Positive Net Clinical Benefit Research Articles

Anticoagulation therapy in non-valvular atrial fibrillation after intracerebral hemorrhage: A propensity score–matched study

BackgroundThe effect of antithrombotic therapy on patients with atrial fibrillation who sustained previous intracerebral hemorrhage (ICH) remains uncertain. Data regarding antithrombotic therapy use in these patients are limited. This study aims to compare the clinical and overall outcomes of antithrombotic therapy and usual care in patients with atrial fibrillation who sustained ICH. MethodsWe assembled consecutive patients with atrial fibrillation sustaining an ICH from our institution. Multivariable regression analysis and propensity-matched analysis were applied to assess associations of different antithrombotic therapies and outcomes. The primary outcome was mortality within the longest follow-up. Kaplan-Meier curves and log-rank tests of the time-to-event data were used to assess differences in survival. ResultsIn total, 296 consecutive patients with atrial fibrillation who survived an ICH were included in this study. Our analysis demonstrated that antithrombotic therapy was associated with reduced mortality up to a 4-year duration of follow-up (OR, 0.49, 95 % CI 0.30–0.81). Similar results were obtained from the propensity-matched analysis (OR, 0.58, 95 % CI 0.34–0.98). Subgroup analysis showed that compared with usual care, direct oral anticoagulant (DOAC) with or without antiplatelet was associated with a lower risk of long-term mortality (OR, 0.34, 95 % CI 0.17–0.69). In addition, our analysis observed a significant interaction between cardiac insufficiency and treatment effect (P = 0.04). ConclusionsIn patients with atrial fibrillation who have a history of ICH, administration of antithrombotic therapy, especially DOAC, was associated with lower mortality. Future randomized trials are warranted to test the positive net clinical benefit of DOAC therapy.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis—a nationwide cohort study

BackgroundIn post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies.MethodsThis study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone.ResultsThe risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB.ConclusionsFor post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Net clinical benefit of oral anticoagulants in Asian patients with atrial fibrillation based on a CHA2DS2-VASc score

BackgroundThis study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA2DS2-VASc score.MethodsPatients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA2DS2-VASc score of 0–1 and ≥ 2, respectively. The survival analysis was performed based on CHA2DS2-VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor.ResultsA total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA2DS2-VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA2DS2-VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA2DS2-VASc score. Females with CHA2DS2-VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA2DS2-VASc score of 3 or more.ConclusionsAF patients with CHA2DS2-VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males.

Assessment of clinical and economic impact of rivaroxaban plus aspirin vs. aspirin alone as a secondary prophylaxis in patients with chronic and symptomatic peripheral arterial disease in the United States

AimThe objective in this study was to assess the clinical and economic implications of the inclusion of rivaroxaban as a secondary prophylaxis in patients with chronic or symptomatic peripheral artery disease (PAD) in the United States (US).MethodsA cost-consequence model was adapted to evaluate the economic impact of rivaroxaban plus aspirin in a hypothetical 1-million-member health plan. The model inputs were taken from multiple sources: efficacy and safety of rivaroxaban + aspirin vs. aspirin alone were abstracted from COMPASS and VOYAGER randomized clinical trials; the prevalence of chronic and symptomatic PAD and incidence rates of clinical events (major adverse cardiac events [MACE], major adverse limb events [MALE], and major bleeding), were abstracted from the analysis of claims data; healthcare costs of clinical events and wholesale acquisition costs for rivaroxaban were abstracted from the literature and Red Book, respectively (2022 USD). One-way sensitivity analyses and subgroup analyses were also conducted.ResultsOver one year, with a 5% uptake of rivaroxaban, the model estimated rivaroxaban + aspirin to reduce 21 MACE/MALE events in the PAD patient population. The reduction in these clinical events offsets the increased risk of major bleeding (16 additional events), demonstrating a positive health benefit of the rivaroxaban addition. These benefits led to a $0.27 incremental cost per member per month (PMPM) to a US plan. The major driver of the incremental cost was the cost of rivaroxaban. In a subgroup of patients with the presence of any high-risk factor (heart failure, diabetes, renal insufficiency, or history of vascular disease affecting two or more vascular beds), the incremental PMPM cost was $0.13.ConclusionsRivaroxaban + aspirin was found to provide positive net clinical benefit on the annual number of MACE/MALE avoided, with a modest increase in the PMPM cost.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis - A nationwide cohort study

Abstract Background In post-stroke AF patients with indications for both oral anticoagulants (OACs) and antiplatelet agents (AP), eg. those with carotid artery stenosis, there is debate over the best management strategy. Objectives We aimed to examine outcomes in post-stroke AF patients with extracranial artery stenosis (ECAS). Second, to explore stroke and bleeding outcomes as well as the net clinical benefit (NCB), with OACs (non-vitamin K antagonist OACs [NOACs] or warfarin) and with AP-OAC combination therapy, when compared to AP alone. Methods We performed a nationwide cohort study in post-stroke AF patients with and without ECAS (n=6390 and 28093, respectively). The risks of clinical events and NCB with different antithrombotic strategies were compared to AP alone. Results The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, p&amp;lt;1.001). For patients with ECAS, when compared to AP only, NOAC monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551 [95%CI 0.454-0.669], the composite of ischaemic stroke/major bleeding (aHR 0.577 [95%CI 0.478-0.697]) and the composite of ischaemic stroke/ICH (aHR 0.577 [95%CI 0.478-0.697]), with nonsignificant difference for major bleeding and ICH (Figure). NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination AP-OACs) were associated with negative NCB. Conclusions For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Effect of extended duration of thromboprophylaxis for medically ill patients

BackgroundThere are knowledge gaps regarding the comparative efficacy and safety of various venous thromboprophylaxis regimens with extended timing in patients hospitalized for acute medical illnesses. This study aims to investigate the optimal regimen for the prevention of venous thromboembolism in these patients. MethodsWe conducted a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing different venous thromboprophylaxis regimens for acutely ill medical patients. Outcomes included venous thromboembolism, major bleeding, and all-cause mortality. Risk ratios (RR) and associated 95% credible interval (CrI) were estimated. In addition, we assessed the most effective interventions in a subgroup of patients with stroke. ResultsWe identified five RCTs involving 40,124 patients. Extended thromboprophylaxis with direct oral anticoagulant (DOAC) (RR 0.78, 95% CrI 0.68 to 0.89) and low molecular weight heparin (LMWH) (RR 0.62, 95% CrI 0.45 to 0.84) were superior to standard therapy in the prevention of venous thromboembolism. However, both of them (DOAC: RR 1.99, 95% CrI 1.38 to 2.92; LMWH: RR 2.56, 95% CrI 1.26 to 5.68) lead to a significant increase in major bleeding). Moreover, both LMWH (RR 0.76, 95% CrI 0.57 to 1.00) and DOAC (RR 0.86, 95% CrI 0.76 to 0.98) with extended thromboprophylaxis showed favorable net clinical benefit compared to standard therapy. ConclusionsExtended thromboprophylaxis, especially with LMWH, showed better efficacy in venous thromboembolism reduction with increased risk of major bleeding. The beneficial effect of LMWH with extended timing has also been shown in stroke patients. Overall, extended thromboprophylaxis is associated with a positive net clinical benefit.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score=0). In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

Net clinical benefit of antithrombotic therapy for atrial fibrillation patients with stable coronary artery disease.

ObjectivesTo compare the net clinical benefit of oral anticoagulant (OAC) monotherapy to OAC plus single antiplatelet therapy (SAPT) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) at 1- and 3-year after percutaneous coronary intervention (PCI).BackgroundIt has not been studied whether the net clinical benefit of the antithrombotic treatment options differs depending on the elapsed time from the index PCI.MethodsUsing the Korean nationwide claims database, we included AF patients who underwent PCI from 2009 to 2019 and constructed two cohorts: 1- and 3-year after PCI. In each cohort, the baseline characteristics of two groups were balanced using propensity score weighting. Ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes were analyzed.ResultsAmong patients with 1-year after PCI, OAC monotherapy (n = 678), and OAC plus SAPT (n = 3,159) showed comparable results for all clinical outcomes. In patients with 3-year after PCI, OAC monotherapy (n = 1,038) and OAC plus SAPT (n = 2,128) showed comparable results for ischemic stroke and myocardial infarction, but OAC monotherapy was associated with a lower risk of composite clinical outcomes (HR 0.762, 95% CI 0.607–0.950), mainly driven by the reduction of major bleeding risk (HR 0.498, 95% CI 0.345–0.701).ConclusionOral anticoagulant monotherapy may be a comparable choice for patients with AF and stable CAD compared to OAC plus SAPT. In patients with stable CAD more than 3-year after index PCI, OAC monotherapy would be a better choice, being associated with less major bleeding and a positive net clinical benefit.

Clinical Performance of Oral Anticoagulants in Elderly with Atrial Fibrillation and Low Body Weight: Insight into Italian Cohort of PREFER-AF and PREFER-AF Prolongation Registries.

Background: Elderly patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus well-controlled vitamin-K antagonists (VKA) therapy among AF patients aged >75 years and with a body weight <60 kg in a prospective registry setting. Methods: Data for this study were sourced from the Italian cohorts of PREFER in AF and PREFER in AF PROLONGATION registries. The occurrence of a composite of stroke, transient ischemic attack and systemic embolism (thromboembolic events) was the primary effectiveness endpoint. The occurrence of major bleeding was the primary safety endpoint. All-cause hospitalizations and all-cause death were the secondary endpoints. The net clinical benefit (NCB) was calculated in order to obtain an integrated assessment of the anti-thromboembolic and pro-haemorrhagic effects of NOACs vs. VKA. Results: Overall, 522 patients were included; 225 were on treatment with NOACs and 317 patients with VKA. The NOAC group more frequently featured a higher BMI and a higher prevalence of history of stroke/TIA and insulin-requiring diabetes; conversely, heart failure and chronic liver disease were less frequent in the NAOC group. In the unmatched study population, 18 patients (3.6% in the NOAC vs. 3.2% in the VKA group, p = 0.79) experienced thromboembolic events; 19 patients (1.78% in the NOAC vs. 4.73% in the VKA group, p = 0.06) experienced major bleeding events; and 68 patients were hospitalized during the follow-up (9.3% vs. 14.8%, p = 0.06). After balancing for potential confounders by using the 1:1 propensity score matching technique, 426 patients (213 on NOAC and 213 on VKA) were selected. We found no significant differences in terms of thromboembolic events (3.76% vs. 4.69%, p = 0.63), major bleeding events (n: 1.88% vs. 4.22%, p = 0.15) and hospitalizations (9.9% vs. 16.9%, p = 0.06) between NOAC vs. VKA matched population. Based on these incidences, we found a positive net clinical benefit (+1.6) of NOACs vs. VKAs. Conclusions: These real-world data suggest the safety and effectiveness of using NOACs in elderly patients with low body weight.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study.

AimsThere is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant.Methods and resultsWe conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56–0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54–1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59–1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88–2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70–1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42–0.94).ConclusionThese observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial.

Antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease of 1-year and 3-year after percutaneous coronary intervention: a nationwide population-based study

Abstract Background In a recent trial, rivaroxaban monotherapy was noninferior for efficacy and superior for safety to rivaroxaban plus single antiplatelet therapy, as antithrombotic therapy for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, there are limited data regarding the comparative effectiveness and safety of oral anticoagulant (OAC) monotherapy versus OAC plus single antiplatelet therapy (SAPT) in real-world practice, especially after the introduction of direct oral anticoagulants (DOAC). Purpose To compare the effectiveness, safety, and net clinical benefit of OAC monotherapy to OAC plus SAPT in patients with AF and stable CAD of 1-year and 3-year after percutaneous coronary intervention (PCI) in a contemporary real-world observational cohort. Methods Using the Korean nationwide claims database, we included AF patients who underwent PCI from January 1, 2009 to February 28, 2019. Considering dynamic changes of antithrombotic therapy according to the period after receiving PCI, the index antithrombotic treatment was independently defined at the different time after receiving PCI and we conducted two cohort: 1-year and 3-year after PCI. In each cohort, the baseline characteristics of OAC monotherapy and OAC plus SAPT groups were balanced using inverse probability of treatment weighting (IPTW) methods. To assess clinical outcomes, ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes of each outcome were analyzed. Results In cohort with 1-year after PCI, 678 patients with OAC monotherapy and 3159 patients with OAC plus SAPT were included. In cohort with 3-year after PCI, 1038 patients with OAC monotherapy and 2128 patients with OAC plus SAPT were enrolled. The baseline characteristics were well-balanced after IPTW between the two groups in both cohorts. Among total population, about 45% of patients prescribed DOAC as OAC treatment. Among patients with 1-year after PCI, OAC monotherapy and OAC plus SAPT showed comparable results for ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes (Figure). In cohort with 3-year after PCI, OAC monotherapy and OAC plus SAPT showed comparable results for ischemic stroke and myocardial infarction, but OAC monotherapy was associated with a lower risk of the composite clinical outcome (hazard ratio [HR] 0.762, 95% confidence interval [CI] 0.607–0.950), mainly driven by reduction of major bleeding risk (HR 0.762, 95% CI 0.607–0.950) compared to OAC plus SAPT (Figure). Conclusion OAC monotherapy might be, at least, comparable choice for patients with AF and stable CAD compared to OAC plus SAPT. In patients with stable CAD more than 3-years after index PCI, OAC monotherapy could be better therapeutic choice to achieve less major bleeding and positive net clinical benefit. Funding Acknowledgement Type of funding sources: None.

Oral anticoagulation therapy with rivaroxaban in elderly patients with atrial fibrillation. Results from EMIR study

Abstract Background Atrial fibrillation (AF) in elderly patients increases both bleeding and thromboembolic risks. Elderly patients benefit as much from anticoagulation therapy with positive net clinical benefit. However, there have been few studies that focused on the efficacy and safety of direct oral anticoagulants in elderly patients. The aim of this subanalysis from EMIR study was to assess the effectiveness of rivaroxaban in patients older than 75 years old. Methods EMIR Study (acronym from 'Estudio observacional para la identificaciόn de los factores de riesgo asociados a eventos cardiovasculares Mayores en pacientes con fIbrilaciόn auricular no valvular tratados con un anticoagulante oral directo (Rivaroxaban)') was an observational, multicenter, post-authorization and prospective study that involved AF patients under oral anticoagulation with rivaroxaban at least 6 months before enrolment. We analyzed baseline clinical characteristics and adverse events after 2.5 years of follow up. Results We analyzed 1,433 patients with median age of 74.7 (67.7–81.6). Of them 691 (48.2%) were ≥75 years. Elderly patients had higher prevalence of cardiovascular risk factors such previous stroke (16.8% vs 8.5%; p&amp;lt;0.001), heart failure (25.0% vs 20.6%; p&amp;lt;0.001), higher CHA2DS2-VASc (4.4±1.3 vs 2.7±1.2; p&amp;lt;0.001) and HAS-BLED (1.9±1.0 vs 1.2±1.0; p&amp;lt;0.001) scores. After 2.5 (2.2–2.6) years of follow-up, we observed low rate of adverse events in patients under rivaroxaban therapy. We observed higher rate of adverse events in elderly population for thromboembolic events (1.13%/year vs 0.36%/year; p=0.017) and major bleeding events (1.80%/year vs 0.36%/year; p&amp;lt;0.001) but those adverse rates were lower than expected according to previous studies (i.e. ROCKET-AF trial, rivaroxaban group had 4.86%/year of major bleeding or in XANTUS study was 3.2%/year of major bleeding in patients &amp;gt;75 years). We did not observe differences between groups from MACE (1.13%/year vs 1.01%/year; p=0.875) or cardiovascular death (0.86%/year vs 0.42%/year; p=0.170). Conclusion In real-world elderly population, rivaroxaban showed higher rates of thromboembolic and major bleeding events in elderly patients but with annual rates lower than expected according to previous studies like ROCKET-AF or XANTUS. Similar annual rates in elderly were observed for MACE and cardiovascular mortality than in younger patients, being rivaroxaban a good therapeutic alternative even for the elderly. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Hispania S.L.

Net clinical benefit of direct oral anticoagulants in very elderly and high bleeding risk patients with atrial fibrillation who are often excluded from oral anticoagulation therapy: a nationwide popul

Abstract Background In the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial, low-dose edoxaban (15mg once daily) showed better efficacy for stroke prevention and positive net clinical benefit compared to placebo in very elderly and high bleeding risk patients with atrial fibrillation (AF) who often excluded from oral anticoagulation (OAC) therapy. However, there are limited data to generalize the ELDERCARE-AF results into daily practice. Purpose To investigate the optimal OAC strategy for the best net clinical benefit in ELDERCARE-AF-like patients. Methods Using the Korean nationwide claims database, we included patients with incident non-valvular AF aged 80 years or older between 2014 and 2017. Among these, patients with one or more of the following criteria were finally included in the analysis: a low creatinine clearance (15 to 30 mL/min), a history of bleeding from a critical area or organ or gastrointestinal bleeding, low body weight (≤45kg), continuous use of nonsteroidal anti-inflammatory drugs, or current use of an antiplatelet drug. The risks of ischemic stroke, major bleeding, all-cause death, and composite clinical outcome (ischemic stroke+major bleeding+all-cause death) as a measure of net clinical outcome were evaluated during follow-up. The inverse probability of treatment weighting (IPTW) method was used to balance covariates between the groups. Results A total of 23,858 patients were finally included (no OAC, n=16,575; warfarin, n=2390; and direct oral anticoagulants (DOACs), n=4893, respectively). Among DOAC group, 69% used low-dose including rivaroxaban 15 mg once daily, dabigatran 110 mg twice daily, apixaban 2.5 mg twice daily, and edoxaban 30 mg once daily and 9% used very low dose including rivaroxaban 10 mg once daily and edoxaban 15 mg once daily (Figure). Median follow-up duration was 2 years (interquartile ranges, 1 to 3 years). Baseline characteristics were well-balanced after IPTW. Compared to the no OAC group, the DOAC group was associated with a lower risk of ischemic stroke (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68–0.95) and all-cause death (0.90, 0.85–0.95), and a higher risk of major bleeding (1.43, 1.20–1.69) (Figure). Patients treated with DOAC showed a lower risk of composite clinical outcome compared to those without OAC treatment (0.93, 0.88–0.98). Warfarin treatment did not reduce the risk of ischemic stroke (1.03, 0.85–1.23) and all-cause death (1.05, 0.99–1.12), but increased the risk of major bleeding (1.60, 1.32–1.92) and the composite clinical outcome (1.08, 1.02–1.15) compared to no OAC group. Conclusion In very elderly patients with non-valvular AF who had one or more frail components, DOACs which were currently prescribed in usual clinical practice showed better effectiveness and positive net clinical benefit compared to no OAC treatment. Compared to the latter, warfarin did not show benefit and possible harm. Funding Acknowledgement Type of funding sources: None.

Effect of anti-coagulation in elderly patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation has been shown to associate with greater cognitive decline and increased dementia risk independent of ischaemic stroke. Anti-coagulation was associated with a lower risk of ischemic stroke and positive net clinical benefit in elderly patients in Asian populations. We hypothesise that elderly patients (&amp;gt;75 years old) with atrial fibrillation on oral anti-coagulants have lower incidence of dementia compared with patients on anti-platelet agents or no anti-thrombotic treatment. Method A retrospective study of 747 patients, male 37%, mean age 84.29 ± 5.99 years old with mean follow up of 13.54 ± 3.38 years. 94 % hypertension, 40% diabetes mellitus, 38% ischaemic heart disease, 33% heart failure, 39% previous stroke, mean CHA2DS2-VASc score of 5.23 ± 1.59. 27% patients on oral anti-coagulants, 64% anti-platelet agent and 9% not on any anti-thrombotic medication. Results 265 patients were diagnosed with dementia, 17 patients were on oral anti-coagulants, 222 patients were on anti-platelet agent. Oral anti-coagulants were associated with lower incidence of dementia compared with anti-platelet agents (p &amp;lt; 0.0001). 26 patients developed dementia were not on any anti-thrombotic agent. 261 patients were readmitted with stroke (2.58%/100 patient year) 182 patients were on anti-platelet agent while 12 were on anti-coagulant (P &amp;lt; 0.0001). Conclusions Oral anti-coagulants were associated with lower incidence of dementia and stroke compared with anti-platelet agents in elderly patients with atrial fibrillation.

Prevention of stroke and dementia in elderly patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation has been shown to associate with greater cognitive decline and increased dementia risk independent of ischaemic stroke. Anti-coagulation was associated with a lower risk of ischemic stroke and positive net clinical benefit in elderly patients. We hypothesise that elderly patients (&amp;gt;75 years old) with atrial fibrillation on oral anti-coagulants have lower incidence of dementia compared with patients on anti-platelet agents or no anti-thrombotic treatment. Method A retrospective study of 747 patients, male 37%, mean age 84.29 ± 5.99 years old with mean follow up of 13.54 ± 3.38 years. 94 % hypertension, 40% diabetes mellitus, 38% ischaemic heart disease, 33% heart failure, 39% previous stroke, mean CHA2DS2-VASc score of 5.23 ± 1.59. 27% patients on oral anti-coagulants, 64% anti-platelet agent and 9% not on any anti-thrombotic medication. Results 265 patients were diagnosed with dementia, 17 patients were on oral anti-coagulants, 222 patients were on anti-platelet agent. Oral anti-coagulants were associated with lower incidence of dementia compared with anti-platelet agents (p &amp;lt; 0.0001). 26 patients developed dementia were not on any anti-thrombotic agent. 261 patients were readmitted with stroke (2.58%/100 patient year) 182 patients were on anti-platelet agent while 12 were on anti-coagulant (P &amp;lt; 0.0001). Conclusions Oral anti-coagulants were associated with lower incidence of dementia and stroke compared with anti-platelet agents in elderly patients with atrial fibrillation.

Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.

The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.

Oral anticoagulation and cardiovascular outcomes in patients with atrial fibrillation and chronic kidney disease in Asian Population, Data from the COOL-AF Thailand registry

Background and objectivesPatients with AF and chronic kidney disease(CKD) encountered increased risks of stroke, bleeding, morbidity, and overall mortality. Oral anticoagulation in these populations definitely enhances major bleeding but the benefit of stroke reduction remained inconclusive.The aim of this study is to evaluate the effect of oral anticoagulation (OAC) on the 2-year cardiovascular outcomes in patients with AF and CKD. MethodNVAF patients were consecutively enrolled from 27 hospitals located all across Thailand.Baseline demographic and clinical data were collected within 6 months from enrollment.GFR was calculated using CKD-EPI formula. CKD patients were defined as GFR less than 60 mL/min/1.73 m2 according to KDOQI of the National Kidney Foundation. Clinical outcomes included ischemic stroke or transient ischemic attack (TIA) and major bleeding. ResultsAt 25.7 ± 10.6 months of follow up, we identified 2538 patients with complete renal follow-up data. Among these were 1594 patients with CKD (stage 3–5) and 944 patients without CKD. The rate of ischemic stroke in patients with and without CKD were 3.7% and 1.7% respectively (p = 0.004),the rate of major bleeding was 5.6 and 3.5% accordingly (p = 0.015) and, likewise, the death rate was substantially high in patients with CKD (10.0% and 6.5%, p = 0.02). The rate of ischemic stroke/TIA in patients with CKD who were and were not on OAC did not differ significantly, 3.6% and 4.2% respectively (p = 0.602). NOAC and warfarin did not differ significantly in the propensity score-matched rate of both ischemic stroke/TIA (0 and 1.2%, p = 0.554) and major bleeding (3.3% and 7.4%, p = 0.122).The net clinical benefit of NOAC over warfarin was 2.153 per 100-patient years. ConclusionsCOOL AF registry demonstrated that AF patients with CKD had increased risks of ischemic stroke/TIA, major bleeding and death. The benefit of stroke/TIA reduction was not significantly evident for either warfarin or NOAC. However, NOAC was associated with the positive net clinical benefit over no OAC.

Clinical Outcome of Edoxaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation and Diabetes Mellitus: Results from a Multicenter, Propensity-Matched, Real-World Cohort Study.

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 ± 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59; 95% confidence interval (CI), 0.14 to 2.52; p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43; 95% CI: 0.10 to 1.40; p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49; 95% CI: 0.05 to 5.54; p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE; moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.

Clinical Benefit of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves

PurposeThe use of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and bioprosthetic heart valve is still controversial. The aim of this study was to compare the tolerability and effectiveness of treatment with DOACs versus vitamin K antagonists (VKAs) in patients with AF and a bioprosthetic heart valve in clinical practice. MethodsData for this study were sourced from the multicenter, prospectively maintained AF Research Database (NCT03760874), which includes all patients with AF undergoing follow-up at participating centers through outpatient visits every 3–6 months. The rates of occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, systemic embolism), major bleed, and intracranial hemorrhage (ICH) were assessed. These data were used for quantifying the net clinical benefit (NCB) of DOACs versus VKAs, in accordance with the following formula: (Thromboembolic events incidence rate with VKAs – Thromboembolic events incidence rate with DOACs) – Weighting factor × (ICH rate with DOACs – ICH incidence rate with VKAs). The database was retrospectively queried for patients with AF who were prescribed a DOAC or VKA and had a history of bioprosthetic heart valve replacement. FindingsA total of 434 patients with AF (DOACs, n = 211; VKAs, n = 223) were identified. Propensity score matching identified 130 patients prescribed DOACs (apixaban, 55.4%; rivaroxaban, 30.0%; dabigatran, 13.1%; edoxaban, 1.4%) and the same number of VKA recipients (warfarin, 89.2%; acenocoumarol, 10.8%). The mean (SD) duration of follow-up was 26.8 (2.3) months. The incidence rates of thromboembolic events were 1.3 per 100 person-years in the DOAC group versus 2.0 per 100 person-years in the VKA group (P = 0.14). The incidence rates of major bleed events were 2.6 per 100 person-years in the DOAC group versus 4.9 per 100 person-years in the VKA group (P = 0.47). The incidence rates of ICH were 0.38 per 100 person-years in the DOAC group versus 1.16 in the VKA group (hazard ratio = 0.33; 95% CI, 0.05–2.34; P = 0.3). A positive NCB of DOACs over VKAs of +1.87 was found. ImplicationsAccording to these data from clinical practice, DOACs seem to be associated with a greater NCB versus VKAs in patients with AF with a bioprosthetic heart valve, primarily due to lower rates of both major bleeds and thromboembolic events.

Low-Dose Rivaroxaban and Risks of Adverse Events in Patients With Atrial Fibrillation.

Background and Purpose- In the daily practice, low-dose nonvitamin K antagonist oral anticoagulants are commonly used among Asian patients with atrial fibrillation (AF). The aim of the present study was to compare the risks of ischemic stroke, intracranial hemorrhage, and net clinical benefit of Asian patients with AF treated with off-label low-dose and on-label dosing rivaroxaban. Methods- A total of 2214 patients with AF aged ≥20 years treated with rivaroxaban at a tertiary medical center in Taiwan were studied. Patients were categorized into 2 groups: (1) on-label dose (n=1630): ROCKET-AF or J-ROCKET dosage criteria; and (2) off-label low-dose (10 mg/d for patients with an estimated glomerulus filtration rate >50 mL/min, n=584). The risks of ischemic stroke and intracranial hemorrhage were compared between 2 groups. Results- Compared with the on-label dose group, off-label low-dose rivaroxaban was associated with an increased risk of ischemic stroke with an adjusted hazard ratio of 2.75; 95% CI =1.62-4.69; P<0.001). The risk intracranial hemorrhage did not differ significantly between the on-label and off-label low-dosing groups (adjusted hazard ratio =0.62; 95% CI =0.32-1.20; P=0.213). Compared with off-label low-dose group, on-label dosing rivaroxaban was associated with a positive net clinical benefit in different weighted models. The results were consistent among the propensity-matched cohort. Conclusions- Off-label low-dosing rivaroxaban should be avoided for Asian patients with AF giving the higher risk of ischemic stroke without risk reduction in intracranial hemorrhage compared with on-label dosing.