Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.     

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.     

Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial

ObjectivesThe aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy 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.BackgroundPatients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.MethodsA total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y₁₂ inhibitor (and no aspirin), or warfarin plus a P2Y₁₂ inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.ResultsThere was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.ConclusionsIn RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.     

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.     

Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease

Background

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.

Comparative Stroke,Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation

BackgroundNonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness.MethodsWe performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC.ResultsCompared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban.ConclusionsAmong patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit–harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit–harm profile than rivaroxaban.     

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.     

Bleeding in patients with atrial fibrillation treated with dabigatran,rivaroxaban or warfarin: A retrospective population-based cohort study

BackgoundRandomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates.MethodsWe performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3 year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment.Results18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6–4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7–4.7) in dabigatran patients, and 4.1 (95% CI, 3.0–5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56–0.90) for warfarin, 0.4 (95% CI, 0.18–0.87) for dabigatran, and 0.27 (95%CI, 0.10–0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62–2.20) for warfarin, 2.98 (95% CI, 2.4–3.5) for dabigatran and 2.39 (95%CI, 1.6–3.5) for rivaroxaban.ConclusionsWe demonstrate similar bleeding rates with both dabigatran 150 mg and 110 mg and rivaroxaban compared to 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.     

National Trends in Ambulatory Oral Anticoagulant Use

Background

Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation.

Methods

We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014.

Results

Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%).

Conclusions

Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.     

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.     

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis

Introduction and objectives

To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation.

Does statin therapy decrease the risk for bleeding in patients who are receiving warfarin?

Purpose

Recent observations in patients with atrial fibrillation who are receiving warfarin suggest that concomitant treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) decreases the risk for bleeding.

Methods

We conducted a population-based, nested case-control study using the linked administrative databases of Ontario, Canada, to assess whether statin use decreases the risk of bleeding in warfarin users. Eligible patients were Ontario residents, age 66 years or more, with atrial fibrillation who were prescribed warfarin between April 1, 1994, and December 31, 2001. Patients were followed until hospitalization for upper gastrointestinal or intracranial bleeding, study end (March 31, 2002), discontinuation of warfarin, or death. Cases were matched to controls by age and sex. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between bleeding and statin use.

Results

We identified 79,207 warfarin users with atrial fibrillation. There were 1518 cases with an upper gastrointestinal or intracranial bleed and 15,100 matched controls without bleeding. Long-term (≥1 year) statin use was associated with a lower risk for any bleeding (OR = 0.80; 95% CI, 0.66-0.97). However, there was no association between bleeding and recent (<6 months) statin use (OR = 1.04; 95% CI, 0.74-1.48) or statin use of any duration (OR: 0.91; 95% CI, 0.77-1.07), suggesting potential confounding of the association between statin use and bleeding by a health-user effect.

Conclusion

Long-term statin use may be associated with a decreased risk for bleeding in warfarin users with atrial fibrillation. Additional research is needed to further explore this putative association.     

新型口服抗凝药治疗70岁以上老年心房颤动患者疗效及安全性的Meta分析

目的:系统评价新型口服抗凝药(NOACs)治疗70岁以上老年心房颤动(房颤)患者疗效及安全性。方法:计算机检索PubMed、Embase、Cochrane library等数据库,检索时间均从建库至2021年3月,收集其中收录的公开发表的关于NOACs(达比加群、利伐沙班、阿哌沙班、西美加群、艾多沙班)与华法林治疗70...     

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.     

Causes of Death and Influencing Factors in Patients with Atrial Fibrillation

Background

Atrial fibrillation is associated with a higher mortality, but causes of death of atrial fibrillation patients and their specific predictors have been less well defined. We aimed to identify the causes of death among atrial fibrillation patients and secondly, clinical predictors for the different modes of deaths.

Methods

Patients diagnosed with atrial fibrillation in a four-hospital institution between 2000 and 2010 were identified. During a follow-up of 929 ± 1082 days (median 456, interquartile 10-1584), 1253 deaths were recorded (yearly rate 5.5%).

Results

Cardiovascular deaths accounted for 54% and noncardiovascular for 43%. The three main causes of death were heart failure (29%), infection (18%), and cancer (12%). Fatal stroke or fatal bleeding each accounted for 7% of all deaths. On multivariate analysis, the strongest predictors of death were permanent atrial fibrillation, heart failure (whether with decreased or with preserved ejection fraction), previous bleeding, and renal failure, which were independently associated with an increase in the risk of all-cause mortality (35%, 78%, 42%, and 79%, respectively), cardiovascular mortality (43%, 129%, 46%, and 93%, respectively), and noncardiovascular mortality (21%, 45%, 40%, and 50%, respectively). Oral anticoagulant use was independently associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.62; 95% confidence interval [CI], 0.54-0.71; P <.0001), cardiovascular mortality (HR 0.60; 95% CI, 0.49-0.72; P <.0001), and noncardiovascular mortality (HR 0.60; 95% CI, 0.49-0.74; P <.0001).

Conclusions

The majority of deaths were related to a cardiovascular origin, and heart failure was the most common cause of death in atrial fibrillation patients. Despite the high risk of stroke associated with atrial fibrillation, only 7% died from stroke. Optimization of management of any underlying heart disease and associated comorbidities should be a relevant therapeutic target to reduce total mortality in atrial fibrillation patients.     

Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease

Background

To contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status.

Methods

Patients who initiated statin therapy between January 1, 2001 and December 31, 2009 were identified from a random sample of one million subjects in the Taiwan National Health Insurance Research Database. The outcome was atrial fibrillation/flutter. A proportional hazard regression model with time-varying statin use was applied to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) for atrial fibrillation/flutter according to current statin use versus treatment discontinuation, adjusted for baseline disease risk scores and time-varying covariates.

Results

A total of 6767 CKD and 63,678 non-CKD patients initiating statin therapy were included and followed for an average of 4.0 years. A total of 1118 participants experienced new-onset atrial fibrillation/flutter. The incidence of atrial fibrillation/flutter was approximately 2 fold higher in the CKD patients. Continuation of statin therapy was associated with a 22% (adjusted hazard ratio 0.78; 95% CI: 0.65–0.93) and 57% (adjusted HR 0.43; 95% CI: 0.27–0.68) decrease in atrial fibrillation/flutter hazard as compared with discontinuation in non-CKD and CKD patients, respectively.

Conclusions

Continuation of statin therapy was associated with a decreased risk of atrial fibrillation/flutter among CKD and non-CKD patients. However, further randomized studies are still needed to assess the association.     

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.