Versus Vitamin K Antagonists Research Articles

Security profile of direct anticoagulants. Preferred use in atrial fibrillation

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in haemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKA), as well as the indications of specific antidotes and haemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high haemorrhagic risk.

Vitamin K antagonists vs. direct oral anticoagulants after transcatheter aortic valve implantation in atrial fibrillation.

To examine the risk of arterial thromboembolism, bleeding, and all-cause mortality in atrial fibrillation (AF) patients treated with direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) undergoing transcatheter aortic valve implantation (TAVI). In this nationwide observational cohort study, 735 patients undergoing TAVI from 1 January 2012 to 30 June 2017 with a history of AF and who were treated with oral anticoagulants were identified using data from Danish nationwide registries. Of these, 219 (29.8%) and 516 (70.2%) patients were treated with DOACs and VKAs, respectively. The DOAC group was characterized by a higher prevalence of previous arterial thromboembolism and a lower prevalence of chronic kidney disease compared with the VKA group. The distribution of age, sex, CHA2DS2-VASc and HAS-BLED scores, and concomitant antiplatelet therapy was similar between groups. Compared with VKA, treatment with DOACs was not associated with a significantly different 3-year absolute risk of arterial thromboembolism [9.6% (95% confidence interval, CI 4.7-16.5%) vs. 7.4% (95% CI 4.9-10.5%) in the DOAC and VKA group, respectively], bleeding [14.3% (95% CI 7.6-22.9%) vs. 13.3% (95% CI 9.9-17.1%)], or all-cause mortality [32.7% (95% CI 21.8-44.0%) vs. 32.0% (95% CI 26.8-37.3%)]. In adjusted analyses, treatment with DOACs, when compared with VKAs, was not associated with a significantly different rate of arterial thromboembolism [hazard ratio (HR) 1.23 (95% CI 0.58-2.59)], bleeding [HR 1.14 (95% CI 0.63-2.06)], or all-cause mortality [HR 0.93 (95% CI 0.61-1.40)]. In patients with AF undergoing TAVI, treatment with DOACs was not associated with a significantly different risk of arterial thromboembolism, bleeding, or all-cause mortality compared with VKA.

6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants

Abstract Background Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Purpose To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs). Methods We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs. Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96 Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonist (VKA) among patients with atrial fibrillation and hypertrophic cardiomyopathy: a systematic review and meta-analysis

Background/objectives: Long-term oral anticoagulant therapy is recommended for patients with hypertrophic cardiomyopathy (HCM) who develop atrial fibrillation (AF) to prevent cardioembolic complications. In patients with non-valvular AF, direct oral anticoagulants (DOACs) has been proved to be non-inferior to adjusted-dose vitamin K antagonist (VKA). However, the role of DOACs in patients with AF in the setting of HCM has not been fully established.Methods: A comprehensive literature review was conducted by searching for published articles indexed in MEDLINE and EMBASE databases from inception through 1 May 2019. Eligible studies must start with recruitment of patients with AF in the setting of HCM who received either DOACs or VKA. The studies must follow them for the occurrence of ischaemic stroke. Hazard ratio (HR) and confidence interval (CI) of developing ischaemic stroke between the two groups must be reported. Pooled HR was calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.Results: A total of three retrospective cohort studies with 4,418 participants met the eligibility criteria and were included into the meta-analysis. A significantly lower risk of all-cause death was observed in the DOACs group than in the VKA group with the pooled HR of 0.43 (95% CI, 0.33–0.58, I2 = 0%). However, the risk of ischaemic stroke among patients with AF and HCM who received DOACs was not significantly different from those who received VKA with the pooled HR of 0.95 (95% CI, 0.73–1.22, I2 = 0%). Both major bleeding and intracranial bleeding were also not significantly different between those who received DOACs versus those who received VKA with the pooled HR of 0.94 (95% CI, 0.70–1.26, I2 = 0%) and 0.61 (95% CI, 0.27–1.37, I2 = 0%), respectively.Conclusions: The current study found that the risk of all-cause death was significantly reduced but the risk of ischaemic stroke, major bleeding and intracranial bleeding were not significantly different between patients with AF and HCM who had received DOACs and those who received VKA.

Perfil de seguridad de los anticoagulantes directos. Uso preferente en fibrilación auricular

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitaminK antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk.

Shorter Hospital Stay and Fewer Hospitalizations in Patients With Visible Hematuria on Direct Oral Anticoagulants Compared to on Vitamin K Antagonists

ObjectiveTo investigate the influence of type of anticoagulation – direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) – on length of hospital stay (LOS) and hospitalization rates in patients with visible hematuria, as visible hematuria in anticoagulated patients can be distressing, difficult to control and even life-threatening. MethodsThis retrospective cohort study was conducted at the emergency department (ED) of a tertiary university hospital in Switzerland. All patients admitted with visible hematuria from January 1, 2013 to December 31, 2016 were included. We compared the primary clinical outcome parameters (hospitalization rate and LOS) as well as secondary outcomes (ICU admission, ED LOS, and in-hospital mortality) in patients with visible hematuria on either DOAC therapy, VKA therapy or no anticoagulants. ResultsWe included 811 (100%) patients with visible hematuria; 53 (6.5%) patients were on DOAC, compared to 85 (10.5%) on VKA and 673 (83.0%) patients without any anticoagulation. In confounder-adjusted multivariable testing, there were fewer hospitalizations (odds ratio: 2.2, 95% confidence interval [CI]: 1.1-4.9, P = .028) and shorter LOS (geometric mean ratio: 2.2, 95% CI: 1.3-4.0, P = .006) on DOAC than on VKA. The secondary outcomes were not significantly associated with the anticoagulation groups. No differences were found between the DOAC and no-anticoagulant groups for any outcome. ConclusionVisible hematuria in patients on DOAC therapy is associated with shorter hospital stays and fewer hospitalizations compared to VKA.

Real-life Performance of Edoxaban in Elderly Patients With Atrial Fibrillation: a Multicenter Propensity Score–Matched Cohort Study

PurposeThe purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting. MethodsA propensity score–matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack, and systemic embolism. FindingsA total of 130 patients receiving edoxaban 60 mg (EDO) treatment were compared with the same number of VKA recipients. The mean follow-up was 16 (2.6) months. The cumulative incidence of thromboembolic events in the EDO and VKA groups was 1.5% (2 of 130) and 2.3% (3 of 130), respectively (P < 0.6). The cumulative incidence of major bleeding events was 1.5% (2 of 130) in the EDO group and 3.1% (4 of 130) in the VKA group (P < 0.4). The total anticoagulant therapy discontinuation rate was 2.3% (3 of 130) in the EDO group and 4.6% (6 of 130) in the VKA group (P < 0.3). A nonsignificant trend in improved adherence was observed between the EDO and VKA groups (81% vs 78%; P = 0.6). ImplicationsEdoxaban therapy showed a good real-life performance among elderly patients (aged ≥75 years) with AF.

Quality of life, adherence and satisfaction of patients with auricular fibrillation treated with dabigatran or vitamin K antagonists

ObjectiveTo analyze the quality of life, adherence and satisfaction of patients with nonvalvular auricular fibrillation (NVAF) treated with dabigatran versus vitamin K antagonists (VKA) in cardiology consultations in Spain. MethodsWe conducted an observational, comparative, prospective and multicentre study of patients with NVAF treated in cardiology departments, who started treatment with dabigatran or VKA in the month prior to the baseline visit. The follow-up lasted 6 months. We analyzed quality of life (using the validated AF-QoL 18 questionnaire [0, minimum; 100, maximum]), adherence (using the Morisky-Green test) and the cardiologist's perception (using a specific questionnaire [0, completely dissatisfied; 10, completely satisfied]). ResultsWe analyzed 1015 patients (mean age, 73.3±9.4 years; 57% men; CHA2DS2VASc, 3.4±1.5; HAS-BLED, 1.5±1.0) who were treated with dabigatran (74.7%) or with VKA (25.3%). The total quality-of-life scores remained constant throughout the follow-up (47.9±23.5 and 48.6±24.4 at baseline and at 6 months, respectively; p=NS) but were higher at 6 months for the dabigatran group (50.6±24.7 vs. 42.8±22.5; p<.001). Treatment adherence was high during the study but greater with dabigatran at 6 months (89.2% vs. 81.1%; p=.001). There was a better perception of the cardiologist regarding the satisfaction of the patients treated with dabigatran at 6 months (9.0±1.2 vs. 6.6±2.2; p<.001). ConclusionsFor patients with NVAF and high thromboembolic risk treated in cardiology consultations, the adherence, satisfaction and quality of life were higher for the patients treated with dabigatran than for those treated with VKA.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients Undergoing Cardioversion for Atrial Fibrillation: a Systematic Review and Meta-analysis.

Clinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation (AF). We performed a systematic review and meta-analysis to compare the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with AF undergoing cardioversion. We searched CENTRAL, MEDLINE, and EMBASE for randomized controlled trials (RCTs) and observational studies comparing DOACs to VKAs in patients undergoing cardioversion for AF. We performed title, abstract, and full-text screening, data extraction, and risk of bias evaluation independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. We identified three eligible RCTs (n = 5203) and 21 observational studies (n = 11,855). The three RCTs and four observational studies were at low risk of bias. In RCTs (mean follow-up, 30days), thromboembolic events occurred in 0.18% of patients receiving DOACs, as compared with 0.55% receiving VKAs (relative risk [RR] 0.40, 95% CI [0.13, 1.24], moderate quality). Major bleeding occurred in 0.42% of patients receiving DOACs as compared with 0.64% receiving VKAs (RR 0.62, 95% CI [0.28, 1.35], moderate quality), and death occurred in 0.28% of patients receiving DOACs as compared with 0.38% receiving VKAs (RR 0.70, 95% CI [0.23, 2.10], low quality). Confidence in the estimates of effect for observational studies was very low. DOACs peri-cardioversion in patients with AF appears safe from both a bleeding and thromboembolic risk perspective. Available evidence supports the use of DOACs as standard of care peri-cardioversion in patients with AF.

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AimsEdoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested.Methods and resultsThe ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02–1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62).ConclusionUninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.

Anticoagulantes orales directos frente a antagonistas de la vitamina K en pacientes del «mundo real» con fibrilación auricular no valvular. Estudio FANTASIIA

Introduction and objectivesTo compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. MethodsThe FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. ResultsA total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke—0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032—, severe bleedings—2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044—, cardiovascular death—1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009—, and all-cause death—3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016—. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. ConclusionsCompared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.Full English text available from: www.revespcardiol.org/en

Calidad de vida, adherencia y satisfacción en pacientes con fibrilación auricular tratados con dabigatrán o antagonistas de la vitamina K

ObjectiveTo analyse the quality of life, adherence and satisfaction of patients with nonvalvular auricular fibrillation (NVAF) treated with dabigatran versus vitamin K antagonists (VKA) in cardiology consultations in Spain. MethodsWe conducted an observational, comparative, prospective and multicentre study of patients with NVAF treated in cardiology departments, who started treatment with dabigatran or VKA in the month prior to the baseline visit. The follow-up lasted 6 months. We analysed quality of life (using the validated AF-QoL 18 questionnaire [0, minimum; 100, maximum]), adherence (using the Morisky-Green test) and the cardiologist's perception (using a specific questionnaire [0, completely dissatisfied; 10, completely satisfied]). ResultsWe analysed 1015 patients (mean age, 73.3±9.4 years; 57% men; CHA2DS2VASc, 3.4±1.5; HAS-BLED, 1.5±1.0) who were treated with dabigatran (74.7%) or with VKA (25.3%). The total quality-of-life scores remained constant throughout the follow-up (47.9±23.5 and 48.6±24.4 at baseline and at 6 months, respectively; P=NS) but were higher at 6 months for the dabigatran group (50.6±24.7 vs. 42.8±22.5; P<.001). Treatment adherence was high during the study but greater with dabigatran at 6 months (89.2% vs. 81.1%; P=.001). There was a better perception of the cardiologist regarding the satisfaction of the patients treated with dabigatran at 6 months (9.0±1.2 vs. 6.6±2.2; P<.001). ConclusionsFor patients with NVAF and high thromboembolic risk treated in cardiology consultations, the adherence, satisfaction and quality of life were higher for the patients treated with dabigatran than for those treated with VKA.

Meta-Analysis of Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Patients with Active Malignancy

IntroductionVenous thromboembolism (VTE), is the second leading cause of death in patients with cancer. The risk of VTE in patients with cancer is 4 to 7-fold, when compared to the general population. Even during anticoagulant treatment, the cumulative incidence of recurrent VTE is 3.5 times higher in patients with cancer than in cancer-free patients. Low-molecular-weight heparin has been the “gold standard” for the of treatment for VTE in cancer associated thrombosis, following the landmark trial by Lee et al.MethodsWe conducted a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants in patients with cancer. We systematically searched Medline for randomized-control clinical trials and post-hoc analyses. For each study, data on recurrent VTE, major or clinically relevant non-major bleeding (CRNMB), and major bleeding (MB) were extracted. We included randomized control trials (RCT's) where interventions consisted of direct oral anticoagulants (DOA) versus vitamin K antagonists (VKA) or low molecular weight heparins (LMWH), in which all or a part of the study population had active cancer. We excluded studies that were not comparing DOA versus VKA/LMWH or did not have a subset of active cancer patients.ResultsSeven studies met our eligibility criteria. Data for recurrent VTE was extractable from all 7 RCT's. There were 2178 enrolled participants total.The pooled results show evidence for a lower incidence of recurrent VTE with the use of DOA versus VKA/LMWH. The pooled risk ratio for recurrent VTE was 0.68 (95% confidence interval 0.50 to 0.93; P = 0.01). There was negligible heterogeneity among the trials (I2 = 0%; P = 0.99).Data for major bleeds was extractable from 6 RCT's, including 1952 enrolled participants total. The pooled results show no evidence for a difference in frequency of major bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 1 (95% CI 0.53 to 1.87; P= 0.99). There was moderate heterogeneity among trials (I2 = 40%; P = 0.17)Data for clinically relevant bleeding was extractable from 6 RCT's, including 1952 enrolled participants total. The pooled results show no evidence for a difference in frequency of nonmajor but clinically relevant bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 1.06 (95% CI 0.80 to 1.42; P= 0.68). There was negligible heterogeneity among trials (I2 = 27%; P = 0.24).Data for all bleeds (major or nonmajor) was extractable from all 7 RCT's. There were 2178 enrolled participants total. The pooled results show no evidence for a difference in frequency of bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 0.95 (95% CI 0.68 to 1.32; P= 0.74). There was substantial heterogeneity among trials (I2 = 65%; P = 0.02).ConclusionsOur results suggest that DOACs might reduce the incidence of VTE recurrence in patients with cancer without putting them at high risk for major bleeds or clinically relevant nonmajor bleeds. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PCV79 - REAL-WORLD COST-EFFECTIVENESS OF RIVAROXABAN COMPARED WITH VITAMIN K ANTAGONISTS IN THE CONTEXT OF STROKE PREVENTION IN ATRIAL FIBRILLATION IN FRANCE

To evaluate the cost-effectiveness of rivaroxaban vs. vitamin K antagonists (VKAs) such as warfarin, for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) in France, using real-world (RW) evidence, from a national health insurance perspective. A Markov model considering a 30-year time span with cycle lengths set to 3 months was developed. Patient data for characteristics of the model population were obtained from a RWE study, considered as a relevant source of characteristics for French patients with NVAF. The model used RW baseline clinical event data drawn from different sources to inform expected event and persistence rates for VKA and rivaroxaban treatment arms. A meta-analysis of RW studies provided treatment effect data for rivaroxaban compared to VKA. Model outcomes included: costs (drug costs, clinical event costs, and VKA monitoring costs), quality adjusted life-years (QALY); life-years (LY) gained; incremental cost per QALY; incremental cost per LY; number of stroke events; number of gastro-intestinal bleeds; and number of myocardial infarctions. Sensitivity analyses were run to better understand the results drivers and robustness. In the base-case analysis, the incremental total cost was €826 and total incremental QALYs and LYs were 0.103 and 0.114, respectively. The resulting incremental cost/QALY and incremental cost/LY were €8,015 and €7,246, respectively. The results were most sensible to inclusion of treatment-specific disutility, and RW baseline clinical event data. Although there is no official cost-effectiveness threshold in France, this study demonstrates that rivaroxaban can be considered cost-effective vs VKA in a real-world setting, using a French national insurance perspective.

An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial fibrillation catheter ablation

Catheter ablation is recommended as a first- or second-line rhythm control therapy for selected patients with atrial fibrillation (AF). There is a wide variability in the periprocedural management of oral anticoagulation in patients undergoing AF ablation. We aimed to perform an updated meta-analysis of novel oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) as uninterrupted anticoagulation in patients undergoing AF ablation. Databases and conference abstracts were searched. Studies were excluded if oral anticoagulants were held at any periprocedural period. The primary outcomes were stroke or transient ischemic attack (TIA) and major bleeding. Twelve studies and 4962 patients were included. Stroke or TIA was rare (NOAC, 0.08%; VKA, 0.16%) and not different between groups (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.19-2.30). The incidence of silent cerebral embolic events was also not significantly different between NOACs (8%) and VKAs (9.6%) (OR 0.86; 95% CI 0.42-1.76). Major bleeding was significantly reduced in the NOAC group (0.9%) as compared with VKA-treated patients (2%) (OR 0.50; 95% CI 0.30-0.84; P < .01). This finding was confirmed in a subgroup analysis of randomized and cohort studies with matched controls (OR 0.45; 95% CI 0.24-0.83; P = .01). There was no significant difference in the outcomes of individual NOACs and VKAs, although these analyses may have been underpowered to detect minor differences in such rare outcomes. In patients undergoing AF ablation, uninterrupted periprocedural NOACs are associated with a low incidence of stroke or TIA and a significant reduction in major bleeding as compared with uninterrupted VKAs.

Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study

Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p < 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p < 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.

Initiation of anticoagulation in atrial fibrillation: which factors are associated with choice of anticoagulant?

The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Using Danish nationwide registry data, we identified AF patients initiating either a VKA or a NOAC from 22 August 2011 until 30 September 2016. We compared patient characteristics including age, gender, comorbidities, concomitant pharmacotherapy and CHA2 DS2 -VASc and HAS-BLED scores in patients initiated on a VKA, dabigatran, rivaroxaban or apixaban. Differences were examined using multivariable logistic regression models. The study population comprised 51981 AF patients of whom 19989 (38.5%) were initiated on a VKA, 13242 (25.5%) on dabigatran, 8475 (16.3%) on rivaroxaban and 10275 (19.8%) on apixaban. Those patients initiated on apixaban had higher mean±SD CHA2 DS2 -VASc scores than those initiated on a VKA (3.1±1.6 vs. 2.9±1.6). Those initiated on dabigatran had lower mean CHA2 DS2 -VASc scores (2.7±1.6) than all other groups. Patients with a history of a prior stroke were significantly more likely to be initiated on a NOAC compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28-1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67-0.77). Atrial fibrillation patients who were initiated on apixaban had higher stroke risk scores than patients initiated on VKAs. Interestingly, opposite results were found for dabigatran.

Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry.

AimsIn patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time.MethodsFrom September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry.ResultsA total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001).ConclusionAccording to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that NOAC use is increasing and there is a significant decrease in VKA use.

EFFECTIVENESS AND SAFETY OF DIRECT ORAL ANTICOAGULANTS COMPARED WITH VITAMIN-K ANTAGONISTS: INITIAL RESULTS FROM A COHORT STUDY IN THE NATIONWIDE FRENCH CLAIMS AND HOSPITALIZATION DATABASE (SNIIRAM)

Background: The real-life benefits and risks of the direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) have been disputed. This study aimed to compare the 1-year risk of major events for new users of dabigatran (D) or rivaroxaban (R) vs. vitamin K antagonists (VKA) in NVAF

Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials

Background and objectivesThe relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2–3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial. MethodsIn this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4<INR<3.5) for the prevention of arterial thrombosis with a minimum of three month follow-up and of 50 patients per treatment arm. The outcome measures were major bleedings and intracranial bleedings. ResultsTen eligible trials including 9047 patients were included, 451 of whom experienced major bleedings and 62 had intracranial bleeding. The 10 studies were homogeneous in spite of different clinical settings, including atrial fibrillation, heart failure and cerebral ischemia from arterial origin. Mean achieved INR on VKA varied from to 2.1 to 2.6. Compared with VKA, aspirin had an overall lower major bleeding risk (relative risk=0.58; 95% CI: 0.46–0.75; p<0.001). There was a non-significant trend for a lower intracranial bleeding risk on aspirin versus VKA (relative risk=0.65; 95% CI: 0.40–1.06; p=0.09). ConclusionMajor bleeding risk is substantially lower on aspirin than on VKA targeting current usual INR range. Physicians should take into account this data when choosing between different antithrombotic regimens.