Warfarin In Atrial Fibrillation Patients Research Articles

Safety and efficacy of non-vitamin K antagonist oral anticoagulants compared to warfarin in patients with atrial fibrillation and end stage renal disease: a meta-analysis of randomized trials

Abstract Background Stroke prevention in patients with atrial fibrillation (AF) and end stage renal disease (ESRD) is difficult because of the lacking of high-quality evidence. Although there were few randomized trials comparing NOACs and warfarin in AF patients with ESRD, the small patient size prohibits these studies from making a conclusion. We aimed to perform a meta-analysis to evaluate currently available randomized trials in this special population. Methods We searched the literature for randomized clinical trials comparing NOAC to warfarin in AF patients with ESRD undergoing hemodialysis. Results A total of 3 randomized trials were identified from the literature (one for rivaroxaban [Valkyrie study] and two for apixaban [AXADIA-AFNET 8 and RENAL-AF]). About the principal efficacy outcome, NOACs did not decrease the risk compared to warfarin (relative risk [RR] 0.79, 95%CI 0.45-1.37) while a significant heterogeneity was noted (p = 0.03). In Valkyrie study, rivaroxaban had better efficacy outcome than warfarin (RR 0.57, 95%CI 0.43-0.75). For the safety outcome, the risk was similar between NOACs and warfarin (RR 0.81, 95%CI 0.52-1.27) without significant heterogeneity (p = 0.11)(Figure 1). The pooled event rate of 3 trials disclosed a high risk of all-cause mortality (39.9% for NOACs, 34.6% for warfarin) and cardiovascular mortality (10.1% for NOACs, 8.5% for warfarin) for AF patients with ESRD even on OACs (Figure 2). Conclusions This meta-analysis suggested that NOACs (rivaroxaban or apixaban) was at least as safe and effective as warfarin in AF patients with ESRD. Even on OACs, these patients remain at high risk of cardiovascular events and all-cause mortality. Integrated care and holistic management were important for this high-risk population.

Trends in use of Direct Oral Anticoagulants and Warfarin in Atrial Fibrillation Patients

Treatments used in atrial fibrillation therapy, such as those of anticoagulants, consist of vitamin K antagonists (warfarin) and direct oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban). The use of warfarin requires regular monitoring of prothrombin time (PT) and international normalised ratio (INR). The therapeutic dose range is narrow, but the price is cheaper. Oral anticoagulants are directed, the incidence of major bleeding is lower, ease of use, food and drug interactions are minor, the half-life is shorter, and there is a lack of laboratory monitoring needs. Based on this problem, researchers conducted a study to determine the trend of using warfarin and oral anticoagulants in patients with atrial fibrillation at a public hospital in Jakarta. This study uses a qualitative approach, with longitudinal methods and retrospective data using outpatient medical records for the period 2014 to 2018. The trend of using warfarin anticoagulants decreased from 82.3% in 2014 to 62% in 2016, while oral anticoagulants were reduced. Direct oral anticoagulants are rivaroxaban and dabigatran, which are more widely used than apixaban, and edoxaban; no data on their use has been obtained. The opposite was true from 2017 to 2018, when the use of warfarin increased and caused a decrease in the use of direct oral anticoagulants. This research is expected to contribute to various parties, both health practitioners and academics, in terms of selecting therapies for atrial fibrillation.

Real-world Experience in Managing Atrial Fibrillation in Patients with Renal Impairment; Rivaroxaban versus Warfarin.

The use of rivaroxaban in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) poses the risk of over- or underdosing. We aimed to compare rivaroxaban and warfarin in AF patients with moderate and severe renal impairment. This retrospective study was conducted between 2015 and 2016 to compare the use of warfarin (n = 164) and rivaroxaban (n = 149) in patients with AF and moderate or severe CKD. The study outcomes were survival, stroke, and major bleeding events. The median follow-up was 50 months (interquartile range: 23-60). Thirty-six patients had major bleeding: 24 with rivaroxaban and 12 with warfarin (P = 0.01). The rivaroxaban group had major bleeding in 3 patients with moderate CKD, 4 with severe CKD, and 17 on dialysis. Multivariable analysis of factors affecting major bleeding revealed that warfarin use lowered the risk of bleeding (hazard ratio: 0.34; P = 0.004). Stroke occurred in 14 patients: 6 in the rivaroxaban group and 8 in the warfarin group (P = 0.44). Survival at 1, 3, and 5 years was 89%, 77%, and 71% with warfarin and 99%, 94%, and 88% with rivaroxaban, respectively (P < 0.001). Multivariable analysis showed higher mortality in patients with lower creatinine clearance and those on warfarin. The safety of warfarin could be better than rivaroxaban in patients with CKD with fewer bleeding complications but similar stroke rates. Further studies on rivaroxaban dosing in patients on dialysis are required.

Rationale and Design of Rivaroxaban Estimation With Warfarin in Atrial Fibrillation Patients With Coronary Stent Implantation (REWRAPS).

Background: Recent major randomized trials revealed the superiority of non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) from 6 months to 2 years after percutaneous coronary intervention (PCI). However, whether NOAC monotherapy superiority over warfarin continues in real-world patients with a history of atrial fibrillation (AF), coronary stenting, and underlying chronic kidney disease (CKD) >1 year after PCI (e.g., at 5 years) has not been established. Methods and Results: In the Rivaroxaban Estimation with Warfarin in Atrial Fibrillation Patients with Coronary Stent Implantation (REWRAPS) study (NCT02024230), a multicenter, prospective, non-randomized, open-label, physician-initiated efficacy and safety study in Japan, 493 patients received either rivaroxaban or warfarin. The primary efficacy endpoint was major adverse cardiac and cerebrovascular events (MACCE), consisting of cardiac and stroke death, non-fatal myocardial infarction, non-fatal stroke, systemic embolism, and coronary revascularization. The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium 3 and 5). The primary composite endpoint was net adverse clinical events (NACE), defined as a combination of all-cause death and major bleeding. Conclusions: Completion of REWRAPS will provide, for the first time, evidence as to whether rivaroxaban is superior or non-inferior to warfarin with regard to the primary efficacy (MACCE), safety (major bleeding), or combined (all-cause death, major bleeding) endpoints in real-world patients with AF, coronary stenting, and underlying CKD an average of 5 years after PCI.

Impact of baseline renal function on the efficacy and safety of different Anticoagulants in Atrial Fibrillation Patients – A cohort study

BackgroundVitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear.MethodsThis study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment.ResultsThis study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) < 60 mL/min), 2846 patients with mild renal impairment (60 ≤ CrCl < 90 mL/min) and 1153 patients with CrCl ≥ 90 mL/min. Over the 3.3 ± 0.9 years follow-up period, the cumulative thromboembolic events rates and the cumulative event rates of major/fatal bleeding and ICH did not differ among the warfarin and different DOAC groups at different stages of chronic renal impairment. The annual incidences of thromboembolic events, major/fatal bleeding, GI bleeding, and ICH were similar among the warfarin and different DOAC groups at different stages of renal impairment.ConclusionThere did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

CO55 Efficacy and Safety of Direct Oral Anticoagulants (DOACS) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: A Systematic Review and Meta-Analysis

The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke.

Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis

BackgroundPatients with atrial fibrillation (AF) and frailty are a considerable group in clinical practice. However, existing studies provide insufficient evidence of anticoagulation strategies for these patients. Therefore, we conducted a meta-analysis to determine the effectiveness and safety outcomes of direct oral anticoagulants (DOACs) for these patients.MethodsRandomized controlled trials or observational studies reporting the data about the DOACs and warfarin therapy among frail AF patients were included. The search was performed in the PubMed and Embase databases up to March 2022. Frailty was defined using the most widely used claims-based frailty index or the cumulative deficit model-based frailty index.ResultsA total of 4 studies involving 835,520 patients were included. Compared with warfarin, DOACs therapy reduced the risks of stroke or systemic embolism (HR = 0.79, 95%CI: 0.69–0.90), ischemic stroke (HR = 0.79, 95%CI: 0.71–0.87), hemorrhagic stroke (HR = 0.52, 95%CI: 0.35–0.76), and all-cause death (HR = 0.90, 95%CI: 0.84–0.96). In safety outcomes, DOACs was significantly associated with reduced risks of major bleeding (HR = 0.79, 95%CI: 0.64–0.97) and intracranial hemorrhage (HR = 0.58, 95%CI: 0.52–0.65) compared to warfarin, but there were no statistically differences in gastrointestinal bleeding (HR = 0.97, 95%CI: 0.73–1.29).ConclusionsDOACs exerted superior effectiveness and safety outcome than warfarin in AF patients with frailty.

Effectiveness and safety of non-vitamin K direct oral anticoagulants in atrial fibrillation patients with bioprosthetic valve.

BackgroundNon-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown.MethodsWe retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death.ResultsThe mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56–2.34), major bleeding (HR 0.80, 95% CI 0.32–2.03) and all-cause death (HR 1.09, 95% CI 0.73–1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76–1.47). These outcomes were not different in various subgroups analyzed.ConclusionIn this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.

Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis.

The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke. Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims)as the randomization was broken. Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups. DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

Comparison of the Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants with Warfarin in Atrial Fibrillation Patients with a History of Bleeding: A Systematic Review and Meta-Analysis.

Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding. We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021. Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p=0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p<0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p=0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p<0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p<0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p<0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p=0.01). NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.

Efficacy and Safety of Apixaban vs. Warfarin in Atrial Fibrillation Patients: Systematical Review and Meta-Analysis

Background: Various treatment strategies to treat AF and reduce its complications have been developed, including anticoagulant administration. Non-Vitamin K antagonist oral anticoagulants (NOAC) are recommended by current guidelines. Different anticoagulants revealed different safety and efficacy characteristic. The real-world evidence-based recommendation is still needed to improve AF management. This study aimed to disclose apixaban safety and efficacy profile compared with warfarin in a real-world population. Methods: We collected data from articles around the world studies comparing Apixaban and Warfarin in NVAF patients recorded online from studies published around 2015 to 2020 that we were taking from a scientific database such as Embase ProQuest, PubMed, and Cochrane based on inclusion criteria. Data analysis was carried out using Review Manager Version 5.4.1 (Cochrane, Copenhagen, Denmark) using Mantel-Haenzel statistical method for categorical data to measure Relative Risk (RR) and 95% Confident Interval (CI). We use a random-effect analysis model if P for heterogeneity (pHet &lt;0.1) and a fixed-effect analysis model if pHet ≥0.1. Results: Apixaban show a benefit in preventing ischemic stroke (RR = 0.51; 95% CI=0.40-0.66; p = &lt;0.00001) ischemic stroke/systemic embolism (RR = 0.63; 95% CI=0.50-0.81; p = &lt;0.0002), and all-cause mortality (RR = 0.54; 95% CI=0.40-0.74; p = &lt;0.0001) relative to Warfarin. Apixaban also show benefit to prevent major bleeding (RR = 0.49; 95% CI=0.41-0.58; p = &lt;0.0001), GI bleeding (RR = 0.46; 95% CI=0.36-0.60; p = &lt;0.0001), and intracranial hemorrhage (RR = 0.45; 95% CI=0.36-0.57; p = &lt;0.0001) relative to Warfarin. Conclusions: Apixaban is over warfarin in efficacy and safety. Apixaban has a safer profile in reducing the risk of major bleeding, GI bleeding, and intracranial hemorrhage in AF patients.

Apixaban vs. Warfarin in Atrial Fibrillation Patients With Chronic Kidney Disease.

Background and Objectives: Real-world evidence of apixaban treatment in patients with chronic kidney disease remains scarce. This study aimed to compare the relative risk of stroke or systemic embolism (SE) and major bleeding between apixaban and warfarin in atrial fibrillation (AF) patients with different degrees of kidney function.Design, Setting, Participants, and Measurements: We evaluated newly diagnosed AF patients between 2004 and 2018, who were receiving apixaban or warfarin. Electronic medical record data were collected from a large healthcare delivery network in Taiwan. The outcomes of hospitalization for stroke/SE and major bleeding were compared with propensity-score matched apixaban and warfarin cohorts. Stratified analyses according to initial apixaban dose (standard dose of 10 mg/day vs. lower dose of 2.5–5.0 mg/day) and baseline estimated glomerular filtration rate were performed.Results: Each cohort involved 1,625 matched patients. Apixaban was significantly associated with a lower risk of stroke/SE (adjusted hazard ratio [aHR]: 0.74; 95% confidence interval [CI]:0.57–0.97; p = 0.03). The risk of major bleeding was not increased whether in standard doses (aHR: 0.66; 95% CI: 0.45–0.96; p = 0.03) or reduced doses (aHR, 0.84; 95% CI, 0.63–1.12; p = 0.23) of apixaban. Regarding kidney function, apixaban reduced the risk of stroke/SE by 37% in those with an eGFR of <30 ml/min/1.73 m2 (aHR: 0.63; 95% CI: 0.40–0.98; p = 0.04).Conclusions: Compared to warfarin, apixaban is associated with a reduced risk of stroke/SE and is consistent with a subset of AF patients with eGFR <30 ml/min/1.73 m2. Both standard and reduced doses of apixaban showed lower risk of major bleeding than those of warfarin.

Benefits and Harms of Low-Dose Rivaroxaban in Asian Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-World Studies

Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70–0.84, I 2: 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62–0.84, I 2: 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58–0.73, I 2: 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

Safety and efficacy of new oral anticoagulants compared to those of warfarin in AF patients with cancer: a meta-analysis of randomized clinical trials and observational studies.

Data on the efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer are limited. Therefore, we conducted a meta-analysis to compare the efficacy and safety between NOACs and warfarin in this population. A comprehensive search of the PubMed, Embase, and Cochrane databases for articles published through July 2020 was performed. An evaluation of each study was conducted, and data were extracted. Pooled odds ratio (OR) estimates and 95% CIs were calculated. Eight studies (3 randomized controlled trials (RCTs) and 5 retrospective cohort studies) involving a total of 24,665 patients were included. Among the RCTs, there were no significant differences in the rates of stroke or systemic embolism (OR=0.69; 95% CI, 0.45-1.06; P=0.09), venous thromboembolism (OR=0.91; 95% CI, 0.33-2.52; P=0.86), myocardial infarction (OR=0.74; 95% CI, 0.44-1.23; P=0.24), major bleeding (OR=0.81; 95% CI, 0.61-1.06; P=0.12), or major or nonmajor clinically relevant bleeding (OR= 0.98; 95% CI, 0.82-1.19; P=0.86) between the NOAC and warfarin groups. Among the observational studies, patients who used NOACs had a significantly lower risk than those who used warfarin. The prevalence rates of ischemic stroke (OR=0.51; 95% CI, 0.28-0.92; P=0.02), VTE (OR=0.50; 95% CI, 0.41-0.60; P<0.00001), major bleeding (OR=0.28; 95% CI, 0.14-0.55; P=0.0002), and intracranial or gastrointestinal bleeding (OR=0.59; 95% CI, 0.37-0.92; P=0.02) were significantly reduced in the NOAC group. Our meta-analysis confirms that NOACs are as safe and effective as warfarin and can be applied in the real world; this data can serve as a reference for clinical doctors for formulating treatment strategies.

Effect of Rivaroxaban or Apixaban in Atrial Fibrillation Patients with Stage 4-5 Chronic Kidney Disease or on Dialysis.

Anticoagulant treatment in non-valvular atrial fibrillation (AF) patients with severe chronic kidney disease (CKD) or on dialysis remains a matter of debate. The object of this study was to quantify the benefit-risk profiles of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. A comprehensive search of the Cochrane Library, PubMed, Ovid, and Google Scholar databases was performed for eligible studies that comparing the effect and safety of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were abstracted, and then pooled using a random-effects model. A total of seven studies, one post hoc analysis of RCT and six observational cohorts, were included in this meta-analysis. Compared with warfarin use, the use of rivaroxaban or apixaban was significantly associated with reduced risks of all-cause death (HR = 0.82, 95% CI 0.72-0.93) and gastrointestinal bleeding (HR = 0.87, 95% CI 0.80-0.95). There were no significant differences in the risks of stroke or systemic embolism (rivaroxaban, HR = 0.71, 95% CI 0.43-1.19; apixaban, HR = 0.86, 95%CI 0.68-1.09) and major bleeding (rivaroxaban, HR = 0.96, 95% CI 0.64-1.45; apixaban, HR = 0.56, 95%CI 0.28-1.12). Current evidence suggests that rivaroxaban or apixaban are safe and at least as effective as warfarin in patients with AF and stage 4-5 CKD or on dialysis.

Efficacy and safety of NOAC versus warfarin in AF patients with left atrial enlargement.

BackgroundLittle is known about the effects of anticoagulation in patients with atrial fibrillation (AF) and left atrial enlargement (LAE).MethodsData of patients with AF were retrieved from Chang Gung Research Database during 2007–2016. We excluded patients who were not using oral anticoagulants, used anticoagulants for <30 days, used ≥2 agents concomitantly or switched anticoagulants, had left atrial diameter missing from their data, were aged <65, had received valve surgeries, had mitral stenosis, or had a history of cancer. The primary outcomes were ischemic stroke (IS)/systemic embolism (SE), major bleeding, and death from any cause.ResultsWe identified 40,777 patients who received a diagnosis of AF. After the exclusion criteria were applied, 6,445 patients remained, 4,922 with LAE, and they were followed up for 2.4 ±1.9 years. The mean age of the patients was 77.32 ± 0.18 in the NOAC group and 76.58 ± 6.91 in the warfarin group (p < 0.0001); 48.24% of patients in the NOAC group and 46.98% of patients in the warfarin group were men (p > 0.05). The mean CHA2DS2-VASc score was 3.26 ± 1.05 in the NOAC group and 3.07 ± 1.12 in the warfarin group (p < 0.0001). The mean HAS-BLED score was 3.87 ± 3.81 in the NOAC group and 3.86 ± 3.80 in the warfarin group (p > 0.05). Furthermore, the mean LA diameter was 4.75 ± 0.63 cm in the warfarin group and 4.79 ± 0.69 cm in the warfarin group (p > 0.05). Among patients with LAE, NOAC was associated with significantly reduced IS/SE events (CRR = 0.63, 95% CI = 0.52–0.77), no difference in major bleeding (CRR = 0.91, 95% CI = 0.78–1.05), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52–0.80) compared with warfarin.ConclusionsIn elderly patients with AF and LAE, NOAC was associated with reduced IS/SE and death from any cause compared with warfarin, whereas no difference in major bleeding was observed between these treatments.

Safety and Efficacy of Apixaban, Rivaroxaban, and Warfarin in End-Stage Renal Disease With Atrial Fibrillation: A Systematic Review and Meta-Analysis

BackgroundThe use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited. MethodsElectronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model. ResultsA total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33–0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64–1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50–1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59–3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis. ConclusionsApixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.

Efficacy and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease: a Meta-Analysis and Systematic Review.

Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin.

Эффективность и безопасность прямых оральных антикоагулянтов и варфарина у больных фибрилляцией предсердий в составе многокомпонентной антитромботической терапии

Цель исследования. Сравнение эффективности и безопасности ПОАК и варфарина в составе многокомпонентной антитромботической терапии у больных ФП в условиях реальной клинической практики. Материалы и методы. Исследование представляет собой анализ пар больных, сопоставимых по риску инсульта, кровотечения и наличию сопутствующих заболеваний, получавших ПОАК или варфарин в составе МАТ и наблюдающихся в отделе клинических проблем атеротромбоза НМИЦ кардиологии в рамках регистра РЕГАТА 2. Влияние приема ПОАК и варфарина в составе МАТ на частоту комбинированной конечной точки эффективности (острый коронарный синдром, ишемический инсульт, венозные тромбоэмболические осложнения и сердечно-сосудистая смерть), а также конечной точки безопасности (геморрагические осложнения BARC 2–5) оценивали с помощью критерия Log-Rank. Отдельно проанализированы подгруппы больных в зависимости от уровня создаваемой антикоагуляции (принимавшие уменьшенную и полную дозы ПОАК и варфарин с уровнем TTR ≥ 65% и &lt; 65%). Результаты. Всего в исследование включена 81 пара пациентов (77,8% мужчины, средний возраст 67,2±7,6 лет). Медиана суммы баллов по шкале CHA2DS2-VASc составила 4, по шкале HAS-BLED – 3, медиана индекса Charlson – 6. В группе варфарина медиана TTR составила 67,0 %. Уменьшенную дозу ПОАК лечащие врачи назначили половине (50,6%) пациентов. Медиана длительности наблюдения составила 12 мес. ПОАК в полной дозе и варфарин с уровнем TTR ≥ 65 % в составе МАТ одинаково эффективны в отношении риска тромботических событий [OP 1.12, ДИ 0.34–3.71]. Назначение ПОАК в уменьшенной дозе ассоциируется с достоверным увеличением частоты всех тромботических событий по сравнению с пациентами, получавшими полную дозу ПОАК или варфарин с уровнем TTR≥65% (Log-Rank p=0,0378). В условиях ежемесячного контроля уровня антикоагуляции частота больших и клинически значимых кровотечений одинакова на фоне приема ПОАК и варфарина в составе МАТ (Log-Rank p=0,7286). Медиана длительности приема МАТ до первого большого или клинически значимого кровотечения составила 41 день. Заключение. Мерами, направленными на повышение безопасности и эффективности МАТ, является ограничение сроков комбинированного антитромботического лечения с назначением полной дозы ПОАК или варфарина с уровнем TTR≥65%.Aim of the study. To compare efficacy and safety of DOACs and warfarin as part of multicomponent antithrombotic therapy in AF patients in real clinical practice. Materials and methods. The study is an analysis of 81 pairs of patients comparable for CHA2DS2-VASc, HAS-BLED scores, and Charlson comorbidity index, of patients receiving DOACs or warfarin as part of multicomponent antithrombotic therapy who observed in the department of clinical problems of atherothrombosis of the NMIC cardiology under the REGATA Register 2. Influence of DOACs and warfarin as a part of MAT on the frequency of the composite efficacy endpoint (acute coronary syndrome, ischemic stroke, venous thromboembolic events and cardiovascular death) and safety endpoint (hemorrhagic complications BARC types 2–5) were assessed using the Log-Rank criterion. Also were analyzed subgroups of patients depending on anticoagulation level (patients received reduced and full doses of DOACs and warfarin with a TTR level of ≥ 65% and &lt;65%). Results. The study included 81 pairs of patients (77,8% men, mean aged 69 ± 8,2 years). The median total score CHA2DS2-VASc was 4, HAS-BLED score – 3, the median of the Charlson index composed – 6. In the warfarin group, the median TTR was 67%. Half (52%) of AF patients received reduced DOACs doses. Median follow up period was 12 month. Frequency of all thrombotic events for full DOACs doses and warfarin with a TTR level of ≥ 65 was similar [HR 1.12, CI 0.34–3.71] in AF patients requiring multicomponent antithrombotic therapy. Reduced DOACs doses are associated with significant increase in the frequency of all thrombotic events compared to patients who received full DOACs doses or warfarin with TTR level of ≥ 65 (Log-Rank p = 0.0378). In case of monthly monitoring of INR level frequency of major and clinically significant bleeding was similar for warfarin with regular monitoring of INR level and DOACs (Log-Rank p = 0.7286). Median duration of MAT before first BARC 2-3 type bleeding was 41 days. Сonclusions. The best option to improve the safety and efficacy of MAT is limiting the duration of combined antithrombotic treatment and prescribing a full dose of DOACs or warfarin with a TTR ≥ 65% level.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Peripheral Artery Disease: a Systematic Review and Meta-Analysis.

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with atrial fibrillation (AF) and peripheral artery disease (PAD) remain largely unknown. Therefore, we conducted a meta-analysis to explore the effects of NOACs versus warfarin in this population. We systematically searched the PubMed and Embase databases, with no linguistic restrictions, until December 2019 for relevant randomized controlled trials (RCTs) and observational studies. A random-effects model using an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). A total of six studies (three post hoc analyses of RCTs and three cohort studies) were included in this meta-analysis. Among AF patients treated with NOACs and warfarin, individuals with PAD had increased rates of all-cause death (RR = 1.26, 95% CI 1.07-1.48) and cardiovascular death (RR = 1.32, 95% CI 1.06-1.64) compared with those without PAD. In AF patients with PAD, we observed a similar risk of thromboembolic events, bleeding, and death with NOACs as with warfarin. In addition, there were no interactions between PAD and non-PAD subgroups regarding any of the reported outcomes of NOACs versus warfarin in AF patients (all Pinteraction > 0.05). Based on current evidence, AF patients with PAD are at a higher risk of death than those without PAD. Efficacy and safety outcomes with NOACs are comparable to those with warfarin, suggesting that the use of NOACs has effects similar to warfarin in AF patients with concomitant PAD.