/pdf/2021-european-heart-rhythm-association-practical-guide-on-2pawim3hm9.pdf

2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation

Background and Purpose—The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. Methods—We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model. Results—Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52–0.83] versus 0.85 [0.77–0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44–0.74] versus 0.89 [0.76–1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19–0.52] versus 0.56 [0.44–0.70], P interaction=0.046) in par...

https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.115.009947

Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation Meta-Analysis

Background Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin. Objectives To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD. Search methods We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4). Data collection and analysis Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE. Main results Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin. Authors' conclusions Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

/pdf/direct-oral-anticoagulants-versus-warfarin-for-preventing-50xjlr872z.pdf

Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease

Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy.

Background and Purpose— Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA.

Methods— ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0–3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin.

Results— Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P <0.001; major bleeding 3.03% versus 2.64% per year; P <0.001; intracranial hemorrhage, 0.70% versus 0.40% per year; P <0.001). Among patients with previous IS/TIA, annualized intracranial hemorrhage rates were lower with HDER than with warfarin (0.62% versus 1.09%; absolute risk difference, 47 [8–85] per 10 000 patient-years; hazard ratio, 0.57; 95% confidence interval, 0.36–0.92; P =0.02). No treatment subgroup interactions were found for primary efficacy ( P =0.86) or for intracranial hemorrhage ( P =0.28).

Conclusions— Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA.

Clinical Trial Registration— URL: . Unique identifier: [NCT00781391][1].

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00781391&atom=%2Fstrokeaha%2F47%2F8%2F2075.atom

Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events: Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48).

Background and Purpose—The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate–high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously. Methods—We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose). The primary end point for this prespecified analysis of cerebrovascular events was all stroke (ischemic plus hemorrhagic), defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting ≥24 hours or fatal in <24 hours. Independent stroke neurologists unaware of treatment adjudicate...

https://www.ahajournals.org/doi/pdf/10.1161/strokeaha.114.006025?related-urls=yesl45%2F8%2F2372

Cerebrovascular Events in 21 105 Patients With Atrial Fibrillation Randomized to Edoxaban Versus Warfarin: Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48

Cheryl Lowe

Papers

Cerebrovascular Events in 21 105 Patients With Atrial Fibrillation Randomized to Edoxaban Versus Warfarin: Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48