Efficacy In Stroke Prevention Research Articles

Clinical outcome in hypertensive patients treated with amlodipine plus bisoprolol or plus valsartan

Clinical outcome in hypertensive patients treated with amlodipine plus bisoprolol or plus valsartan

Current Gaps in the Provision of Safe and Effective Anticoagulation in Atrial Fibrillation and the Potential for Factor XI-Directed Therapeutics.

The global prevalence of atrial fibrillation is rapidly increasing, in large part due to the aging of the population. Atrial fibrillation is known to increase the risk of thromboembolic stroke by 5 times, but it has been evident for decades that well-managed anticoagulation therapy can greatly attenuate this risk. Despite advances in pharmacology (such as the shift from vitamin K antagonists to direct oral anticoagulants) that have increased the safety and convenience of chronic oral anticoagulation in atrial fibrillation, a preponderance of recent observational data indicates that protection from stroke is poorly achieved on a population basis. This outcomes deficit is multifactorial in origin, stemming from a combination of underprescribing of anticoagulants (often as a result of bleeding concerns by prescribers), limitations of the drugs themselves (drug-drug interactions, bioaccumulation in renal insufficiency, short half-lives that result in lapses in therapeutic effect, etc), and suboptimal patient adherence that results from lack of understanding/education, polypharmacy, fear of bleeding, forgetfulness, and socioeconomic barriers, among other obstacles. Often this adherence is not reported to treating clinicians, further subverting efforts to optimize care. A multidisciplinary, interprofessional panel of clinicians met during the 2023 International Society of Thrombosis and Haemostasis Congress to discuss these gaps in therapy, how they can be more readily recognized, and the potential for factor XI-directed anticoagulants to improve the safety and efficacy of stroke prevention. A full appreciation of this potential requires a reevaluation of traditional teaching about the "coagulation cascade" and decoupling the processes that result in (physiologic) hemostasis and (pathologic) thrombosis. The panel discussion is summarized and presented here.

Effect of plateletcrit and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on folic acid efficacy in stroke prevention

Previous studies have shown that low platelet count combined with high plasma total homocysteine (tHcy) increased stroke risk and can be lowered by 73% with folic acid. However, the combined role of other platelet activation parameters and the methylenetetrahydrofolate reductase (MTHFR) C677T genotypes on stroke risk and folic acid treatment benefit remain to be examined. This study aimed to investigate if platelet activation parameters and MTHFR genotypes jointly impact folic acid treatment efficacy in first stroke prevention. Data were derived from the China Stroke Primary Prevention Trial. This study includes a total of 11,185 adult hypertensive patients with relevant platelet activation parameters and MTHFR genotype data. When simultaneously considering both platelet activation parameters (plateletcrit, platelet count, mean platelet volume, platelet distribution width) and MTHFR genotypes, patients with both low plateletcrit (Q1) and the TT genotype had the highest stroke incidence rate (5.6%) in the enalapril group. This subgroup significantly benefited from folic acid treatment, with a 66% reduction in first stroke (HR: 0.34; 95% CI: 0.14–0.82; p = 0.016). Consistently, the subgroup with low plateletcrit (Q1) and the CC/CT genotype also benefited from folic acid treatment (HR: 0.40; 95% CI: 0.23–0.70; p = 0.001). In Chinese hypertensive adults, low plateletcrit can identify those who may greatly benefit from folic acid treatment, in particular, those with the TT genotype, a subpopulation known to have the highest stroke risk.

Should left atrial appendage closure be considered in resistant left atrial appendage thrombus cases? 'Former Foe, New Ally'.

The study explores left atrial appendage closure (LAAC) as a safe and effective alternative to anticoagulation for atrial fibrillation (AF) patients at high bleeding risk. Complications, such as cardioembolic events due to left atrial appendage thrombus (LAAT), highlight the need for alternative stroke prevention strategies. This research assesses LAAC's safety and efficacy in patients with LAAT, aiming to offer valuable insights into its potential as a viable option for stroke prevention in such cases. The study included 205 patients who underwent LAAC using specific devices between September 2015 and February 2023. Among them, 32 patients had persistent LAAT. Baseline characteristics, antithrombotic medications, risk scores, and LAAC indications were documented. Patients were followed to monitor significant clinical events like stroke, cardiovascular mortality, and all-cause mortality. The mean age was 71.9 and mostly female. Indications for LAAC were ischemic cerebrovascular events (CVE) despite anticoagulation (25%), bleeding complications (major/minor, 37.5% each), or both. Successful LAA closure was achieved in all cases, with minimal pericardial effusion in one. One-month follow-up showed no major events or device-related issues. Median follow-up of 16.5 months saw 21.9% non-cardiac deaths. The study underscores LAAC's efficacy for stroke prevention in patients with persistent LAAT. The LAAC in cases of LAAT, whether pursued initially or as a deferred approach, demonstrates feasibility and safety, exhibiting notable procedural success and minimal incidence of periprocedural complications.

Minimally invasive left atrial appendage occlusion plus reduced dose direct oral anticoagulant to prevent stroke in patients with atrial fibrillation-the LAAO-PlusRE.

The onset of atrial fibrillation (AF) has a direct association with left atrial appendage (LAA) function, as demonstrated by recent studies demonstrating the link between left atrial (LA) wall fibrosis, impaired contractility, and the development of AF. Non-valvular AF (NVAF) affects almost 30 million people worldwide, with this number expected to increase in the next 20 years. It is the main cause of ischemic stroke, with significant subsequent economic and social impact. Currently, the mainstay of stroke prevention in patients with NVAF is oral anticoagulation (OAC), which reduces the incidence of ischemic events at the stake of increased hemorrhagic events. Despite the introduction and widespread use of direct oral anticoagulants (DOACs), which almost completely replaced vitamin K antagonists (VKAs), the adherence to OAC is still low, hindering the efficacy of stroke prevention. Percutaneous LAA occlusion (LAAO) is now indicated (class IIB) in patients with NVAF at increased ischemic risk who cannot undergo OAC. Recently published data demonstrated that a reduced dose of DOAC after percutaneous LAAO is superior to long-term dual antiplatelet therapy (DAPT) for stroke prevention in the mid-term. One of the possible pitfalls of percutaneous LAAO is postprocedural peri-device leaks (PDLs) that have been associated with increased thromboembolic events. According to LAAOS III results, surgical LAAO during cardiac surgery brings a 33% reduction in risk of stroke at five years, independently from the OAC regimen with a high rate of complete appendage occlusion. The combination of surgical LAAO and reduced dose DOAC might ensure adequate embolic prevention, lowering the hemorrhagic risk. The present manuscript aims to describe the rationale and design of the Minimally Invasive Left Atrial Appendage Occlusion Plus REduced Dose DOAC To Prevent Stroke In Patients With Atrial Fibrillation Randomized Clinical Trial (LAAO-PlusRE).

Milvexian: A Focus on a New Oral Anticoagulant that Targets Factor XIa for Thromboembolism Prophylaxis.

Drugs that target factor XI and/or XIa have been evaluated as alternatives to existing anticoagulants, in light of studies that indicate that a decrease in Factor XI/XIa levels or activity may result in a lower risk of thrombosis without a significant increase in bleeding risk. Milvexian is an investigational small-molecule factor XIa inhibitor that has recently completed phase 2 clinical trials. Preclinical studies were suggestive of its potential to prevent arterial and venous thrombosis. It was well-tolerated in healthy participants, as well as in participants with mild or moderate hepatic impairment and moderate or severe renal impairment. Notably, patients who received milvexian after knee arthroplasty had a dose-proportional lower incidence of venous thromboembolism compared to patients who received postoperative enoxaparin, and they had a lower incidence of clinically relevant bleeding. A separate phase 2 trial was conducted that assessed the use of milvexian for secondary stroke prevention in patients who had ischemic stroke or transient ischemic attack. It failed its primary objective of establishing a dose-response relationship between milvexian and a composite endpoint of symptomatic ischemic stroke or covert brain infarction. The trial did, however, show a reduction in the relative risk of symptomatic ischemic stroke across most of the treatment groups receiving various dosages of milvexian compared to placebo. The efficacy of milvexian in secondary stroke prevention will be further assessed in an upcoming phase 3 trial. Additional upcoming phase 3 trials will also assess its efficacy in stroke prevention in patients with atrial fibrillation as well as in event reduction in patients with acute coronary syndrome.

From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR:.85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Managing thrombotic complications in heart failure: role of warfarin and other anticoagulants

This article summarizes the findings of research aimed at comparing the effectiveness of anticoagulants in patients with atrial fibrillation and concomitant conditions, including heart failure. The studies evaluated the impact of warfarin, aspirin, dabigatran, edoxaban, and rivaroxaban on the risk of stroke, systemic embolisms, and bleeding events. The results indicate significant differences in the efficacy and safety of these medications: warfarin reduces the risk of stroke but increases the likelihood of bleeding; edoxaban and rivaroxaban showed a decrease in bleeding risk while maintaining efficacy in stroke prevention. The research also identified the stability of drug effects based on the severity of heart failure, emphasizing the need for an individualized approach to treatment selection in this patient group.

Lower rate of major bleeding in very high risk patients undergoing left atrial appendage occlusion: A propensity score–matched comparison with direct oral anticoagulant

BackgroundLong-term oral anticoagulation is the mainstay therapy for thromboembolic (TE) prevention in patients with atrial fibrillation. However, left atrial appendage occlusion (LAAO) could be a safe alternative to direct oral anticoagulants (DOACs) in patients with a very high TE risk profile. ObjectiveThe purpose of this study was to compare the safety and efficacy of LAAO vs DOACs in patients with atrial fibrillation at very high stroke risk (CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category] score ≥ 5). MethodsData from patients with CHA2DS2-VASc score ≥ 5 were extracted from a prospective multicenter database. To attenuate the imbalance in covariates between groups, propensity score matching was used (covariates: CHA2DS2-VASc and HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] scores), which resulted in a matched population of 277 patients per group. The primary end point was a composite of cardiovascular death, TE events, and clinically relevant bleeding during follow-up. ResultsOf 2381 patients, 554 very high risk patients were included in the study (mean age 79 ± 7 years; CHA2DS2-VASc score 5.8 ± 0.9; HAS-BLED score 3.0 ± 0.9). The mean follow-up duration was 25 ± 11 months. A higher incidence of the composite end point was documented with DOACs compared with LAAO (14.9 events per 100 patient-years in the DOAC group vs 9.4 events per 100 patient-years in the LAAO group; P = .03). The annualized clinically relevant bleeding risk was higher with DOACs (6.3% vs 3.2%; P = .04), while the risk of TE events was not different between groups (4.1% vs 3.2%; P = .63). ConclusionIn high-risk patients, LAAO had a similar stroke prevention efficacy but a significantly lower risk of clinically relevant bleeding when compared with DOACs. The clinical benefit of LAAO became significant after 18 months of follow-up.

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in Chronic Kidney Disease, Congestive Heart Failure and Stroke-A Review and Clinical Guide for Healthcare Professionals.

Diabetic kidney disease (DKD) causes a progressive decline in renal function, leading to end-stage kidney disease (ESKD), and increases the likelihood of cardiovascular events and mortality. The recent introduction of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor has been a game changer in managing chronic kidney disease (CKD) and congestive heart failure (CHF). These agents not only slow down the progression of kidney disease but also have cardioprotective benefits, including for patients with congestive heart failure and atherosclerotic cardiovascular disease. Some evidence suggests that they can decrease the risk of stroke as well. This review aims to provide a comprehensive overview of the role of SGLT-2 inhibitors in CKD and CHF and their efficacy in stroke prevention. This review includes a comparison with glucagon-like peptide-1 (GLP-1) agonist and finerenone; focuses on safety data, the potential benefits beyond glycemic control, and a review of significant trials; and provides guidance in clinical practice.

Asundexian: an oral small moleculefactor XIa inhibitor for the treatment of thrombotic disorders.

Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding often dictate treatment decisions. Inhibition of the intrinsic coagulation system via factor XIa may allow for selective inhibition of the coagulation cascade without significantly impacting hemostasis after injury. Asundexian is an oral small moleculefactor XIa inhibitor that, via this novel mechanism, may prove to be a safe and effective option compared with available anticoagulants. Early clinical data forasundexian was promising as a safer alternative to current therapiesand prompted further analysis incertainpatient populations atincreasedthrombotic risk. Currently, studies areongoing to evaluate thesafety and efficacy in stroke prevention in atrial fibrillation and in patients following an acute noncardioembolic ischemic stroke or high-risk transient ischemic attack.

Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials.

Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal efficacy in stroke prevention and greater safety in terms of intracranial bleeding. The study population in the randomized trials of DOACs was highly selected, so the results of these trials cannot be extended to specific populations such as obese, elderly, frail, and cancer patients, which, on the other hand, are sub-populations widely represented in clinical practice. Furthermore, due to the negative results of DOAC administration in patients with mechanical heart valves, the available evidence in subjects with biological heart valves is still few and often controversial. We sought to review the available literature on the efficacy and safety of DOACs in elderly, obese, underweight, frail, cancer patients, and in patients with bioprosthetic heart valves with NVAF to clarify the best anticoagulant strategy in these special and poorly studied subpopulations.

Percutaneous Left Atrial Appendage Closure With a Novel LAA Occluder for Stroke Prevention in Atrial Fibrillation.

More than 90% of thromboses originate from the left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation (NVAF). This study was designed to investigate the safety and efficacy of LAA closure with the Leftear device (Pulse Scientific) in NVAF patients. A prospective, multicenter, registry-based study was conducted in 200 NVAF patients with CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack, vascular disease, female sex) scores≥2. The primary safety endpoint was defined as any serious adverse events. Efficacy was assessed by a primary composite endpoint of hemorrhagic or ischemic stroke, systemic embolism, and cardiac or unexplained death at 1 year of follow-up. The device was implanted in 196 patients, with 1-stop LAA closure combined with atrial fibrillation ablation implemented in 133 patients. The immediate success rate was 100%. There were serious adverse events in 9 patients (4.5%; 95%CI: 1.6%-7.4%), which mainly occurred in 1-stop LAA closure. All pericardial tamponades occurred in 6patientswith 1-stop LAA closure. No patient experienced a major bleeding event or acute device-related thrombus. During the 12-month follow-up period, the risk of the primary composite endpoint was 1.6% (95%CI: 0.3%-4.5%), and statistical noninferiority was achieved (the upper bound of 95%CI: 4.5%< the prespecified maximum annual incidence of 8.0%). Ischemic stroke occurred in 1 patient, 3 patients had incomplete LAA sealing, and no delayed device-related thrombus was found. LAA closure with the novel disc-like occluder shows high procedural success, satisfactory safety, andencouraging efficacy for stroke prevention in patients with NVAF. Compared with 1-stop LAA closure, single LAAclosure may be more tolerable. (A multicenter, single-arm clinical trial to evaluate the efficacy and safety of left atrial appendage system for left atrial appendage occlusion in patients with non-valvular atrial fibrillation; ChiCTR1900023035).

Clinical outcomes associated with left atrial appendage occlusion via implanted device in atrial fibrillation:a Nationwide Matched Control Study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction / Background Left atrial appendage occlusion (LAAO) has emerged as a nonpharmacological alternative for stroke prevention in patients with atrial fibrillation (AF). Contemporary data regarding the characteristics and outcomes of patients undergoing this procedure compared to a control group not treated with LAAO are limited. Purpose Our objective was to compare outcomes following first LAAO implantation in an exhaustive nationwide matched cohort. Methods This French longitudinal cohort study was based on the national hospitalization database covering hospital care from for the entire population. All adults (age ≥18 years) hospitalized in French hospitals with AF from January 1, 2015 to January 1, 2020, who underwent a LAAO implantation were identified. Owing to the non-randomized nature of the study, and considering for significant differences in baseline characteristics between AF patients treated with LAAO and no LAAO, propensity-score matching was used to control for potential confounders of the treatment outcome relationship. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3) or all-cause mortality during follow-up. Results After propensity score matching 2,682 patients with LAAO were matched 1:1 with 2,682 AF patients not treated with LAAO. Baseline characteristics of matched patients are illustrated in Figure 1. Mean follow-up was 7 months (median 5, interquartile 1-11 months). As illustrated in Figure 2, AF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients not treated with LAAO (hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.52 to 0.68). Total events and event rates per 100 patient-years were (LAAO vs. no LAAO) 315 vs. 591 and 20.6%/year vs. 36.1%/year, respectively. The risk of ischemic stroke was comparable between groups (HR 1.06, 95% CI: 0.75 to 1.17), while risk of major bleeding (HR 0.49, 95% CI: 0.37 to 0.65) and all-cause mortality (HR 0.57, 95% CI: 0.48 to 0.67) were significantly lower in patients treated with LAAO. Conclusion Among AF patients with a high risk of bleeding, our nationwide study highlighted a high risk of clinical events during follow-up. Patients treated with LAAO may have similar stroke prevention efficacy but lower risk of major bleeding and mortality when compared to propensity score-matched patients not treated with LAAO.

Cost-effectiveness of apixaban versus other oral anticoagulants and aspirin for stroke prevention in atrial fibrillation in indian subcontinent

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer Ltd Background/Introduction Non-vitamin K antagonist oral anticoagulants (NOACs) are class I recommended by various guidelines for stroke prevention in atrial fibrillation. NOACs are associated with comparable or lower risk of stroke / systemic embolism and significantly lower major bleeding as compared to VKAs. Despite the fact that NOACs have demonstrated safety and efficacy in stroke prevention in AF by various randomized clinical trials and real-world evidences, the pharmacoeconomic data of NOACs in stroke prevention is lacking in India. In view of the higher initial and long-term cost of the NOAC therapy, it is important to analyze the cost effectiveness of such therapy to ensure wider acceptance and compliance to medication since majority of population in India is self-paying. Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban versus other NOACs available in India (dabigatran and rivaroxaban), warfarin and aspirin for stroke prevention in atrial fibrillation from the healthcare providers’ and patients’ perspectives in the government healthcare as well as the private healthcare facilities across Indian subcontinent. Methods A Markov model was constructed using six-week cycle length over a lifetime horizon by including the available data from RCTs and real-world analyses of all NOACs. The clinical consequences of AF included in the analysis were stroke (ischemic and hemorrhagic), systemic embolism, bleeding (intracranial hemorrhage, other major and clinically relevant non-major), myocardial infarction, mortality and morbidity associated with NVAF not on anticoagulant. Innovator brands of NOACs were considered for this analysis, as NOACs are not under price control in India unlike warfarin and aspirin. Model outputs included quality-adjusted life years (QALY), life years gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). Additional sensitivity and scenario analyses were conducted to test the robustness of the outcomes. Results From healthcare provider’s perspective irrespective of private medical facility or the government healthcare facilities, Apixaban was dominantly associated with cost-saving over other OACs. Apixaban was cost effective as compared to warfarin from patients’ perspective at the private medical facilities. Apixaban was cost-effective compared to dabigatran and rivaroxaban from patients’ perspective in the RWE-based analysis. Conclusion We conclude that apixaban is cost saving (less costly and more effective) compared to warfarin, aspirin and other NOACs from healthcare providers’ perspective. Apixaban may be a cost-effective alternative to dabigatran and rivaroxaban from patients’ perspective as per the RWD-based cost-effectiveness analysis. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare professionals and decision-makers. Abstract Figure. Incremental cost-effectiveness ratios

Carotid endarterectomy in asymptomatic octogenarians: Outcomes at 30 days and 5 years.

The following study investigated the 30-day and 5-year relative survival rate and freedom from neurological events in asymptomatic carotid stenosis (ACS) octogenarians who had undergone elective carotid endarterectomy (CEA). Between January 2008 and June 2014, a retrospective review was conducted on ACS patients who had undergone elective CEA. The patients' sample was divided into two groups: Group A (GA) included octogenarians and Group B (GB) included younger patients. The GA patients were subjected to a risk-scoring system and follow-up. The two groups were compared analysing the following primary endpoints: 30-day mortality, stroke, stroke/death and acute myocardial infarction (AMI); GA patients' survival rate and freedom from neurological events at 5years. The 30-day secondary endpoints included carotid shunting, redo surgical, need for general anaesthesia with preserved consciousness (GAPC) conversion and length of hospital stay. We identified 620 patients with ACS, of them 144 (23.2%) belonged to the GA and 476 (76.8%) belonged to the GB. No statistical difference between the two groups was found regarding the primary and secondary endpoints. One hundred nineteen of 144GA patients (82.6%) underwent the follow-up; the median follow-up was 78.3months. The GA patients' 5-year survival rate was 62%, while freedom from cerebral events was 94.9%. Analysis regarding GA patients' 5-year survival rate revealed a significantly lower percentage among the patients with a severe risk score compared with those with a moderate risk score (respectively, 29.5% vs 67.7%; p = .005). The multivariate analysis showed that chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were independently associated with lower survival. The 30-day outcomes of CEA in octogenarians are comparable to those in younger patients. Comprehensive life expectancy and preoperative score, rather than age alone, should be taken into account before performing CEA on octogenarian patients, considering the short- and long-term efficacy in stroke prevention.

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.

Direct oral anticoagulants versus vitamin K antagonists for patients with left ventricular thrombus: a systematic review and meta-analysis.

Although vitamin K antagonists (VKAs) are recommended as first-line anticoagulants for patients with left ventricular thrombus (LVT), accumulating evidence suggests direct oral anticoagulants (DOACs) could be safe alternatives for VKAs. Efficacy and safety of DOACs should be assessed to justify their usage for LVT patients. To compare the efficacy and safety of DOACs and VKAs for the treatment of LVT. We performed a meta-analysis of observational studies to compare DOACs to VKAs in LVT patients. The PubMed and EMBASE databases were searched for articles published until November 12, 2020. Pooled effects were estimated using Mantel-Haenszel method and presented as risk ratios (RR) using fixed-effect model. Reporting followed the Meta-analyses of observational studies in epidemiology (MOOSE) guideline. A total of 2467 LVT patients from 13 studies were included. Compared with VKAs, DOACs showed similar efficacy in prevention of stroke or systemic embolism (RR: 0.96, 95% confidence interval [CI]: 0.80-1.16, P = 0.68) and thrombus resolution (RR: 0.88, 95% CI: 0.72-1.09, P = 0.26), but significantly lower risk of stroke (RR: 0.68, 95% CI: 0.47-1.00, P = 0.048). For safety outcomes, DOAC users showed similar risk of any bleedings (RR: 0.94, 95% CI: 0.67-1.31, P = 0.70), but lower risk of clinically relevant bleedings (RR: 0.35, 95% CI: 0.13-0.92, P = 0.03) compared with VKA users. Compared with VKAs, DOACs acquired similar efficacy and safety profile for patients with LVT, but could reduce the risk of strokes and clinically relevant bleedings.

TCTAP A-059 A Retrospective Case Control Study on Head-to-head Comparison Between LAAO and NOAC in Asian Population: Efficacy of Stroke Prevention and Bleeding Risk

TCTAP A-059 A Retrospective Case Control Study on Head-to-head Comparison Between LAAO and NOAC in Asian Population: Efficacy of Stroke Prevention and Bleeding Risk

Clinical Outcomes Associated With LeftAtrial Appendage Occlusion VersusDirect Oral Anticoagulation in Atrial Fibrillation.

This study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF). LAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF. Patients with AF enrolled in the Amulet Observational Registry (n=1,088) who had successful LAAO with the Amplatzer Amulet device (n=1,078) were compared with a propensity score-matched control cohort of incident AF patients (n=1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA2DS2-VASc (congestive heart failure, hypertension, age≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium≥3), or all-cause mortality, and follow-up was 2 years. AF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95%CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95%CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95%CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO. Among high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.