A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not ...yet been developed.
A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events in these regimens.
A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs exhibited to possess a highly favorable overall profile.
Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrate significantly greater efficacy than aspirin; however, they do not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tend to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies.
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•Thromboembolism is one of the most common complications among Fontan patients•Consensus regarding the thromboprophylaxis strategy has not yet been developed.•A network meta-analysis was conducted to evaluate the comparative effectiveness.•Aspirin showed lower rates of major bleeding.•NOACs are more effective than aspirin, but they do not significantly outperform warfarin.
Hemoglobin levels and platelet counts have been associated with adverse clinical outcomes in patients with cardiovascular conditions. We aimed to assess the impact of oral anticoagulant use for ...patients with atrial fibrillation and concomitant anemia or thrombocytopenia.
We used medical data from a multicenter health care system in Taiwan including 37,074 patients with atrial fibrillation. Patients were categorized into 3 groups based on hemoglobin and platelet levels: Group 1 (hemoglobin >10g/dL and platelet>100 K/µL; n = 29,147), Group 2 (hemoglobin<10 g/dL or platelet<100 K/µL; n = 7078), and Group 3 (hemoglobin <10 g/dL and platelet <100 K/µL; n = 849). Patients in each category were further stratified as 3 groups according to their stroke prevention strategies: no oral anticoagulant use (non-OAC), warfarin, or nonvitamin K antagonist oral anticoagulants (NOACs).
A higher hemoglobin or platelet level was associated with a higher risk of ischemic stroke/systemic embolism but lower risks of intracranial hemorrhage and major bleeding. The composite risks of ischemic stroke/systemic embolism, intracranial hemorrhage and major bleeding were higher in Group 3 or Group 2, compared with Group 1 (6.79% a year vs 6.41% year vs 4.13% year). Compared to non-OACs, warfarin was not associated with a lower composite risk in the 3 groups. NOACs were associated with a lower composite risk in Group 1 (adjusted hazard ratio:0.68, 95% confidence interval:0.60-0.76) and Group 2 (adjusted hazard ratio:0.73, 95% confidence interval:0.53-0.99) but was nonsignificant in Group 3.
Patients with atrial fibrillation with anemia or thrombocytopenia were a high-risk population. Compared with no OAC use, NOACs were associated with better clinical outcomes for patients with atrial fibrillation and advanced anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet <100 K/µL) but not for those with both conditions.
Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging, requiring a balance between thromboembolism prevention and serious bleeding. Comparisons of nonvitamin K ...antagonist oral anticoagulants (NOACs) and warfarin in older adults at different age strata (65-74, 75-89, and ≥ 90 years of age) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared with warfarin for stroke prevention in elderly patients with AF.
From 2012 to 2015, 64,169 patients ≥ 65 years of age with AF who received at least one NOAC (dabigatran, rivaroxaban, or apixaban) or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite adverse events were compared between NOACs and warfarin in all patients ≥ 65 years of age and, specifically, with different age strata (ie, 65-74, 75-89, ≥ 90 years).
Overall, NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio aHR, 0.869; 95% CI, 0.812-0.931), ICH (aHR, 0.524; 95% CI, 0.456-0.601), major bleeding (aHR, 0.824; 95% CI, 0.776-0.875), mortality (aHR, 0.511; 95% CI, 0.491-0.532), and composite adverse events (aHR, 0.646; 95% CI, 0.625-0.667) than warfarin. There was heterogeneity in treatment effect for NOACs vs warfarin in different age strata, but the results still favored NOACs even among very older adults (≥ 90 years). The results were generally consistent with propensity matching analysis. The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among older adults than warfarin.
Compared with warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in very older adults.
The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main ...purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49–0.71) and adverse events (RR: 0.96; 95%CI: 0.93–0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36–0.66), apixaban (RR: 0.54; 95%CI: 0.36–0.81) and edoxaban (RR:0.49; 95%CI: 0.32–0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80–1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33–0.65), advantage events (RR: 0.87; 95%CI: 0.82–0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53–0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.
Abstract
Aims
The stroke risk of patients with atrial fibrillation (AF) is not static, since AF patients get older and accumulate more comorbidities after AF is diagnosed. Therefore, the stroke risk ...of AF patients given certain comorbidities in different age strata should ideally be analysed using an assessment which considers incident comorbidities and the actual age when ischaemic stroke occurred. The goal of the present study is to report the age treatment thresholds for the use of non-vitamin K antagonist oral anticoagulants (NOACs) for AF patients without or with only one comorbidity of the CHA2DS2-VASc score, based on an ‘ideal method’ of stroke risk assessments.
Methods and results
The study cohort included 31 039 and 39 020 AF patients who did not have any or had only one risk factor comorbidity of the CHA2DS2-VASc score except for age and sex. The risks of ischaemic stroke in each age strata for each comorbidities were analysed in three ways, as follows: (i) the conventional way (based on baseline risk factors and age), (ii) dynamic method (patients were censored when new comorbidities occurred), and (iii) an ideal method (patients were censored when new comorbidities occurred and the stroke risk was related to the actual age when stroke happened). The tipping point for the use of NOACs was set at a stroke risk of 0.9%/year. The overall risk of ischaemic stroke using the conventional way was overestimated compared to the dynamic or ideal assessment with the incidence rate ratio of 1.24 for patients with hypertension, 1.20 for heart failure, 1.37 for diabetes mellitus, and 1.38 for vascular diseases; all P-values <0.01. The risk of ischaemic stroke for each age strata was generally higher with the conventional or dynamic methods compared with the ideal assessment. With heart failure, the tipping point (age 35 years) of NOACs was similar, irrespective of methods used for stroke risk assessment. According to the results of ideal assessment, the age thresholds for the use of NOACs for patients with hypertension, diabetes mellitus, and vascular diseases were 50 years, 50 years, and 55 years, respectively.
Conclusion
Ischaemic stroke risk in AF is heterogeneous, depending on different risk factors with age being as an important driver of stroke risk. Age thresholds for the use of NOACs were different for AF patients having different single risk factors beyond sex despite the same CHA2DS2-VASc score point (1 for males and 2 for females); that is, 35 years for heart failure, 50 years for hypertension or diabetes, and 55 years for vascular diseases.
Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, ...significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD).
An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6 months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire).
In total, 530 ACHD patients (mean age 47 SD 15 years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 IQR 0.0–2.0 year, thromboembolic event rate was 1.0% 95%CI 0.4–2.0 (n = 6) per year, with 1.1% 95%CI 0.5–2.2 (n = 7) annualized rate of major bleeding and 6.3% 95%CI 4.5–8.5 (n = 37) annualized rate of minor bleeding. Adherence was sufficient during 2 years follow-up in 80–93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (n = 33), QoL improved in 6 out of 8 domains (p ≪ 0.05).
Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.
•Up until now, no data are available on NOACs in ACHD patients with atrial arrhythmia.•NOACs appear to be safe during short-term use in ACHD with moderate-complex defects.•This may also apply to ACHD patients with valvular disease or bioprosthetic valves.•Future OAC recommendations in ACHD should consider this international experience.
Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next forty years. The advent of ...direct oral anticoagulants (DOACs) has catalyzed significant changes in the therapeutic landscape of VTE treatment. As such, it is imperative that clinicians become familiar with and appropriately implement new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for VTE treatment with the DOACs. When possible, guidance statements are supported by existing published evidence and guidelines. In instances where evidence or guidelines are lacking, guidance statements represent the consensus opinion of all authors of this manuscript and are endorsed by the Board of Directors of the Anticoagulation Forum.
The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings.
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