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Clinical Laboratory Apr 2023Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the... (Review)
Review
BACKGROUND
Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the specialized laboratory, and interpretation of findings together with clinical data, often only part of the necessary laboratory analyses can be performed in remote central laboratories. Restrictive indications for testing, as have been recommended by previous reviews on the topic, have been based on incomplete analytics, studies with small case numbers, or short observation periods, and on an inappropriate, simple risk stratification for venous thromboembolism (VTE), further subdivided into provoked and unprovoked events.
METHODS
The authors reviewed four electronic databases for all peer-reviewed and in-press articles about thrombophilia, VTE, obstetric complications, and arterial thrombosis. After confirmation for relevance to the topic, 201 articles were accepted for inclusion in this article. This review summarizes the studies relevant to the evaluation of thrombophilic conditions, and their combination with each other and with clinical risk factors, to stratify individual risk for thromboembolism and obstetric complications.
RESULTS
Thrombophilia testing requires highly skilled personnel for laboratory analysis and interpretation. Clinical conditions that influence the results as well as special preanalytical, analytical, and postanalytical aspects must be considered if valid results are to be obtained. Tests involved include the natural anticoagulants antithrombin, protein C, and protein S; the procoagulants fibrinogen (dysfibrinogen), prothrombin (mutation G20210A), factor V (Leiden mutation), factor VIII/von Willebrand factor/blood group ABO, factor IX, and factor XI; the anti-phospholipid antibodies to detect an antiphospholipid syndrome and potentially additional uncertain thrombophilic conditions. The risks of thrombophilic conditions and clinical risk factors for VTE are cumulative or even supra-additive. Scores from thrombophilic conditions and other genetic and nongenetic risk factors permit estimation of risk for first and recurrent VTE. Therapeutic strategies can be derived from this risk stratification.
CONCLUSIONS
Thrombophilia testing is indicated when the results have potential to influence the type and duration of treatment. Indications include certain patients after VTE; or patients without previous VTE but with positive family history regarding VTE or thrombophilia before major surgery, pregnancy, combined oral contraceptives, or hormone replacement therapy. Whether or not thrombophilia is present should help determine anticoagulation, hormonal contraception, or hormone replacement.
Topics: Female; Pregnancy; Humans; Venous Thromboembolism; Thrombophilia; Anticoagulants; Risk Factors
PubMed: 37057948
DOI: 10.7754/Clin.Lab.2022.220817 -
Acta Neurologica Scandinavica Jan 2022Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose... (Meta-Analysis)
Meta-Analysis Review
Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose to the risk of venous infarction and hemorrhage. Current guidelines recommend treating CVT with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) followed by an oral vitamin K antagonist (VKA) for 3-12 months. Direct oral anticoagulants (DOACs) have already established benefit over warfarin as a long-term treatment of symptomatic venous thromboembolic disorder like deep vein thrombosis (DVT), and pulmonary embolism (PE) given its equal efficacy and better safety profile. The benefit of DOACs over warfarin as a long-term anticoagulation for CVT has likewise been extensively studied, yet it has not been approved as first-line therapy in the current practice. We therefore performed a systematic review and meta-analysis of relevant studies to generate robust evidence regarding the safety and efficacy of DOACs in CVT. This meta-analysis demonstrates that the use of DOACs in CVT has similar efficacy and safety compared to VKAs with better recanalization rate.
Topics: Administration, Oral; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Venous Thromboembolism; Venous Thrombosis
PubMed: 34287841
DOI: 10.1111/ane.13506 -
A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease.Journal of Nephrology Nov 2022Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in... (Review)
Review
BACKGROUND
Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis.
METHODS
We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included.
RESULTS
Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile.
CONCLUSION
Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.
Topics: Humans; Anticoagulants; Warfarin; Venous Thromboembolism; Administration, Oral; Atrial Fibrillation; Hemorrhage; Renal Insufficiency, Chronic; Heparin, Low-Molecular-Weight
PubMed: 36006608
DOI: 10.1007/s40620-022-01413-x -
American Journal of Kidney Diseases :... Nov 2021To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD).
STUDY DESIGN
Systematic review and pairwise and Bayesian network meta-analysis.
SETTING & STUDY POPULATIONS
Adult patients with AF and CKD stages 3-5D who received OACs.
SELECTION CRITERIA FOR STUDIES
Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR)<60mL/min.
DATA EXTRACTION
Two reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE).
ANALYTICAL APPROACH
Random-effects models using restricted maximum-likelihood methods were fit for the pairwise meta-analyses as well as a network meta-analysis within a Bayesian framework.
RESULTS
Pairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct OACs (DOACs) were superior to warfarin in preventing thromboembolic events (hazard ratio [HR], 0.86 [95% CI, 0.78-0.95]), without heterogeneity (I=10.5%), and in reducing the risk of bleeding events (HR, 0.81 [95% CI, 0.66-0.99]), with substantial heterogeneity (I=69.8%), in patients with AF and a GFR of 15-60mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15-mg dose of edoxaban were superior to the other OAC regimens in reducing bleeding events. Dose-adjusted apixaban was more effective than edoxaban in preventing thromboembolic events for patients with AF and GFR in the range of 25-50 or 30-50mL/min. In dialysis recipients with AF, the use of OACs increased the risk of bleeding events by 28% (HR, 1.28 [95% CI, 1.03-1.60]) without significant beneficial effects versus not using anticoagulants.
LIMITATIONS
Low SOE and heterogeneity in most comparisons.
CONCLUSIONS
This study suggests that DOACs are superior to warfarin for the prevention of thromboembolic events and reduction in bleeding risk in patients with AF and mild to moderate kidney disease. However, the low SOE limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase bleeding risk without significant benefits in dialysis recipients with AF.
REGISTRATION
Registered at PROSPERO with identification number CRD42018090896.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Network Meta-Analysis; Renal Insufficiency, Chronic; Stroke
PubMed: 33872690
DOI: 10.1053/j.ajkd.2021.02.328 -
Pharmacotherapy Apr 2022Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the... (Review)
Review
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.
Topics: Anticoagulants; Drug Interactions; Humans; Platelet Aggregation Inhibitors; Rifabutin; Rifampin; Rifamycins; Warfarin
PubMed: 35152432
DOI: 10.1002/phar.2672 -
JAMA Network Open Nov 2022Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.
OBJECTIVE
To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.
DATA SOURCES
PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.
STUDY SELECTION
The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.
RESULTS
A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.
CONCLUSIONS AND RELEVANCE
In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.
Topics: Male; Adult; Humans; Aged; Adolescent; Female; Hemorrhage; Retrospective Studies; Anticoagulant Reversal Agents; Anticoagulation Reversal; Anticoagulants; Intracranial Hemorrhages; Thromboembolism
PubMed: 36331504
DOI: 10.1001/jamanetworkopen.2022.40145 -
Advances in Therapy Jan 2020International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
International guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists.
METHODS
PubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I statistic.
RESULTS
Of the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88-2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62-1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34-0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32-0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15-1.01]), though significant heterogeneity was observed (I > 60).
CONCLUSION
Literature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare.
FUNDING
Sanofi.
Topics: Anticoagulants; Aspirin; Enoxaparin; Female; Hemorrhage; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Venous Thromboembolism
PubMed: 31673991
DOI: 10.1007/s12325-019-01124-z -
The Cochrane Database of Systematic... Oct 2021Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be... (Review)
Review
BACKGROUND
Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be improved if they are offered anticoagulants that reduce their risk of developing new blood clots and do not increase the risk of bleeding. This is an update of a Cochrane Review first published in 1995, with updates in 2004, 2008, and 2015.
OBJECTIVES
To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) for people with acute presumed or confirmed ischaemic stroke. Our hypotheses were that, compared with a policy of avoiding their use, early anticoagulation would be associated with: • reduced risk of death or dependence in activities of daily living a few months after stroke onset; • reduced risk of early recurrent ischaemic stroke; • increased risk of symptomatic intracranial and extracranial haemorrhage; and • reduced risk of deep vein thrombosis and pulmonary embolism.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (August 2021); the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), in the Cochrane Library (searched 5 August 2021); MEDLINE (2014 to 5 August 2021); and Embase (2014 to 5 August 2021). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.
SELECTION CRITERIA
Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We assessed the overall certainty of the evidence for each outcome using RoB1 and GRADE methods.
MAIN RESULTS
We included 28 trials involving 24,025 participants. Quality of the trials varied considerably. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition, or reporting bias. Anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence is related to effects of anticoagulant therapy initiated within the first 48 hours of onset. No evidence suggests that early anticoagulation reduced the odds of death or dependence at the end of follow-up (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 12 RCTs, 22,428 participants; high-certainty evidence). Similarly, we found no evidence suggesting that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (OR 0.99, 95% CI 0.90 to 1.09; 22 RCTs, 22,602 participants; low-certainty evidence) during the treatment period. Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.75, 95% CI 0.65 to 0.88; 12 RCTs, 21,665 participants; moderate-certainty evidence), it was also associated with an increase in symptomatic intracranial haemorrhage (OR 2.47; 95% CI 1.90 to 3.21; 20 RCTs, 23,221 participants; moderate-certainty evidence). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60, 95% CI 0.44 to 0.81; 14 RCTs, 22,544 participants; high-certainty evidence), but this benefit was offset by an increase in extracranial haemorrhage (OR 2.99, 95% CI 2.24 to 3.99; 18 RCTs, 22,255 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Since the last version of this review, four new relevant studies have been published, and conclusions remain consistent. People who have early anticoagulant therapy after acute ischaemic stroke do not demonstrate any net short- or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis, and pulmonary embolism but increased bleeding risk. Data do not support the routine use of any of the currently available anticoagulants for acute ischaemic stroke.
Topics: Activities of Daily Living; Anticoagulants; Brain Ischemia; Heparin; Humans; Ischemic Stroke; Stroke; Systematic Reviews as Topic
PubMed: 34676532
DOI: 10.1002/14651858.CD000024.pub5 -
Seminars in Thrombosis and Hemostasis Nov 2020Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching...
Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery ( = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients ( = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH ( = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m ( = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m, at standard fixed-dose ( = 20 studies). The limited available evidence on fondaparinux ( = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.
Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Obesity
PubMed: 33368113
DOI: 10.1055/s-0040-1718405 -
Circulation Mar 2024Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear.
METHODS
We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212).
RESULTS
From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence).
CONCLUSIONS
The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Ischemic Stroke; Pyridines; Stroke; Thiazoles; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37952187
DOI: 10.1161/CIRCULATIONAHA.123.067512