Safety Of Non-vitamin K Antagonist Oral Anticoagulants Research Articles

Comparative safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation: A network meta-analysis

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulant in the treatment of patients with morbid obesity or high body weight with venous thromboembolism: A meta-analysis.

Venous thromboembolism (VTE) poses a significant health risk to patients with morbid obesity or high body weight. Non-vitamin K antagonist oral anticoagulants (NOACs) are emerging treatments, but their effectiveness and safety compared with vitamin K antagonists (VKAs) in this population are yet to be thoroughly studied. We conducted a systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four electronic databases were searched for relevant studies comparing the efficacy and safety of NOACs and VKAs in treating patients with VTE with a body mass index > 40 kg/m2 or body weight > 120 kg. Eligible studies were scored for quality using the Newcastle-Ottawa Scale. Thirteen studies were included. The meta-analysis results showed that compared to VKAs, NOACs significantly decreased the risk of VTE occurrence (odds ratio = 0.72, 95% CI: 0.57-0.91, I2 = 0%, P < .001) and were associated with a lower risk of bleeding (odds ratio = 0.74, 95% CI: 0.58-0.95, I2 = 0%, P < .05). Subgroup analysis showed that in the cancer patient subgroup, both risks of VTE occurrence and bleeding were lower in the NOAC group than in the VKA group. In patients without cancer, the risk of VTE was significantly lower in the NOAC group. NOACs appear to be more effective and safer than VKAs in patients with morbid obesity or a high body weight with VTE. However, further large-scale randomized controlled trials are required to confirm these findings.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients with β-Thalassemia.

Background. Patients with β-thalassemia have a high incidence of atrial fibrillation (AF) and other supraventricular arrhythmias. The use of non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prophylaxis in patients with β-thalassemia has not been systematically evaluated. Methods. We enrolled patients with transfusion-dependent β-thalassemia, who were on treatment with NOACs for thromboembolic prophylaxis of supraventricular arrhythmias. Data on thromboembolic and bleeding events were collected. Results. Eighteen patients were enrolled. The patients had a history of AF (sixteen), typical atrial flutter (five), and atypical atrial flutter (four). The patients were treated with dabigatran (seven), apixaban (five), rivaroxaban (four) or edoxaban (two). The mean follow-up duration was 22 ± 15 months. No thromboembolic events were reported. No major bleedings were observed. Three patients had non-major bleeding events. Two patients reported dyspepsia during treatment with dabigatran and were shifted to a different NOAC. Conclusions. Our study suggests the efficacy and safety of NOACs in patients affected by transfusion-dependent β-thalassemia.

Cardiovascular and renal protective effects of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation.

AimData on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF.Methods and resultsPatients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69–0.89] p<0.001), CKD stage 4 (HR, 0.5 [95% CI, 0.28–0.89], p = 0.02), and ESRD (HR, 0.15[95% CI, 0.08–0.32], p<0.001) than warfarin use. NOACs and warfarin did not significantly differ with respect to stroke reduction (HR, 1.05 [95% CI, 0.88–1.25], p = 0.19). NOAC use was associated with a lower risk of intracranial hemorrhage (HR, 0.6 [95% CI, 0.44–0.83], p = 0.0019), CV death (HR, 0.55 [95% CI, 0.43–0.70], p<0.001), and all-cause death (HR, 0.6 [95% CI, 0.52–0.69], p<0.001) than warfarin use.ConclusionNOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

A Meta-Analysis Comparing Different Oral Anticoagulation for the Treatment of Ventricular Thrombus

Background: Patients with ventricular thrombus (VT) require anticoagulation therapy and it remains unknown that whether non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are more effective. Objective: We aimed to compare the effectiveness and safety of NOACs with VKAs on the rate of thrombus resolution and clinical outcomes. Methods: MEDLINE, PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database and Wanfang Database, were searched up to November 22, 2021. The primary outcome was the rate of thrombus resolution, and the secondary outcomes were bleeding, stroke or systemic embolism (SSE), stroke and all-cause death. Odds ratio (OR) and 95% confidential intervals (CI) were used for the pooled results. Results: Eighteen studies with 1755 participants (NOACs, n = 607; VKAs, n = 1148) were included. There were no significant differences in thrombus resolution (OR 0.92, 95% CI 0.68–1.23, p = 0.558), bleeding (OR 0.85, 95% CI 0.54–1.35, p = 0.496), SSE (OR 0.77, 95% CI 0.41–1.43, p = 0.401), stroke (OR 0.65, 95% CI 0.29–1.49, p = 0.312) or all-cause death (OR 1.02, 95% CI 0.63–1.67, p = 0.925) between NOACs and VKAs. Subgroup analyses showed a statistics difference in thrombus resolution between NOACs and VKAs among studies which enrolled patients with or without dabigatran (Yes: OR 0.80, 95% CI 0.59–1.08; No: OR 1.48, 95% CI 1.00–2.19; p = 0.01), while no significances were observed according to baseline characteristics. Conclusions: Our findings showed that NOACs were comparable to VKAs in thrombus resolution as well as clinical outcomes. In studies that enrolled patients without dabigatran, the thrombus resolution seemed to be greater in NOACs group than VKAs group. And in different proportion of baseline left ventricular ejection fraction, history of ischemic cardiomyopathy and combination with antiplatelet, the thrombus resolution among the two groups remained similar.

Safety and efficacy of non-vitamin K antagonist oral anticoagulants compared with well-controlled warfarin in Thai patients with atrial fibrillation.

In trials of patients with atrial fibrillation (AF), non-vitamin K antagonist oral anticoagulants (NOACs) were not inferior to warfarin for thromboembolic and bleeding events. However, there are scant data comparing the efficacy and safety of NOACs in patients with AF with that of well-controlled warfarin treatment in such patients. To compare total bleeding and thromboembolic events in patients with AF who received NOACs, with the same events in those who received well-controlled warfarin treatment. We used retrospective data from patients with AF who received NOACs or well-controlled warfarin at the Central Chest Institute of Thailand from January 2017 to December 2019. The primary outcome was total bleeding or thromboembolic events or both. The secondary outcome was all-cause mortality, total bleeding events including major or minor bleeding, and thromboembolic events including ischemic stroke or systemic embolization. We included data from 180 patients with AF, 90 who received NOACs and 90 who received well-controlled warfarin. The average time in the therapeutic range for those who received warfarin was 84.9% ± 9.8%. The patients who received well-controlled warfarin had more frequent thromboembolic or total bleeding events or both than those who received NOACs (odds ratio [OR] 3.17; 95% confidence interval [CI] 2.27-4.07; P = 0.01). There were more minor bleeding events in those who received well-controlled warfarin (OR 3.75; 95% CI 2.79-4.71; P = 0.01). However, there was no significant difference in thromboembolic events, major bleeding, or all-cause mortality between the 2 groups. Thai patients with AF who received NOACs had less thromboembolic or total bleeding events than those who received well-controlled warfarin treatment.

Impact of P-glycoprotein and/or CYP3A4-interacting drugs on the risk-benefit profile of NOACs in patients with atrial fibrillation: a meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO) Background P-glycoprotein (P-gp) and CYP3A4-interacting drugs influence plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs). However, the clinical relevance is questioned. Purpose A critical appraisal of the impact of pharmacokinetically-interacting drugs on the effectiveness and safety of NOACs in patients with atrial fibrillation (AF). Methods After searching Pubmed and Embase, phase III randomized controlled trials (RCTs) and longitudinal observational cohort studies on the impact of concomitantly used P-gp/CYP3A4-interacting drugs on the risk-benefit profile of NOACs in AF patients during a mean/median follow-up of ≥6 months were included. A fixed effects meta-analysis was performed with the Mantel-Haenszel method. Results Fifteen studies were included (10 post hoc analyses of RCTs, 5 observational studies), investigating 21,711 and 306,421 NOAC-treated AF patients with and without P-gp/CYP3A4 inhibitor use respectively, while only one study included P-gp/CYP3A4 inducers. In NOAC-treated AF patients, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding (relative risk (RR) 1.10, 95% confidence interval (CI) (1.01-1.19)) and all-cause mortality risks (RR 1.14, 95%CI (1.05-1.23)) compared to not using P-gp/CYP3A4 inhibitors, while the risks of stroke/SE (RR 0.88, 95%CI (0.77-1.01)), intracranial bleeding (RR 0.89, 95%CI (0.68-1.15)) and gastro-intestinal bleeding (RR 1.09, 95%CI (0.91-1.30)) were not significantly different. Concomitant use of amiodarone with NOACs was associated with lower thromboembolic (RR 0.75, 95%CI (0.61-0.92)), but higher mortality risks (RR 1.21, 95%CI (1.05-1.39)). Co-administration of verapamil or diltiazem was associated with higher major bleeding risks (RR 1.64, 95%CI (1.31-2.06)), but no significantly different thromboembolic or mortality risks. Conclusions Given the higher bleeding and mortality risks in NOAC-treated AF patients concomitantly using P-gp/CYP3A4 inhibitors compared to NOAC users not taking interacting drugs, close monitoring of these patients is warranted, including regular medication review and addressing modifiable bleeding risk factors. Regarding P-gp/CYP3A4 inducers, a considerable research gap was identified, necessitating more research on their impact.

Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis.

P-glycoprotein (P-gp) and CYP3A4-interacting drugs influence plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs). However, the clinical relevance is questioned. Therefore, the impact of pharmacokinetically-interacting drugs on the effectiveness and safety of NOACs in patients with atrial fibrillation (AF) was investigated. A meta-analysis was performed based on randomized controlled trials and observational studies retrieved from Pubmed and Embase that investigated the impact of concomitantly used P-gp/CYP3A4-interacting drugs on the risk-benefit profile of NOACs in AF patients. Fifteen studies were included, investigating 21 711 and 306 421 NOAC-treated AF patients with and without P-gp/CYP3A4 inhibitor use respectively, while only 1 study included P-gp/CYP3A4 inducers. In NOAC-treated AF patients, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding (relative risk [RR] 1.10, 95% confidence interval [CI; 1.01-1.19]) and all-cause mortality risks (RR 1.14, 95%CI [1.05-1.23]) compared to not using P-gp/CYP3A4 inhibitors, while the risks of stroke/systemic embolism (RR 0.88, 95%CI [0.77-1.01]), intracranial bleeding (RR 0.89, 95%CI [0.68-1.15]) and gastrointestinal bleeding (RR 1.09, 95%CI [0.91-1.30]) were not significantly different. Concomitant use of amiodarone with NOACs was associated with lower thromboembolic (RR 0.75, 95%CI [0.61-0.92]), similar major bleeding (RR 0.92, 95%CI [0.80-1.07]) but higher mortality risks (RR 1.21, 95%CI [1.05-1.39]). Coadministration of verapamil or diltiazem was associated with higher major bleeding risks (RR 1.64, 95%CI [1.31-2.06]), but comparable thromboembolic (RR 1.10, 95%CI [0.75-1.61]) and mortality risks (RR 1.01, 95%CI [0.77-1.33]). Given the higher bleeding and mortality risks in NOAC-treated AF patients concomitantly using P-gp/CYP3A4 inhibitors, close monitoring is warranted.

Non-Vitamin K Oral Anticoagulants Assessment in High Risk of Bleeding Patients with Non-Valvular Atrial Fibrillation.

Atrial fibrillation (AF) is commonly associated with advanced age and the presence of multiple, concomitant acute and chronic health conditions, placing this population at high risk for serious therapeutic side effects. Nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in patients with atrial fibrillation. The purpose of this study was to investigate the effectiveness and safety of NOAC in a group at high risk of bleeding complications, in a real-world setting. We conducted a retrospective analysis of a high-risk cohort of 418 patients (pts) followed-up in our anticoagulation unit; data on patient characteristics, anticoagulation treatment, and bleeding and thrombotic complications were evaluated. The population had a median age of 77.8 ± 10.3 years and the mean CHA2DS2-VASc score was 3.85 (SD ± 1.4). Overall, 289 (69.1%) were ≥75 years old. During a mean follow-up time of 51.2 ± 35.7 months, we observed a rate of any bleeding of 7, a clinically relevant non-major bleeding rate of 4.8, a major bleeding rate of 2.2, a stroke rate of 1.6, and a rate of thrombotic events of 0.28 per 100 patient-years. There were 59 hospitalizations due to any cause (14.1%) and 36 (8.6%) deaths (one due to ischemic stroke). A structured follow-up, with judicious prescribing and drug compliance, may contribute to preventing potential complications.

Comparative effectiveness of NOAC vs VKA in patients representing common clinical challenges: results from the GARFIELD-AF registry

Abstract Introduction Large phase III trials of non-valvular atrial fibrillation (AF) patients have shown a favourable risk-to-benefit ratio with Non-Vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin K antagonists (VKA). Although the results of these trials are directly applicable to many AF patients, important subsets of patients were under-represented. Thus, there remains uncertainty about the safety and effectiveness of NOAC therapy in common challenging scenarios. Purpose The main purpose of this study is to quantify and compare the impact of NOAC vs VKA in settings where clinical uncertainty still exists and represents a considerable proportion of AF patients in clinical practice. Methods The analysis was conducted in patients enrolled in the largest AF multinational prospective registry (the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation, GARFIELD-AF). We evaluated the effectiveness and safety of NOAC compared to VKA in three groups of patients representing common clinical challenges (CCC): 1) elderly patients (i.e. age ≥75), 2) increased bleeding risk (i.e. HAS-BLED ≥3 or prior bleeding), and 3) renal impairment (i.e. CKD stages II to IV). We applied a propensity score using an overlap weighting scheme to obtain unbiased estimates of the treatment effect within each CCC group. Weights were applied to Cox proportional hazards models to estimate the effects of the NOAC vs VKA comparison on the occurrence of death, non-haemorrhagic stroke/SE and major bleeding within 2 years of enrolment. Results Comparative effectiveness of NOAC vs VKA was assessed in 8607 elderly patients, 1711 with increased bleeding risk, and 4460 with renal impairment. The proportion of anticoagulated patients was low in patients with increased bleeding risk (59%), while in the other two CCC groups the corresponding proportion was close to the one in the overall population (72%). Among anticoagulated patients, NOAC were prescribed to 50–55% of patients in the CCC groups. Patients with a high risk of bleeding and impaired kidney function were less likely to be prescribed NOAC instead of VKA compared with the overall anticoagulated population (−5.4% and −4.7%, respectively). Propensity-weighted hazard ratios for all-cause mortality favored NOAC (vs VKA) in all three CCC groups: 0.86 (95% CI: 0.74–0.99) for elderly patients, 0.73 (0.53–1.00) for patients with increased bleeding risk, and 0.80 (0.65–0.98) for patients with renal impairment (Figure). Conclusion In the selected common challenging scenarios of AF patients, there were significant mortality reductions in favor of NOACs compared to VKAs. These observations suggest that NOACs are safe and effective in patients who are elderly, at increased bleeding risk, or renally impaired. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. The work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer in Real World: Meta-Analysis of Retrospective Observational Studies

Background: Evidence on the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer. Methods: The PubMed and Embase databases were searched up to June 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) using a random-effects model. Results: A total of five observational studies involving 232,234 cancer patients with AF were included. Compared with VKAs, use of NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.79; 95% CI 0.69-0.90), is chaemic stroke (RR, 0.82; 95% CI, 0.72-0.93), venous thromboembolism (VTE) (RR, 0.28; 95% CI 0.14-0.53), all-cause death (RR, 0.57; 95% CI 0.50-0.64), major bleeding (RR, 0.60; 95% CI 0.51-0.72) and intracranial or gastrointestinal bleeding (RR, 0.61; 95% CI, 0.51-0.73). Conclusions: In this combined analysis of real-world observational studies, NOACs showed lower risks of stroke or systemic embolism, ischaemic stroke, VTE, all-cause death and reduced rates of major bleeding and intracranial or gastrointestinal bleeding compared to VKAs in patients with AF and cancer.

Nonvitamin K Antagonist Oral Anticoagulant in Patients With Venous Thromboembolism and Polycythemia Vera or Essential Thrombocythemia: A Cohort Study.

Thrombosis is the most common adverse event in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Little is known about the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with myeloproliferative neoplasms. We sought to evaluate the efficacy and safety of NOAC in a cohort of patients with PV and ET, who experienced venous thromboembolism (VTE). We enrolled 48 consecutive patients with PV (70.8%) and ET [median age 67.0 (interquartile range, 58.5-72.0) years], who experienced VTE. Patients received apixaban (39.6%), rivaroxaban (33.3%), or dabigatran (27.1%). During a median follow-up of 30 (interquartile range, 20.5-41.5) months, recurrent thrombotic events and bleeding were recorded. Four thrombotic events (3.3 per 100 patient-years) were reported. Three deep vein thrombosis episodes (2.5 per 100 patient-years) were experienced by 2 patients with PV, who received apixaban (5 mg bid) and dabigatran (150 mg bid), and 1 patient with ET, who received dabigatran (150 mg bid). One ischemic stroke occurred in a patient with PV on rivaroxaban (20 mg/d). There was 1 major bleeding (0.8 per 100 patient-years) in a patient with ET on dabigatran (150 mg bid) and 3 clinically relevant nonmajor bleeding (2.5 per 100 patient-years): 2 on rivaroxaban (20 mg/d) and 1 on apixaban (5 mg bid). We did not observe significant differences related to the type of NOAC. Three deaths (2.5 per 100 patient-years) unrelated to either VTE or bleeding were recorded. This study shows that NOACs may be effective and safe as secondary prevention of VTE in patients with myeloproliferative neoplasms.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer in Real World: Meta-Analysis of Retrospective Observational Studies

Background: Evidence on the safety and effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Atrial Fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer.

P4780Effectiveness and safety of non-vitamin k antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease

Abstract Background Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice. Purpose To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD. Methods We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups. Results After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53–0.96), GI bleeding (HR 0.50, 95% CI 0.35–0.72) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome. Clinical outcome in AF patients with VHD Conclusion In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.

Number needed to treat based on real-world evidence for non-vitamin K antagonist oral anticoagulants versus vitamin K antagonist oral anticoagulants in stroke prevention in patients with non-valvular atrial fibrillation

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) are used to prevent stroke in patients with atrial fibrillation (AF). This paper aimed to evaluate the clinical efficacy and safety of NOACs when compared to VKAs by calculating the number needed to treat (NNT) at 2 years using incidence rates and hazard ratios (HRs) derived from a meta-analysis of studies conducted in real-world settings. Materials and methods: HRs were sourced from a published systematic literature review and a meta-analysis of real-world evidence on the use of NOACs vs VKAs. Rivaroxaban, dabigatran, and apixaban vs VKAs were investigated. The efficacy outcomes included: a composite of ischaemic stroke and systemic embolism (IS/SE), ischaemic stroke (IS), and all-cause mortality. The safety analysis assessed major bleeding and intracranial haemorrhage (ICH). Results: Superiority of NOACs vs VKAs was observed in 10/15 comparisons. Treating patients with rivaroxaban and dabigatran was associated with a reduced risk of IS and all-cause mortality compared to VKAs, with one death prevented every 22 and 32 patients, respectively, and one IS prevented every 206 and 166 patients, respectively. Rivaroxaban was significantly associated with a reduced risk of IS/SE compared to VKA (NNT: 107). No significant differences were observed between apixaban and VKAs. Dabigatran and apixaban were associated with a reduced risk of major bleeding compared to VKA (NNT: 59 and 38, respectively). No significant difference was observed between rivaroxaban and VKAs regarding major bleeding. Rivaroxaban, dabigatran, and apixaban were significantly associated with a reduced risk of ICH (NNT: 205, 115, and 108, respectively). Limitations: Heterogeneity in definitions of major bleeding across studies. Conclusions: The NNT calculation, when approached and interpreted properly, is a practical measure of the effectiveness of a treatment. The calculation based on HRs showed that NOACs are safe and effective alternatives to VKAs in real life.

Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis

BackgroundAmiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk atrial fibrillation (AF) patients. We studied efficacy and safety of NOACs in AF patients receiving amiodarone, P-glycoprotein inhibitor, or polypharmacy. MethodsAfter a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), four phase-III randomized trials comparing NOACs and warfarin in “with/without amiodarone,” “with/without P-glycoprotein inhibitors,” or “with/without multiple (≥5, polypharmacy) concomitant drugs” subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risks (RRs) for stroke/systemic thromboembolism (SSTE), major bleeding (MB), intracranial hemorrhage (ICH), and all-cause mortality. ResultsAmong patients taking amiodarone, superiority of NOACs over warfarin in non-amiodarone users disappeared in terms of SSTE (p=0.11), MB (p=0.95), ICH (p=0.26), and mortality (p=0.32). No safety benefit (MB) of NOACs compared to warfarin was shown in patients taking P-glycoprotein inhibitors (p=0.47), but SSTE prevention was still superior with NOACs compared to warfarin in the same patient group [RR=0.78 (0.61–0.99), p=0.04, I2=11%]. In AF patients with polypharmacy, NOACs showed a lower risk of SSTE [RR=0.82 (0.71–0.96), p=0.01, I2=0%] and mortality [RR=0.91 (0.83–0.99), p=0.04, I2=0%], but not MB (p=0.81) compared to warfarin. ConclusionsNOACs were equivalent to warfarin among AF patients with concomitant amiodarone use in terms of efficacy, safety, and mortality. There was no safety benefit of NOACs over warfarin in patients using polypharmacy or P-glycoprotein inhibitors. Systematic review registrationThe protocol of this meta-analysis was registered on PROSPERO under CRD42018104808 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42018104808).

Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Thrombocytopenia.

Thrombocytopenia was one of the exclusion criteria in randomized trials in which non-vitamin K antagonist oral anticoagulants (NOACs) were tested. The safety of NOACs in patients with atrial fibrillation (AF) and thrombocytopenia remains unclear. We studied 62 patients with AF aged from 53 to 85 (mean 70.5) years with platelet count from 50 to 100 × 109/L who were treated with rivaroxaban 15 mg once daily (33.9%), dabigatran 110 mg twice daily (bid) (54.8%), or apixaban 2.5 mg bid (11.3%). Age- and sex-matched AF patients with normal platelet count and similar CHA2DS2-VASc scores who were treated with the recommended doses of NOACs served as a reference group. Patients were followed for a mean of 55 months (range, 23-64 months). In the thrombocytopenia group bleeding risk was higher (mean HAS-BLED score 2.0, vs. 1.0, P < 0.0001). During follow-up in thrombocytopenic and normocytopenic patients, we observed similar rates of major bleeding (1.8%/year vs. 2.7%/year, P = 0.49), clinically relevant nonmajor bleeding (CRNMB) (1.5%/year vs. 1.1%/year, P = 0.74), ischemic stroke and transient ischemic attacks (1.8%/year vs. 1.5%/year, P = 0.8), and death (1.06%/year vs. 1.11%/year, P = 0.96). The risk of bleeding and stroke was unaffected by the type of the NOAC used in both groups. Major bleedings and clinically relevant nonmajor bleeding in thrombocytopenic patients on NOACs were predicted only by age (hazard ratio 1.1, 95% confidence interval 1.0-1.3, P = 0.04). Our findings indicate that in AF patients with mild thrombocytopenia, anticoagulation with NOAC at reduced doses seems to be safe and effective.

Atrial Fibrillation and Malignancy: The Clinical Performance of Non-Vitamin K Oral Anticoagulants-A Systematic Review.

Atrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2DS2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: ARetrospective Cohort Study.

BackgroundPatients with impaired liver function (ILF) were excluded from clinical trials that investigated non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOACs in atrial fibrillation patients with ILF.Methods and ResultsA cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOACs and warfarin in patients with normal liver function and ILF, respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65–0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60–0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF, compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49–0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding.ConclusionsIn atrial fibrillation patients with ILF, NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction.

Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly prevalent in the general population and share common risk factors such as older age, hypertension and diabetes mellitus. The presence of CKD increases the risk of incident AF, and, likewise, AF increases the risk of CKD development and/or progression. Both conditions are associated with substantial thromboembolic risk, but patients with advanced CKD also exhibit a paradoxical increase in bleeding risk. In the landmark randomized clinical trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for thromboprophylaxis in patients with AF, the efficacy and safety of NOACs in patients with mild-to-moderate CKD were similar to those in patients without CKD. Dose adjustment of NOACs as per the prescribing label is required in this population. Owing to limited trial data, evidence-based recommendations for the management of patients with AF and severe CKD or end-stage renal disease on dialysis are lacking. Observational cohort studies have reported conflicting results, and the management of these particularly vulnerable patients remains challenging and requires careful assessment of stroke and bleeding risk and, where appropriate, use of warfarin with good-quality anticoagulation control.