Multiple thromboses, including intracardiac thrombi, accompanied by HIT during ECMO successfully treated with NOACs: A case report.

INTRODUCTION: Unfractionated heparin remains the mainstay of anticoagulation therapy during extracorporeal membrane oxygenation (ECMO) maintenance. However, its continued use in clinical practice exposes patients to the risk of developing heparin-induced thrombocytopenia (HIT). CASE REPORT: A 50-year-old male was diagnosed with multiple thromboses, including an intracardiac thrombi, accompanied by HIT during ECMO after cardiogenic shock related to acute myocardial infarction. The patient was successfully treated with new oral anticoagulants (NOAC), without significant complications. DISCUSSION: HIT during ECMO resulting in multiple thromboses is rare. To our knowledge, this is the first reported case of NOAC use in this context. CONCLUSION: Although thrombocytopenia and thrombosis can occur for various reasons during ECMO maintenance, it is important to consider HIT as a potential cause. NOACs can be considered as a therapeutic option.

Effect of direct oral anticoagulants on bleeding during and after cataract surgery.

PURPOSE: To assess the risk for intraoperative and postoperative ocular bleeding associated with direct oral anticoagulant treatment in patients undergoing phacoemulsification surgery. METHODS: Consecutive patients had phacoemulsification and intraocular lens implantation while taking uninterrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban). Gender and age-matched patients without antithrombotic therapy were used as the control group. Patients were examined one week postoperatively. Intraoperative and postoperative hemorrhagic and non-hemorrhagic complications were assessed. RESULTS: Forty patients (56 eyes) on direct oral anticoagulants and 120 patients (172 eyes) without anticoagulation, at a mean age of 77 years, had phacoemulsification. There was no significant difference between the groups in the rate of intraoperative and postoperative bleeding. One eye (1.8%) in the treatment group and 3 eyes (1.7%) in the control group had hyphema (p = 0.72). No patient had thromboembolic event during or after surgery. CONCLUSIONS: Cataract surgery was safely performed while continuing direct oral anticoagulation.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study.

AIMS: Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years. METHODS AND RESULTS: The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P < 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790-0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756-0.953, P < 0.001). CONCLUSIONS: The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.

Non-VKA Oral Anticoagulants in Adult Congenital Heart Disease: a Single-Center Study.

PURPOSE: Non-VKA oral anticoagulants (NOACs) prescription is increasing in adults with congenital heart disease (ACHD). However, data on efficacy and safety in ACHD is unclear, particularly in severe CHD. The study aimed to review the safety and efficacy of NOACs in ACHD. METHODS: Retrospective evaluation of ACHD patients started on NOACs from 2014 to 2020, with the primary endpoints of bleeding or thromboembolic events (TE). CHA2DS2-VASc and HAS-BLED scores were calculated, mortality was assessed, and risk factors for bleeding were identified. RESULTS: A total of 93 patients were included, the mean age was 52 ± 15 years, 58% were female, 55.9% had moderate CHD, and 23.7% had severe CHD (3.2% Fontan). Most (66%) had a CHA2DS2-VASc score ≥ 2 and 82% HAS-BLED ≤ 2. In a median follow-up of 41 (IQR 21) months (400.4 patient-years), there were TE in two patients. The annual risk for TE was 0.49%/patient/year. The cardiovascular mortality was 2% and all-cause mortality 5%; there were no fatal TE or bleeding events. Minor (n = 6, 6.5%) and major (n = 3, 3.2%) bleeding events were observed, a median of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. Renal disease (HR 14.6 [95% CI 1.23-73.6], p = 0.033) and the HAS-BLED score were predictors of major (adjusted HR 6.97 [95% CI 1.69-28.78], p = 0.007) and minor (adjusted HR 3.80 [95% CI 1.48-9.78], p = 0.006) bleeding complications. CONCLUSION: In this real-life cohort of selected ACHD, the use of NOACs was safe and effective, with a low incidence of bleeding events.

Efficacy and safety outcomes of patients with atrial fibrillation compared between warfarin and non-vitamin K antagonist oral anticoagulants based on SAMe-TT2R2 score.

OBJECTIVES: This study aimed to investigate the efficacy and safety outcomes of patients with atrial fibrillation (AF) compared between those taking warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) based on SAMe-TT2R2 score. METHODS: AF patients using warfarin or NOACs were enrolled from Thailand's COOL-AF registry. A low SAMe-TT2R2 score was defined as a score of 0-2. The efficacy outcomes were all-cause death, ischemic stroke (IS), transient ischemic attack (TIA), and/or systemic embolization (SE). The safety outcome was major bleeding (MB). The secondary outcome was a combination of cardiovascular (CV) death, IS/TIA/SE, or MB. Cox proportional hazards model was used to compare the event rate between the AF patients taking warfarin and NOACs according to SAMe-TT2R2 score. RESULTS: A total of 2568 AF patients taking oral anticoagulants were enrolled. Warfarin and NOACs were used in 2340 (91.1%) and 228 (8.9%) patients, respectively. Among overall patients, 305 patients taking warfarin (13.0%) and 21 patients taking NOACs (9.2%) had the efficacy outcome, while 155 patients taking warfarin (6.6%) and 11 patients taking NOACs (4.8%) had the safety outcome. After adjustment for confounders, overall patients taking warfarin had significantly more secondary outcome than those taking NOACs (11.4% vs. 7.5%, respectively; adjusted hazard ratio: 1.74, 95% confidence interval: 1.01-2.99; p = 0.045) regardless of SAMe-TT2R2 score. CONCLUSIONS: AF patients taking warfarin had a significantly higher CV death or IS/TIA/SE or MB compared to those taking NOACs regardless of SAMe-TT2R2 score. The results of this study do not support the use of SAMe-TT2R2 score to guide OAC selection.

Potential effects of anticoagulants in preclinical mice models of oral cancer: A systematic review.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. There is mounting evidence to suggest that several components of the coagulation system directly affect carcinogenesis. Our recent in vitro studies demonstrated, for the first time, that various anticoagulants have anticancer effects on OSCC. They also showed the need for the immediate translation of these experimental conditions from bench to preclinical animal models. Here, we carried out a systematic review to summarise existing evidence on murine models built around the interactions between anticoagulants and oral cancer. Only one preclinical murine study was included in our systematic review, investigating the role of heparins in tumour pathophysiology. The paucity of evidence regarding the interactions between oral squamous cell carcinoma and anticoagulants emphasises the urgency with which further preclinical research should be conducted.

Changing trends and factors influencing anticoagulant use in patients with acute ischemic stroke and NVAF at discharge in the NOACs era.

OBJECTIVES: We sought to explore the trends and influencing factors of the use of anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) at discharge in the era of novel oral anticoagulants (NOACs). METHODS: We recruited consecutive inpatients with acute ischemic stroke and NVAF in a registered study (NCT04080830) from January 2016 to December 2021. The relevant data of patients were collected. We compared the proportions of anticoagulant treatment at discharge before and after NOACs entered China's medical insurance system. The proportion of each antithrombotic status as well as anticoagulant agents at discharge in every year were calculated, and the trends during the study period were analyzed. The relevant factors affecting anticoagulant use at discharge were further analyzed. RESULTS: The proportion of anticoagulation at discharge increased significantly after NOACs entered China's medical insurance system in 2018 versus before (χ2 = 42.828, P < 0.001). There were statistically significant differences in antithrombotic status (χ2 = 69.954, P < 0.001) and in the proportion of different anticoagulant drugs (χ2 = 63.049, P<0.001) by year. Anticoagulant therapy (χ2 = 1.55, P = 0.671) and NOACs (χ2 = .178, P = 0.243) increased over 2016-2018 but was relatively stable during 2018-2021. Multivariate logistic regression analysis showed that age ≥75 years, coexisting cerebral artery stenosis, massive cerebral infarction and hemorrhagic transformation were independent risk factors affecting anticoagulants use (all P < 0.05). CONCLUSION: NOACs have indeed improved anticoagulants use in patients with acute ischemic stroke and NVAF at discharge. However, some specific factors affect anticoagulation therapy use at discharge and hinder further improvement even in the NOACs era.

Efficacy and safety of novel oral anticoagulants in patients with atrial nonvalvular atrial fibrillation and diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the effectiveness and safety of new direct oral anticoagulants (NOACs) and warfarin among nonvalvular atrial fibrillation patients with diabetes. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched. Five retrospective cohort studies and four subgroup analyses of RCTs were included in this meta-analysis. RESULTS: A meta-analysis of the data of 26,7272 patients showed that for patients with nonvalvular atrial fibrillation and diabetes, NOACs can significantly reduce the incidence of stroke/systemic embolism (SSE), ischaemic stroke, and haemorrhagic stroke compared with warfarin, with no significant difference in major bleeding and all-cause mortality. Additionally, NOACs were superior to warfarin in the incidence of intracranial bleeding, gastrointestinal bleeding, myocardial infarction, and vascular death. CONCLUSIONS: Among nonvalvular atrial fibrillation patients with diabetes, NOACs were associated with a lower risk of SSE versus warfarin, with no significant difference in major bleeding. Therefore, NOACs may be a better clinical choice.

Impact of malignancy on outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EURObservational research programme in atrial fibrillation general long-term registry.

BACKGROUND: The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management. PURPOSE: To evaluate the outcomes of patients with active or prior malignancy in a contemporary cohort of European AF patients. METHODS: Patients enrolled in the EURObservational Research Programme in AF General Long-Term Registry were categorized into 3 categories: No Malignancy (NoMal), Prior Malignancy (PriorMal) and Active Malignancy (ActiveMal). The primary outcomes were all-cause death and the composite outcome MACE. RESULTS: A total of 10 383 patients were analysed. Of these, 9597 (92.4%) were NoMal patients, 577 (5.6%) PriorMal and 209 (2%) ActiveMal. Lack of any antithrombotic treatment was more prevalent in ActiveMal patients (12.4%) as compared to other groups (5.0% vs 6.3% for PriorMal and NoMal, p < .001). After a median follow-up of 730 days, there were 982 (9.5%) deaths and 950 (9.7%) MACE events. ActiveMal was independently associated with a higher risk for all-cause death (HR 2.90, 95% CI 2.23-3.76) and MACE (HR 1.54, 95% CI 1.03-2.31), as well as any haemorrhagic events and major bleeding (OR 2.42, 95% CI 1.49-3.91 and OR 4.18, 95% CI 2.49-7.01, respectively). Use of oral anticoagulants was not significantly associated with a higher risk for all-cause death or bleeding in ActiveMal patients. CONCLUSIONS: In a large contemporary cohort of AF patients, active malignancy was independently associated with all-cause death, MACE and haemorrhagic events. Use of anticoagulants was not associated with a higher risk of all-cause death in patients with active malignancies.

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients.

PURPOSE: The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. METHODS: This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. RESULTS: Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

Non-vitamin K antagonist oral anticoagulants in venous thromboembolism patients: a meta-analysis of real-world studies.

BACKGROUND: The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings. METHODS: Search of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events. RESULTS: Adjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71-1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09-1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15-2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome. CONCLUSIONS: In the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice. TRIAL REGISTRATION: This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).

Gastrointestinal Bleeding Due to NOACs Use: Exploring the Molecular Mechanisms.

Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed®, UpToDate®, Web of Science®, and Cochrane® about NOACs' risks and benefits in patients requiring anticoagulation, with a focus on gastrointestinal bleeding and on molecular and pathophysiological mechanisms underlying the risk of bleeding in patients treated with them. Apixaban resulted in a lower rate of gastrointestinal bleeding compared to dabigatran and rivaroxaban. However, data reported that gastrointestinal bleeding in patients treated with NOACs was less severe compared to warfarin. Studies show promising results on the increased and widespread use of NOACs in patients who require anticoagulation (for example-in case of atrial fibrillation or high risk of venous thromboembolism), reporting an overall lower risk of major bleeding events. The profile of NOACs was more effective and secure compared to warfarin, but a more careful medical prescription is required in patients who are at high risk of gastrointestinal bleeding.

Dabigatran-Induced Nephropathy and Gastrointestinal Bleeding and Its Successful Treatment with Idarucizumab: A Case Report.

Recently, the atrial fibrillation treatment guidelines have been updated to now recommend Non-vitamin K antagonist oral anticoagulants (NOACs) as the preferred alternative to warfarin for systemic embolism and stroke prevention in patients with non-valvular atrial fibrillation. NOACs have major pharmacologic advantages over warfarin, although the most common complications are gastrointestinal bleeding and NOAC-induced nephropathy within 6 weeks after starting therapy, as several recent case-reports stated. We are reporting for the first time a chronic delayed adverse reaction (regularly reported to Authorities) observed in an 82-year-old woman 27 months after starting dabigatran (110 mg twice a day), characterized by concomitant gastrointestinal bleeding and nephropathy. Idarucizumab administration immediately improved both bleeding and renal parameters. Moreover, we are going to highlight the importance of the compliance, the adherence to the therapeutic plan and the supervision of the Hospital Pharmacy on drug prescriptions. In fact in our case, dabigatran was firstly prescribed by the neurologist and delivered by the hospital pharmacy, but the patient continued the treatment for 27 months, prescribed by general practitioner without any laboratory control. This lack of supervision certainly contributed to the onset of the adverse reaction reported.

Bleeding events in the emergency department with warfarin versus novel oral anticoagulants: A five-year analysis.

Background: Although warfarin is the most effective treatment approved to prevent atrial fibrillation-associated stroke, it remains underused in clinical practice due to patient noncompliance. Therefore, novel oral anticoagulants (NOACs) have been developed. Aims: This study aimed to identify bleeding complications in patients who were taking oral anticoagulants and compare the rates of major and minor bleeding events between NOACs and warfarin groups. Patients and Methods: We conducted a retrospective, observational study of warfarin- and NOAC-treated patients who presented to an emergency department between January 2015 and December 2019 with bleeding events. We compared patients with major and minor bleeding in terms of age, gender, comorbid diseases, type of anticoagulant, and site of bleeding. Results: An electronic search yielded 95 (21.9%) cases of patients taking a NOAC (i.e., dabigatran [19], rivaroxaban [45], apixaban [29], or edoxaban [6]) and 354 taking warfarin. There were no significant differences between the warfarin and NOACs groups in the frequency of minor bleeding complications. Similarly, there were no significant differences between the groups in the frequency of major bleeding complications. No significant difference in intracranial bleeding was seen between the NOACs- and warfarin-treated patients, although the incidence of gastrointestinal bleeding was significantly higher in the NOACs (P = 0.102 and P = 0.021, respectively). Conclusion: Our findings indicate that rates of major and minor bleeding complications in patients taking NOACs are similar to those in patients taking warfarin. While warfarin was associated with fewer complications than NOACs in terms of gastrointestinal bleeding, the risk of intracranial bleeding, was similar between the groups.

Non-vitamin K antagonist oral anticoagulants versus warfarin in AF patients ≥ 85 years.

BACKGROUND: Atrial fibrillation (AF) prevalence and its risk of stroke rise with ageing. We aimed to investigate the outcomes of NOAC and warfarin in AF patients aged ≥ 85 years. METHODS: This is a retrospective study using Taiwan National Health Insurance Research Database. A total of 15,361 patients aged ≥ 85 years with AF on oral anticoagulants were identified. The end points included ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite adverse events (ICH or major bleeding or all-cause mortality). Clinical outcomes were compared between each NOAC and warfarin after propensity matching. RESULTS: Before propensity matching, patients taking warfarin were older, more female with more comorbidities than NOACs users. After propensity matching, baseline characteristics did not differ significantly between matched subjects receiving warfarin and each NOAC. Compared to warfarin, dabigatran was associated with a lower risk of ICH (hazard ratio [HR] 0.496), mortality (HR 0.558) and adverse events (HR 0.628), while rivaroxaban was associated with a lower risk of ischaemic stroke (HR 0.781), ICH (HR 0.453), mortality (HR 0.558) and adverse events (HR 0.636). Apixaban was associated with a lower risk of mortality (HR 0.488) and adverse events (HR 0.557) compared to warfarin. (all P < .05). CONCLUSION: For the efficacy, NOACs were associated with a comparable or lower risk of ischaemic stroke compared to warfarin. For adverse events, NOACs were associated with a lower risk of all-cause mortality and composite adverse events. In the elderly AF population, NOACs could be a more favourable choice for stroke prevention.

Comparison of non-vitamin K antagonist oral anticoagulants on bleeding and thrombosis.

WHAT IS KNOWN AND OBJECTIVE: Limited data are available for the comparison between different non-vitamin K antagonist oral anticoagulants (NOACs) on clinical outcomes. We aimed to provide evidence of different NOACs for patients with non-valvular atrial fibrillation (NVAF). METHODS: Electronic databases were searched from inception through 22 March 2020 to identify eligible studies in which clinical outcomes (stroke, systemic embolism [SE], bleeding or death events) were directly compared between different NOACs. RESULTS: 29 real-world studies enrolled more than 700,000 patients were included. Compared with dabigatran, apixaban had higher risk of death (OR 1.07), major bleeding (1.43), GI bleeding (1.64), ischaemic stroke and stroke/SE events (1.10); rivaroxaban had higher risk of death (1.28), major bleeding (1.24), GI bleeding (1.14) and ischaemic stroke (1.08). Compared with rivaroxaban, apixaban had lower risk of death (0.8), major bleeding (0.56) and ischaemic stroke events (0.71). Compared with edoxaban, rivaroxaban had higher risk of major bleeding (2.83), GI bleeding (5.18) and ischaemic stroke (2.28). WHAT IS NEW AND CONCLUSION: In view of the global burden of disease and the routine use of NOACs worldwide, the findings have immediate and important implications. Our data suggested that apixaban might be the priority choice in prevention of bleeding and stroke and dabigatran could be the priority choice in prevention of death events. TRIAL REGISTRATION: This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and was registered with PROSPERO (CRD42019140553).

Current use and safety of novel oral anticoagulants in adults with congenital heart disease: results of a nationwide analysis including more than 44 000 patients.

AIMS: To evaluate the use of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in adult congenital heart disease (ACHD) and assess outcome in a nationwide analysis. METHODS AND RESULTS: Using data from one of Germany's largest Health Insurers, all ACHD patients treated with VKAs or NOACs were identified and changes in prescription patterns were assessed. Furthermore, the association between anticoagulation regimen and complications including mortality was studied. Between 2005 and 2018, the use of oral anticoagulants in ACHD increased from 6.3% to 12.4%. Since NOACs became available their utilization increased constantly, accounting for 45% of prescribed anticoagulants in ACHD in 2018. Adult congenital heart disease patients on NOACs had higher thromboembolic (3.8% vs. 2.8%), MACE (7.8% vs. 6.0%), bleeding rates (11.7% vs. 9.0%), and all-cause mortality (4.0% vs. 2.8%; all P < 0.05) after 1 year of therapy compared with VKAs. After comprehensive adjustment for patient characteristics, NOACs were still associated with increased risk of MACE (hazard rate-HR 1.22; 95% CI 1.09-1.36) and increased all-cause mortality (HR 1.43; 95% CI 1.24-1.65; both P < 0.001), but also bleeding (HR 1.16; 95% CI 1.04-1.29; P = 0.007) during long-term follow-up. CONCLUSION: Despite the lack of prospective studies in ACHD, NOACs are increasingly replacing VKAs and now account for almost half of all oral anticoagulant prescriptions. Particularly, NOACs were associated with excess long-term risk of MACE, and mortality in this nationwide analysis, emphasizing the need for prospective studies before solid recommendations for their use in ACHD can be provided.

Warfarin vs non-vitamin K oral anticoagulants for left atrial appendage thrombus: A meta-analysis.

INTRODUCTION: Novel oral anticoagulants (NOACs) are commonly used for thromboembolic risk reduction and treatment of pulmonary embolism and deep venous thrombosis. However, data regarding their efficacy and safety in comparison to warfarin for left atrial appendage thrombus is limited. METHODS: A comprehensive literature search in PubMed, Google Scholar, and Cochrane Review from inception to 30 October 2019 was performed. Studies reporting clinical outcomes comparing warfarin vs NOACs were included. Two investigators independently extracted the data and individual quality assessment was performed. A meta-analysis was performed using random-effects model to calculate risk ratio (RR) and 95% confidence interval (CI). The analysis was performed using RevMan 5.3. RESULTS: Four studies met inclusion criteria and a total of 322 patients were included of whom 141 were in the NOAC arm and 181 were in the warfarin arm. There was no significant difference in thrombus resolution between the two groups (RR, 1.00; 95% CI [0.77-1.29; P = .98]). There was no significant difference in major bleeding (RR, 1.30; 95% CI [0.14-12.21; P = .82]) or stroke (RR, 0.42; 95% CI [0.09-2.06; P = .29]) between the two groups. CONCLUSION: The results of our meta-analysis show that NOACs are as efficacious and safe as warfarin in the treatment of left atrial appendage thrombus in patients with non-valvular atrial fibrillation.

Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants.

BACKGROUND: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. METHODS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. RESULTS: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. CONCLUSION: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Efficacy and safety outcomes in novel oral anticoagulants versus vitamin-K antagonist on post-TAVI patients: a meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been a favored option for the patient who suffered from symptomatic aortic stenosis. However, the efficacy and safety outcomes in novel oral anticoagulants (NOACs) versus Vitamin-K antagonist (VKA) for post-TAVI patients are still controversial. This meta-analysis aims at comparing the clinical outcome and safety of NOACs and VKA in the patients after receiving TAVI. METHOD: We searched literature articles in all reachable databases, and observational study as well as randomized controlled trial would be included in order to perform a comprehensive analysis. All-cause mortality, major or life-threatening bleeding, disabling or nondisabling stroke were main pooled outcome measures. Subgroup analysis and meta-regression were adopted to explore heterogeneity. Assessment of bias was performed under the suggestion of Cochrane's Collaboration Tool. RESULTS: We collected 3841 non-duplicate citations from PubMed, Embase, Cochrane and ClinicalTrials.gov, and eventually 7 studies were included for this meta-analysis. As a result, VKA showed priority against NOACs in the field of anti-thromboembolism (4435 participants, RR:1.44, 95% CI: 1.05 to 1.99, I2 = 0%, P = 0.02). CONCLUSION: With corroborative analysis of severe complications, VKA is shown to be more protective on post-TAVI patients in disabling or nondisabling stroke scenario but not in mortality or bleeding event.