Dabigatran for periprocedural anticoagulation following radiofrequency ablation for atrial fibrillation: a meta-analysis of observational studies

Purpose

Dabigatran is approved for prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). The safety and effectiveness of periprocedural dabigatran in ablation for AF are unknown.

Methods

We performed a meta-analysis of all studies comparing periprocedural dabigatran with warfarin for anticoagulation in AF ablation. Studies of >100 patients with post-procedure follow-up were included. Outcomes were compared by calculating maximum likelihood estimates with confidence intervals. The co-primary endpoints were neurological events and major bleeding.

Results

Ten cohort studies were included, including a total of 1,501 patients receiving dabigatran and 2,356 receiving warfarin. The mean age was 59–64 years and inclusion of women varied (10–33 %). Intra-procedural unfractionated heparin and irrigated ablation catheters were used routinely. Adverse events were low overall; however, the dabigatran group demonstrated a numerical excess of neurological events (10/1,501 [0.7 %] versus 4/2,356 [0.2 %]), but equivalent major bleeding outcomes (24/1,501 [1.6 %] versus 40/2,356 [1.7 %]). In the meta-analysis, there was a nonsignificant trend towards higher rates of the composite primary endpoints (any neurological event or major bleeding) in the dabigatran group. Dabigatran demonstrated a significantly higher rate of neurological events (estimated absolute risk difference 0.0047, 95 % confidence interval 0.0007 to 0.0099).

Conclusions

Compared with warfarin, dabigatran may be associated with a higher frequency of periprocedural neurological events following radiofrequency ablation of AF. Randomized clinical trials are needed to definitively assess the safety and efficacy of novel oral anticoagulant use for periprocedural anticoagulation for ablation of AF.     

Continuous warfarin versus periprocedural dabigatran to reduce stroke and systemic embolism in patients undergoing catheter ablation for atrial fibrillation or left atrial flutter

Purpose

Left atrial catheter ablation for patients with atrial fibrillation (AF) requires periprocedural anticoagulation to minimize thromboembolic complications. High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported, raising concerns regarding its safety during left atrial catheter ablation. We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin, at a single high-volume AF ablation center.

Methods

We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at Vanderbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months. Patient cohorts were divided into two groups, those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on dose-adjusted warfarin, with or without low-molecular-weight heparin bridging. Dabigatran was held 24–30 h pre-procedure and restarted 4–6 h after hemostasis was achieved. We evaluated all thromboembolic and bleeding complications at 3 months post-ablation.

Results

A total of 254 patients underwent left atrial catheter ablation for atrial fibrillation or left atrial flutter. Periprocedural anticoagulation utilized dabigatran in 122 patients and warfarin in 135 patients. Three late thromboembolic complications occurred in the dabigatran group (2.5 %), compared with one (0.7 %) in the warfarin group (p?=?0.28). The dabigatran group had similar minor bleeding (2.5 vs. 7.4 %, p?=?0.07), major bleeding (1.6 vs. 0.7 %, p?=?0.51), and composite of bleeding and thromboembolic complications (6.6 vs. 8.9 %, p?=?0.49) when compared to warfarin. There were no acute thromboembolic complications in either group (<24 h post-ablation).

Conclusions

In patients undergoing left atrial catheter ablation for AF or left atrial flutter, use of periprocedural dabigatran etexilate provides a safe and effective anticoagulation strategy compared to warfarin. A prospective randomized study is warranted.     

Dabigatran in atrial fibrillation: pharmacology and clinical trials

The central pharmacologic approach to stroke prevention in atrial fibrillation has recently changed with the approval of dabigatran by the US Food and Drug Administration (FDA). Dabigatran is an oral anticoagulant that belongs to the class of direct thrombin inhibitors. Dabigatran has predictable pharmacokinetics, without significant drug and food interactions, rapid onset, and requires twice-daily administration without the need for monitoring. The only drug contraindicated with dabigatran is rifampin. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, dabigatran at a dose of 150 mg bid is statistically superior to warfarin in preventing strokes and systemic embolism in patients with atrial fibrillation and has a lower non-statistically significant rate of major bleeding. There is significantly lower rate of intracranial bleeding. The FDA recently approved the 150-mg bid dose for patients with a creatinine clearance above 30 mL/min and 75 mg bid for use in patients with a creatinine clearance of 15 to 30 mL/min. A prespecified subanalysis in both warfarin-experienced and warfarin-naive subgroups mirrored the main results. For cardioversions, a post hoc analysis showed that the rate of thromboembolism and major bleeding within 30 days of cardioversion for dabigatran 150 mg bid was low and comparable to that of warfarin, with or without transesophageal echocardiography guidance. Dabigatran, therefore, is the first novel anticoagulant to offer an alternative to warfarin.     

Dabigatran in the peri-procedural period for radiofrequency ablation of atrial fibrillation: efficacy, safety, and impact on duration of hospital stay

Purpose

Dabigatran is effective for both the prevention of stroke and bleeding in patients with atrial fibrillation (AF). However, the safety and efficacy of the use of dabigatran in the peri-procedural period for radiofrequency catheter ablation (RFCA) of AF is unknown. Therefore, the purpose of this study was to evaluate the safety and efficacy of dabigatran in the peri-procedural period for RFCA of AF and the duration of hospital stay.

Methods

Consecutive patients (n?=?227) who underwent RFCA for AF were prospectively analyzed. Peri-procedural anticoagulant therapy with dabigatran (n?=?101, D group) was compared with warfarin and heparin bridging (n?=?126, W group). Dabigatran was discontinued 12–24 h before and restarted 3 h after the procedure. Warfarin was stopped 3 days before the procedure and unfractionated heparin was administered.

Results

Ischemic stroke occurred in one patient of the D group (0.8 %). There was no significant difference between the two groups in the incidence of major bleeding (three cases of cardiac tamponade in each group and one case of intracranial bleeding in the W group, p?=?0.93) or minor bleeding (five cases in the D group vs. five in the W group, p?=?0.54). The duration of hospital stay was significantly shorter in the D group than in the W group (7.2 vs. 10.3 days, p?=?0.0001).

Conclusions

Peri-procedural anticoagulation therapy with dabigatran for RFCA of AF was equally safe and effective compared with warfarin and heparin bridging. The use of dabigatran for RFCA of AF shortened the duration of hospital stay.     

Dabigatran Compared With Warfarin for Stroke Prevention With Atrial Fibrillation: Experience in Hong Kong

Background:

Dabigatran is an oral direct thrombin inhibitor recently approved for stroke prevention in atrial fibrillation (AF) as an alternative to warfarin. The primary advantages of dabigatran are freedom from monitoring and less interaction with other drugs and food. It is ideal for patients who are unwilling to adhere to regular coagulation monitoring or whose therapeutic effect using warfarin is not optimal despite adequate monitoring and management. However, the impact of dabigatran on health‐related quality of life (HRQoL) and drug compliance has been less evaluated. This study aimed to evaluate the clinical and humanistic outcomes of dabigatran use in Hong Kong.

Hypothesis:

Dabigatran 110 mg twice daily was non‐inferior in stroke prophylaxis in AF patients compared to adjusted‐dose warfarin; while dabigatran 150 mg twice daily was superior to adjusted‐dose warfarin in the real world data in Hong Kong.

Methods:

We retrospectively analyzed 244 patients with newly diagnosed AF and prescribed dabigatran (n = 122) or warfarin (n = 122) for stroke prophylaxis from the Prince of Wales Hospital between January 2010 to November 2011. Clinical outcomes including death, stroke, bleeding, and HRQoL using the EuroQol EQ‐5D‐5L were compared between patients on dabigatran and warfarin.

Results:

The median duration of follow‐up was 310 days. Stroke occurred in 2 patients (1.64%) in the dabigatran group and 4 in the warfarin group (3.28%) (adjusted hazard ratio [HR]: 0.53, P = 0.47). Bleeding of any degree occurred in 28 patients on dabigatran and 38 patients on warfarin (adjusted HR: 0.76, P = 0.28), with age over 70 years and renal impairment being significant positive predictors of bleeding (P = 0.01 and 0.02, respectively). Dyspepsia was the most common adverse event of dabigatran over warfarin (19.7% vs 8.2%, P = 0.01). Rate of discontinuation of dabigatran was 25.4%, with dyspepsia being the most common cause for discontinuation (6 patients, 4.92%). There was no significant difference in drug compliance or HRQoL at 1 year between the 2 groups (utility score 0.77 [dabigatran] vs 0.74 [warfarin], P = 0.28). Conclusions: In Hong Kong, the clinical efficacy and safety of dabigatran were comparable to that of warfarin, and drug compliance and HRQoL of using dabigatran and warfarin were similar after 1 year of use. Clin. Cardiol. 2012 DOI: 10.1002/clc.22069 This study was supported by the School of Pharmacy, The Chinese University of Hong Kong. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Renal Function and Outcomes With Dabigatran Dual Antithrombotic Therapy in Atrial Fibrillation Patients After PCI

ObjectivesThe study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BackgroundThe RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events.MethodsRisk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and ≥80 ml/min.ResultsCompared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl ≥80 ml/min (p for interaction = 0.02).ConclusionsIn the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.     

Safety and Efficacy of Dabigatran Compared With Warfarin for Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-analysis

Background

The safety and efficacy of dabigatran in the periprocedural period for patients undergoing atrial fibrillation ablation is not well established. We conducted a meta-analysis of the periprocedural use of dabigatran vs warfarin (with or without heparin bridging).

Methods

A literature search was performed using multiple databases. Outcomes were (1) major bleeding; (2) minor bleeding; and (3) thromboembolic events. Odds ratios (ORs) were reported for dichotomous variables.

Results

Eleven controlled studies (9 cohorts, 1 randomized controlled trial and 1 case-control study; 3841 patients) were identified. Dabigatran was used in 1463 patients, uninterrupted in 223 and held up to 36 hours in the remainder. No significant differences were noted in major bleeding rates between dabigatran and warfarin groups (1.9% vs 1.6%; OR, 1.04 [95% confidence interval (CI), 0.51-2.13]; P = 0.92). Cardiac tamponade was observed in 1.4% in dabigatran vs 1.1% in warfarin groups (OR, 1.1; 95% CI, 0.55-2.11; P = 0.82). Similar rates for dabigatran vs warfarin were reported for minor bleeding (3.8% vs 4.5%; OR, 0.85; 95% CI, 0.58-1.25; P = 0.40), hematoma (2% vs 2.7%; OR, 0.67; 95% CI, 0.41-1.08; P = 0.1), and thromboembolic events (0.6% vs 0.1%; OR, 2.51; 95% CI, 0.78-8.11; P = 0.12).

Conclusions

This meta-analysis suggests that dabigatran and warfarin have similar safety and efficacy overall for periprocedural anticoagulation in patients undergoing radiofrequency atrial fibrillation ablation. Signals were seen favouring dabigatran (for hematomas) and warfarin (for thromboembolic events), but neither was statistically significant because of low event rates. More high-quality data are required to definitively compare the 2 strategies.     

Switching of Oral Anticoagulation Therapy After PCI in Patients With Atrial Fibrillation: The RE-DUAL PCI Trial Subanalysis

ObjectivesThe aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y₁₂ inhibitor) versus warfarin triple therapy (warfarin plus a P2Y₁₂ inhibitor plus aspirin) in patients with atrial fibrillation who underwent percutaneous coronary intervention (PCI).BackgroundIn the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI.MethodsA total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive.ResultsRisk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups.ConclusionsBleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.     

A real world data of dabigatran etexilate: multicenter registry of oral anticoagulants in nonvalvular atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.004). Dyspepsia was significantly higher in both DE doses than warfarin (p = 0.004) Both DE doses are as effective as warfarin in reducing stroke rates in NVAF patients, without increasing MI rates. Intracranial bleeding rates are significantly lower in warfarin than both doses of DE and gastrointestinal bleeding risk increases with increased DE doses.     

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

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

利伐沙班用于心房颤动导管消融术后抗凝治疗有效性及安全性

目的 评估利伐沙班用于心房颤动导管消融术后抗凝治疗的有效性及安全性。方法 将接受房颤射频导管消融的患者分为利伐沙班组(57例)和华法林组(100例)。利伐沙班组:房颤导管消融术后给予10 mg,2次/d或20 mg,1次/d口服,服用1个月后根据不同临床情况调整剂量,给予10 mg 1次/d或20 mg 1次/d再服用1个月。华法林组:房颤导管消融术后给予华法林3~6 mg/d,根据国际标准化比值(INR)调整剂量,控制INR在2.0~3.0,共服用2个月。所有患者从抗凝开始到抗凝结束选用同一种抗凝药物。结果 基线水平的比较除性别外其他指标均无统计学差异。两组有效性及安全性比较:华法林组和利伐沙班组均未发生血栓栓塞事件(死亡、脑栓塞、肺栓塞、体循环栓塞)。两组均无大出血事件发生;不明显出血事件利伐沙班组为5%(3/57)、华法林组为11%(11/100),差异无统计学意义。结论 口服利伐沙班用于血栓栓塞低、中危房颤患者导管消融术后抗凝安全有效。     

Total atrioventricular nodal ablation increases atrial fibrillation burden in patients with paroxysmal atrial fibrillation despite continuation of antiarrhythmic drug therapy

INTRODUCTION: Total atrioventricular nodal (TAVN) ablation and pacing is an accepted and safe treatment for patients with drug-refractory paroxysmal atrial fibrillation (AF). Many patients develop permanent AF within the first 6 months after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic drug therapy. We hypothesized that TAVN ablation itself creates an atrial substrate prone to AF. METHODS AND RESULTS: Patients participating in the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained on stable antiarrhythmic drug therapy throughout follow-up were included in this analysis. AF burden and the development of persistent AF in the preablation period were compared to two consecutive postablation periods. Echocardiographic changes also were evaluated. Twenty-two patients remained on stable drug therapy (9 men and 13 women, age 59 +/- 3 years). One patient developed persistent AF preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0 +/- 1.2 hours/day and increased to 10.4 +/- 2.2 hours/day and 11.8 +/- 2.3 hours/day in the two postablation follow-up periods (P < 0.05). In patients with fractional shortening (FS) >30% prior to ablation, FS decreased significantly from 39.4% +/- 1.3% to 36.4%+/- 1.7% (P < 0.05). In contrast, in patients with a FS < or =30% prior to ablation, FS increased from 27% +/- 0.8% to 33.6 +/- 1.7% (P < 0.05). CONCLUSION: TAVN ablation increases AF burden and facilitates the development of persistent AF in patients with paroxysmal AF despite the continuation of antiarrhythmic drugs. Loss of AV and/or interventricular synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch and increasing AF burden.     

Efficacy and safety of dabigatran in patients with atrial fibrillation scheduled for transoesophageal echocardiogram-guided direct electrical current cardioversion: a prospective propensity score-matched cohort study

Patients with atrial fibrillation (AF) are predisposed to a hypercoagulable state and are at an increased risk for thromboembolic events when undergoing procedures. This study investigated the long-term efficacy and safety of newly initiated anticoagulation with dabigatran versus uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). Consecutive adult patients with persistent AF scheduled to undergo DCC were included in the study. Patients received dabigatran 110 mg or 150 mg twice daily (bid) or VKA at therapeutic doses for at least 3?weeks before and 4?weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic and echocardiographic evaluation at each follow-up visit, and were followed up for a total period of 2 years. The primary efficacy outcome was the composite of stroke/transient ischaemic attack and systemic embolism. The primary safety outcome was major bleeding. 176 patients receiving dabigatran (77% dabigatran 150 mg bid) were propensity score-matched to 176 patients on VKA therapy. A low incidence of atrial thrombus (0.6%) at TEE was found in both groups (0.6%). The acute cardioversion success rate was 85.1% in the dabigatran group (149/175) and 83.4% in the VKA group (146/175). During the follow-up period, a similar low incidence of thromboembolic events (0.6%) was reported in both groups; the bleeding safety profile tended to favour dabigatran over VKA (1.1% vs 1.7%; P?=?0.3). Newly initiated anticoagulation with dabigatran in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy, during long-term follow up.     

Bleeding Rates in Veterans Affairs Patients with Atrial Fibrillation Who Switch from Warfarin to Dabigatran

Objectives

Clinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin.

Methods

We used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran).

Results

Compared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin.

Conclusions

Dabigatran may increase the likelihood of gastrointestinal bleeds.     

REVIEW: Atrial Fibrillation and Dabigatran: Has the Time Come To Use New Anticoagulants?

Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance found in clinical practice, increasing in prevalence with age. AF is often associated with structural heart disease, although a significant proportion has no detectable heart disease. In the last 2 decades, there has been an increase of 66% in hospitalizations for AF, and it is an extremely costly public health problem. AF is associated with an increased long‐term risk of stroke, heart failure, and all‐cause mortality. In fact, the mortality rate in patients with AF is about double that of patients in normal sinus rhythm. Antithrombotic therapy is recommended for all patients with AF to prevent thromboembolism, except those with lone AF or contraindications. Selection of the antithrombotic agent should be based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient. However, despite oral anticoagulation with vitamin K antagonists (warfarin or acenocoumarol) some patients still have thromboembolic events. Furthermore, for the majority of patients, international normalized ratio (INR) monitoring may be an inconvenience. This is why new anticoagulants, such as the direct thrombin inhibitors, are being investigated. The results of the RE‐LY trial have recently been published. In this study, in a population of patients with AF, dabigatran at 110 mg b.i.d was associated with stroke and systemic embolism rates similar to those associated with warfarin, and with lower rates of major hemorrhage. However, when dabigatran was administered at a dose of 150 mg, lower rates of stroke and systemic embolism and similar rates of major hemorrhage were found compared with warfarin. The aim of this review is to update information on the prevention of thromboembolic events in patients with AF and how dabigatran may change daily clinical practice.     

达比加群110 mg剂型在冷冻球囊消融术中应用的安全性和有效性

目的 探究达比加群110 mg剂型在心房颤动冷冻球囊消融术围术期与术后1年内应用的安全性和有效性。方法 选取自2018年1月～2019年6月在空军军医大学第一附属医院心脏内科接受冷冻球囊消融术治疗的阵发性或持续性房颤患者（n=148）,所有患者自入院时起均接受110 mg剂型达比加群抗凝治疗,门诊随诊1年并收集相关临床数据。描述与药物应用相关的血栓栓塞事件及出血事件,并使用多重Logistic回归分析寻找可能的影响因素。结果 患者围术期与随诊1年内均未发生临床栓塞事件与大出血事件。随诊1年的冷冻球囊消融术总成功率为77.70%。22例（14.9%）患者于手术后空白期（3个月）内发生轻度出血,此后所有患者均再未发现与药物应用相关的并发症。1例患者围手术期内发生急性心包填塞。多重Logistic回归分析显示高血压病史是应用110 mg剂型达比加群导致轻度出血的唯一危险因素（P<0.05）。结论 初步证明,110 mg剂型达比加群在心房颤动冷冻球囊消融术后1年内的抗凝管理中是安全有效的,未见症状性血栓栓塞事件以及药物相关大出血事件的发生;轻度出血是常见的药物不良反应,尤其对于既往有高血...     

Dabigatran Dual Therapy Versus Warfarin Triple Therapy Post–PCI in Patients With Atrial Fibrillation and Diabetes

ObjectivesThe aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BackgroundIt is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.MethodsIn RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.ResultsAmong patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.ConclusionsIn this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.     

Dabigatran for left ventricular thrombus

Male patient in dilated phase of hypertrophic cardiomyopathy had multiple hospitalizations during the past 2 years either due to congestive heart failure, stroke, scar epilepsy, or atrial fibrillation and ventricular tachycardia. Medication included evidence based therapy for heart failure, cordarone and warfarin. Anticoagulation had to be discontinued due to marked fluctuations in INR. Transthoracic Echocardiography (TTE) revealed a mobile mass in the left ventricle. He was treated with Dabigatran 110 mg twice a day for 4 months without any bleeding or embolic episode and complete resolution of thrombus.Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus.     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Stroke risk and suboptimal thromboprophylaxis in Chinese patients with atrial fibrillation: Would the novel oral anticoagulants have an impact?

Background

The risk of stroke associated with atrial fibrillation (AF) is higher in Far Eastern population than in Western population, and warfarin use suboptimal. There is uncertainty whether the novel oral anticoagulants (NOACs) would have a major impact on stroke prevention in Far Eastern populations with AF.

Objectives

We investigated current antithrombotic therapy use on stroke and bleeding risk, determinants of warfarin use and performed a modeling analysis of the net clinical benefit of the NOACs (apixaban, dabigatran) in a large cohort of Chinese patients with AF.

Methods

We studied 1034 Chinese patients (27.1% female, median age 75 years, interquartile range [IQR]: 63–83) with AF who were followed-up for an average of 1.9 years (IQR: 1.43–2.64). Stroke/thromboembolism (TE), and major bleeding associated to antithrombotic treatment were investigated. A modeling analysis was performed for the net clinical benefit balancing major bleeding against stroke/TE for dabigatran 110 mg bid, dabigatran 150 mg bid and apixaban, using their respective recent clinical trial outcome data.

Results

Using a Cox proportional hazard model, the Hazard Ratio [HR (95% confidence interval, CI)] for stroke/TE compared to no-antithrombotic therapy (no ATT) was 1.27 (0.65–2.50) on aspirin, 1.40 (0.35–3.57) on clopidogrel, 1.52 (0.72–3.23) on dual antiplatelets and 1.65 (0.76–3.57) on warfarin. The risk for major bleeding was 0.35 (0.14–0.85) on aspirin, 0.74 (0.24–2.29) on clopidogrel, 0.35 (0.11–1.10) on dual antiplatelets, and 0.88 (0.36–2.17) on warfarin. Binary logistic regression analysis showed persistent/permanent AF (Odds Ratio, OR, 2.03 [95%CI 1.05–3.92], p = 0.035) was associated with warfarin use, but age ≥ 75 years (0.26 [0.16–0.42], p < 0.001), aspirin (0.18 [0.12–0.27], p < 0.001) and clopidogrel (0.17 [0.08–0.33], p < 0.001) were independent determinants of non-use of warfarin.On modeling net clinical benefit (per 100 person-years [95% CI]), apixaban use compared to antiplatelet agents or no ATT was 3.29 (2.15–4.30) using Singer's method and 2.08 (1.18–3.21) with Connolly's method amongst high-risk patients. The use of dabigatran 110 mg bid and 150 mg bid compared to antiplatelet agents could reduce an additional 18.1 stroke/TE and 24.3 stroke/TE events, respectively. Compared to warfarin, dabigatran 150 mg bid had the best net clinical benefit.

Conclusions

There was suboptimal stroke prevention with no difference between antiplatelet and OAC treated patients, perhaps reflecting an inappropriate Target INR range. On modeling analyses, the use of the NOACs (apixaban and dabigatran) could provide better stroke prevention compared to antiplatelet (or warfarin) use in this Chinese AF population, with a positive net clinical benefit.