Factor XI inhibitors versus direct oral anticoagulants for stroke prevention in atrial fibrillation: a systematic review of efficacy and safety

Direct Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves

Advances in Neurocardiology: Focus on Atrial Fibrillation.

Background: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD. Summary: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30–50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin. Key Messages: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.

Direct Oral Anticoagulants in Patients with Cirrhosis Appear Safe and Effective

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Left Atrial Appendage Closure vs Direct Oral Anticoagulants in Atrial Fibrillation: Meta-Analysis of Randomized Trials.

Scientific and Standardization Committee Communication: Guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: Recommendations for standardized reporting of procedural/surgical bleed risk and patient‐specific thromboembolic risk

Patient characteristics and real-world outcomes among atrial fibrillation patients treated with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in Spain

Unlike in non-surgical settings, many centres continue to favour vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) following major cardiac surgery. Current guidelines indicate insufficient data on the use of direct oral anticoagulants (DOACs) early after cardiac surgery. This study aims to evaluate whether DOACs are non-inferior to VKAs in terms of efficacy and safety for stroke prevention in post-operative AF. MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov were searched from inception till 2 July 2024, and relevant reviews were screened as grey literature. Studies comparing DOACs with VKAs for stroke prevention in patients with (post-operative) AF after major cardiac surgery were included. Studies on patients with mechanical valve replacement or moderate to severe mitral stenosis were excluded. Outcomes of interest included thromboembolic events, major bleeding and mortality up to 6 months after cardiac surgery. Eleven studies, including two randomized controlled trials, reporting on >18,000 patients were analyzed. There were no significant differences between DOACs and VKAs in thromboembolic events (OR: 0.96; CI: 0.62-1.50; I2: 0%), any stroke (OR: 1.44; CI: 0.61-3.41; I2: 0%), major bleeding (OR: 0.97; CI: 0.60-1.56; I2: 48%), all-cause mortality (OR: 1.00; CI: 0.73-1.37; I2: 0%) or admission duration (MD: -0.33; CI: -1.16-0.49; I2: 0%) in the first 6 months after cardiac surgery. There is no high-quality evidence that DOACs and VKAs differ in efficacy or safety for stroke prevention in AF after cardiac surgery. While awaiting high-quality randomized data, our meta-analysis found no evidence to support routinely avoiding DOACs or favouring VKAs in this setting. Review registration number: CRD42023412592.

The New Canadian Cardiovascular Society Algorithm for Antithrombotic Therapy of Atrial Fibrillation Is Appropriately Based on Current Epidemiologic Data

In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation has been slow and varied across different Clinical Commissioning Groups (CCGs). This study aimed to profile the prescribing of oral anticoagulants for stroke prevention in patients with atrial fibrillation over 3years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student's t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. The early uptake of DOACs significantly increased over the study period (p < 0.0001; medium size effect φc = 0.372). There was no statistically significant difference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N = 257) and driving the use of DOACs (72%, N = 71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin thana DOAC. The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial

Bioprosthetic Valve Thrombosis while on a Novel Oral Anticoagulant for Atrial Fibrillation

ObjectivesThis study aimed to estimate the budget impact of adopting direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation in Malawi after the inclusion of DOACs in the World Health Organization’s essential medicine list. MethodsA model was developed in Microsoft Excel. An eligible population of 201 491 was adjusted with 0.05 % incidence rate and mortality rates yearly according to the treatments. The model estimated the implication of supplementing rivaroxaban or apixaban to the standard treatment mix (also the comparator), thus warfarin and aspirin. The current market share of 43% aspirin and 57% warfarin was adjusted proportionally with 10% DOAC uptake in the first year and 5% annually over the subsequent 4 years. Clinical events of stroke and major bleeding from the ROCKET-AF and ARISTOTLE trials were used because health outcome indicators affect resource utilization. The analysis was conducted solely from the Malawi Ministry of Health perspective and it considered direct costs over 5 years. The sensitivity analysis involved varying drug costs, population, and care costs from both public and private sectors. ResultsThe research suggests that despite potential savings of $6 644 141 to $6 930 812 in stroke care because of fewer stroke events, the total Ministry of Health healthcare budget (approximately $260 400 000) may increase by between $42 488 342 to $101 633 644 in 5 years because drug acquisition costs are greater than savings. ConclusionsWith a fixed budget and current DOACs prices, Malawi can consider using DOACs in patients at the highest risk while waiting for cheaper generic versions.

Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up. This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment. Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing. Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education.