baseline, 7.6% (n=52) were switched to a NOAC within 6 months, whereas transitions from NOAC to warfarin was 2.5% (n=42).Transitions among NOACs occurred in 9.8%, 3.2%, and 5.5% of patients on baseline dabigatran, rivaroxaban, and apixaban, respectively. Physician preference was the most common reason for both OAC and warfarin changes (Table). Drug cost was the primary reason for change of therapy in 15% of NOAC users (vs. 0 for warfarin). Conclusions: At 6-month follow-up, one in five newly started on OAC had discontinued or changed. These rates of change were similar among warfarin and NOAC treated patients. Cost concerns drove discontinuation in a modest number of patients, however, cost concerns were more prevalent in NOAC-treated patients.

Reversal Strategies for NOACs: State of Development, Possible Clinical Applications and Future Perspectives.

The non-vitamin K antagonist oral anticoagulants (NOACs) are used for thromboembolic prophylaxis of patients with atrial fibrillation and in the treatment as well as secondary prophylaxis of patients with venous thromboembolism. Even though NOACs have a better safety profile than vitamin K antagonists (VKAs), there will still be bleeding complications on NOAC treatment. In some cases, stopping the NOAC and non-drug-related management such as manual compression and interventional endoscopy will be sufficient to stop the bleeding. In more serious bleeding events and before acute surgery, coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants including NOACs is currently undergoing phase II trials. For use of these specific antidotes, it is desirable that measurements for coagulation activity with a short response delay are widely available for the different NOACs and further research in this field is needed. Furthermore, guidelines for antidote use, including general measures for the treatment of NOAC-related bleeding, should be available.

Laboratory measurement of the non-vitamin K antagonist oral anticoagulants: selecting the optimal assay based on drug, assay availability, and clinical indication.

Although the non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine monitoring, there are special circumstances in which laboratory measurement may be warranted. The objectives of this review are to summarize evidence on the influence of the NOACs on coagulation tests and provide practical guidance to clinicians on measurement and interpretation of coagulation assays in NOAC-treated patients. Selection of an appropriate assay for NOAC measurement depends on the drug, clinical objective, and assay availability. Separate suggestions for assay selection are provided depending on whether specialized assays are available or whether choice is limited to conventional coagulation assays such as the prothrombin time (PT) and activated partial thromboplastin time (APTT). The dilute thrombin time (TT) and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal TT excludes clinically relevant levels. A normal APTT probably excludes excess levels of dabigatran, but does not rule out typical on-therapy drug concentrations. The PT is insufficiently sensitive to dabigatran to be useful in most situations. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal PT probably excludes excess levels of rivaroxaban and edoxaban, but not typical on-therapy levels of these agents. The PT is less sensitive to apixaban. Depending on the sensitivity of the thromboplastin reagent, a normal PT may not exclude excess levels of apixaban. The APTT has inadequate sensitivity to factor Xa inhibitors and is not recommended for their measurement.

Comparison of health-related quality of life among patients using novel oral anticoagulants or warfarin for non-valvular atrial fibrillation.

Objective:The aim of this study was to compare health-related quality of life (HRQoL) measures between novel oral anticoagulants (NOACs) and warfarin-treated Turkish patients who had been started on oral anticoagulants (OACs) due to non-valvular atrial fibrillation (AF) and to determine the effects of OACs on patient’s emotional status, anxiety and depression.Methods:A total of 182 patients older than 18 years with non-valvular AF and being treated with OACs for at least 6 months according to current AF guidelines who were admitted to outpatient clinics between July 2014 and January 2015 were included in this cross-sectional study. The exclusion criteria were receiving OACs for conditions other than non-valvular AF and being unable to answer the questionnaire. A questionnaire was administered to all participants to evaluate HRQoL, depression and anxiety. The mean differences between the groups were compared using Student’s t-test; the Mann–Whitney U test was applied for comparisons of the medians.Results:The annual number of hospital admissions was significantly higher in the warfarin group (p<0.001), and all HRQoL scores were significantly lower and Hospital Anxiety and Depression Scale (HADS) score was higher in the warfarin group (p<0.001). History of any type of bleeding was significantly higher in the warfarin group (p<0.001). However, none of the patients had major bleeding. Among patients who experienced bleeding, all HRQoL scores were significantly lower and HADS score was significantly higher (p<0.001 and p=0.002, respectively).Conclusion:Warfarin-treated patients had higher levels of self-reported symptoms of depression and anxiety and compromised HRQoL when compared with NOAC-treated patients. The results may be explained by higher rates of bleeding episodes and higher number of hospital admissions, which may cause restrictions in life while on warfarin treatment.

Non-vitamin K antagonist oral anticoagulants and major bleeding-related fatality in patients with atrial fibrillation and venous thromboembolism: a systematic review and meta-analysis

ObjectiveNon-vitamin K antagonist oral anticoagulants (NOACs) are efficacious and safe antithrombotic drugs but the non-availability of an antidote for potential fatal haemorrhagic events is clinically perceived as a strong limitation....

New oral anticoagulants versus vitamin K antagonists for treatment of acute venous thromboembolism: do they really increase the incidence of myocardial infarction?

Venous thromboembolism (VTE) is the third commonest cause of cardiovascular disease in the Western countries after coronary artery disease and stroke with 28 days mortality rate of 11 % for all VTE, and 25 % for cancerassociated VTE [1]. It is estimated that up to one-fifth of patients may have a fatal pulmonary embolism before diagnosis, or on the first day after diagnosis [2, 3]. The novel oral anticoagulants (NOACs), which include the direct thrombin inhibitor (DTI) dabigatran and the factor Xa inhibitors (FXaI) rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin for the treatment of acute VTE [4–10]. Loffredo et al. in this issue, have confirmed these findings in their recent meta-analysis of these RCTs, and showed similar rates of recurrent VTE and all-cause mortality, but significantly lower rates of major bleeding with NOACs as compared with warfarin [11]. Their findings are in keeping with other meta-analyses that have examined the efficacy and safety of NOACs for the treatment of acute VTE [12–17]. The authors also found that NOACs increased the risk of MI in this cohort. However, the estimates were not significant when analyzed separately according to the drug class: DTI [risk ratio (RR) 2.49; 95 % CI 0.82–7.55] and FXaI (RR 2.62; 95 % CI 0.82–8.39). Furthermore, these trials were not designed to compare the rates of MI in the NOACs and warfarin treatment arms, and MI was a secondary safety outcome. The majority of the included trials did not describe the baseline cardiovascular disease status and concomitant use of antiplatelet drugs [4–9]. Finally, the event rates for MI were relatively small in these trials. We agree with the authors that their finding of a ‘MI signal’ among NOAC-treated patients with VTE is hypothesisgenerating, but the overall question of an association between NOACs, in particular dabigatran, and MI is debatable. Our objective is to chart the course of this controversy, to summarize past and emerging data, and to discuss planned studies that, taken together, should inform readers about this issue. A possible association between NOACs and MI was first raised in the RE-LY trial, which showed that dabigatran 150 mg b.i.d. was associated with a higher risk for MI in patients with atrial fibrillation (AF) than warfarin [hazard ratio (HR) 1.38; 95 % CI 1.00–1.91). However, a re-analysis of the RE-LY trial that was supplemented by additional data, showed no significant increase in MI risk with dabigatran (RR 1.27; 95 % CI 0.94–1.71) [18], and no significant effect on fatal MI (HR 0.76; 95 % CI 0.31–1.89) [19]. More recently, several meta-analyses have assessed an association between DTIs and MI and, overall, provide conflicting results. Atang et al. in a meta-analysis of 11 trials, showed that DTIs (dabigatran, ximelagatran, and AZD0837) significantly increase MI risk [odds ratio (OR) 1.35; 95 % Cl 1.10–1.66] [20]. Mak showed a significant increase composite risk of unstable angina, MI or cardiac death with dabigatran as compared with either placebo, enoxaparin or warfarin (OR 1.30; 95 % CI 1.04–1.63) [21]. Loffredo et al. in a separate meta-analysis, found that, compared with warfarin, the MI rate was significantly & James Douketis jdouket@mcmaster.ca

Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants

BackgroundNon–vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. ObjectivesThis study’s objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. MethodsWe searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). ResultsWe identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R2 = 0.92 to 0.99) and ecarin-based assays (R2 = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R2 = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. ConclusionsDabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed.

Nationwide survey of catheter ablation for atrial fibrillation: The Japanese catheter ablation registry of atrial fibrillation (J-CARAF)–A report on periprocedural oral anticoagulants

BackgroundCatheter ablation has become an established therapy for the treatment of atrial fibrillation (AF). To obtain a perspective on the current status of this therapy in Japan, the Japanese Heart Rhythm Society (JHRS) conducted a nationwide survey, the Japanese Catheter Ablation Registry of Atrial Fibrillation (J-CARAF). In this study, we focused on whether periprocedural use of novel oral anticoagulants (NOACs) was related with excessive thromboembolic or bleeding complications. MethodsUsing an online questionnaire, JHRS requested electrophysiology centers in Japan to register the data of patients who underwent AF ablations in September 2011, March 2012, and September 2012. We compared the clinical profiles and ablation data, including the incidence of complications among patients in whom warfarin, a NOAC or neither was used as a periprocedural anticoagulant. ResultsA total of 179 centers submitted data relating to 3373 patients (62.2±10.6 years). Paroxysmal atrial fibrillation (PAF) was observed in 64.4% of patients. Warfarin, as a periprocedural oral anticoagulant, was used by 53.6% (1808/3373) of patients. A NOAC was given to 541 subjects (dabigatran: 504 [16.1%], rivaroxaban: 37 [1.1%]). In the remaining 1024 patients (30.4%), no periprocedural oral anticoagulants (OACs) were used. The proportion of PAF in warfarin-treated patients (61.1%) was significantly lower than that in NOAC-treated patients (70.1%, p<0.01) or in patients not treated with an OAC (67.4%, p<0.01). Patients treated with uninterrupted warfarin therapy were associated with significantly higher CHA2DS2-VASc scores. A total of 158 complications occurred in 151 subjects (4.5%). The incidence of complications in NOAC-treated patients (14/541 [2.6%]) was lower than that in patients receiving uninterrupted warfarin therapy (4.8%, p<0.05). The incidence of pericardial effusion in NOAC-treated patients (0.7%) was lower than in warfarin-treated patients (2.6%, p<0.05). The difference in the periprocedural anticoagulant strategy was not related to the frequency of other bleeding events. Cerebral infarction occurred in one patient from each patient group. ConclusionsOur results suggest that NOACs are safe for use as substitutes for warfarin without causing excessive increases in the rates of thromboembolic or bleeding complications.

Evaluation of Trends of Inpatient Hospitalisation for Significant Haemorrhage in Patients Anticoagulated for Atrial Fibrillation before and after the Release of Novel Anticoagulants

Compared to Vitamin K antagonists (VKA), novel oral anticoagulants (NOACs) appear to be safer in terms of major bleeding risks with added advantage of having fixed dosing schedules when used in patients with non-valvular atrial fibrillation (AF). We sought to study the differences as sources and severity of anticoagulant-associated haemorrhage in patients with AF in the year preceding introduction of NOACs (first cohort) as compared to post approval of the NOACs (second cohort) by retrospectively reviewing the hospital admissions, as well as the pharmacodynamic and pharmacokinetic interactions between time periods. There were 359 patients for the first cohort and 405 patients for the second cohort, including 57 patients prescribed NOACs. There was no significant difference in age, deaths, source of bleeding, or rate of pharmacokinetic or pharmacodynamic interaction between the two time periods. Comparing all VKA patients to patients prescribed NOAC's, there were non-significant but higher rates of intracerebral bleed, significantly higher rates of pharmacokinetic (194 (25.4%) versus 0 (0%), p<.001) and similar rates of pharmacodynamic interactions (505 (66.1%) versus 39 (68.4%), p=.70). Drug-renal interactions were seen in 7 of the 57 (12.3%) NOAC-treated patients, in which all seven had acute renal failure that may have prolonged the effects of the anticoagulants. NOACs hold promise in that drug interactions are far less common than those seen in VKAs, and intracerebral bleeds appear to be less common in randomised trials as well as our review. For patients on dabigatran or rivaroxaban, consideration should be given to serial monitoring of renal function.

Abstract W P223: Treatment of Cervical Artery Dissection with Different Antithrombotic Agents

Background and Purpose: Antiplatelet agents and anticoagulants are both accepted and commonly used agents for treatment of cervical artery dissection (CAD), though randomized clinical trials are lacking. We report on the use of novel oral anticoagulants for CAD and compared their efficacy and safety to traditional anticoagulants. Methods: We retrospectively identified patients diagnosed with CAD at a single academic center between July 2010 and December 2012. Patients treated with novel anticoagulants (NOAC: dabigatran or rivaroxaban), other anticoagulants (AC: warfarin, heparin, or low molecular weight heparin), or antiplatelet agents (AP: aspirin, clopidogrel, or aspirin-dypyridamole) were compared for baseline characteristics, recurrent stroke, vessel recanalization on follow-up, and bleeding complications using Fisher’s exact and student t-tests. Results: During the study period, 110 patients with CAD were included, of whom 20 (18%), 61 (55%), and 29 (26%) were treated initially with a NOAC, AC, and AP, respectively. Clinical follow-up was available in 98 (89.1%) patients while radiographic follow-up was available in 88 (80%) patients. NOAC-treated patients were more likely to have presented with ischemic stroke symptoms (90% vs. 55.7%, p=0.007) but had similar rates of severe stenosis (60% vs. 53.3%, p=0.522) and intraluminal/intramural thrombus (70% vs. 57.6%, p=0.327) on initial vascular imaging compared to AC patients. There was 1 recurrent stroke in the NOAC group and 1 in the AC group. Similar proportions of patients had resolved or improved stenosis on follow-up imaging (NOAC: 66.7 vs. AC: 63.3%, p=0.217). Hemorrhagic complications were more likely to occur in AC compared to NOAC patients (17.0% vs. 0%, p=0.019). Conclusion: In this retrospective study, use of novel oral anticoagulants for CAD was associated with similar rates of recurrent stroke and vessel recanalization on follow-up imaging but with fewer hemorrhagic complications. Given their safety profile, NOACs may be a reasonable alternative to traditional anticoagulants in CAD. Prospective validation of these findings is needed.

Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis

ObjectiveIn recent years, safety alerts have been made warning of the risk of serious drug-induced liver injury (DILI) caused by cardiovascular drugs. The new oral anticoagulants (NOACs) have now reached...

Oral anticoagulation therapy during catheter ablation for atrial fibrillation: J-CARAF registry

J-CARAF registry is a nationwide survey to reveal current status of atrial fibrillation (AF) ablation in Japan. This report assessed whether choice of the oral anticoagulation during AF ablation was associated with the incidence of ischemic stroke. Methods: Japanese Heart Rhythm Society (JHRS) requested electrophysiology centers in Japan to register the data of cases who undertook AF ablation in 2011 September, 2012 March, and 2012 September using questionnaire on the website. Results: One hundred and fifty-four centers reported data of 3373 AF ablation cases (age; 62.2±10.6 years, male; 76.1%, paroxysmal AF; 64.4%). CHA2DS2-VASc score was zero in 22.8% (n=770) or 1 in 27.7% (n=934). It was 2 or more in 1621 patients (48.1%). During the procedure of AF ablation, clinically effective warfarin was given in 1811 subjects (53,7%). Novel oral anticoagulants (NOAC) were used in 544 (16.1%). Among them, dabiagtran was used in 504, while 40 patients were taking rivaroxaban. The remaining 1018 patients undertook AF ablation without any oral anticoagulation therapy. Acute complications were observed in 168 patients (5.0%). Pericardial effusion was the most frequent event (n=75). In 29 patients, massive hematoma was noticed at the site of puncture. Clinically apparent ischemic stroke occurred in three patients. These patients were under treatment of warfarin (n=2: 0.11%) or dabigatran (n=1: 0.20%). MRI revealed new intracranial infarction in other six patients but without distinct neurological findings. Thus, intracranial ischemic event was noticed in 9 patients. Six of 9 were taking warfarin, and two were taking dabigatran. The incidence of these events was comparable between warfarin-treated and NOAC-treated patients (0.33% vs. 0.39%, not significant). These results suggest that warfarin and NOACs have no appreciable difference in the incidence of ischemic stroke related with AF ablation.

Review: family or couples therapy is more effective than non-family therapy for drug abuse

<h3>Objective</h3> In recent years, safety alerts have been made warning of the risk of serious drug-induced liver injury (DILI) caused by cardiovascular drugs. The new oral anticoagulants (NOACs) have now...