Late dysfunction of a mechanical aortic valve after long-term low molecular weight heparin therapy: a case report.

Background: To date, vitamin K anticoagulants are the only recommended long-term therapy for mechanical heart valves. Bleeding episodes, thromboembolic events, and international normalized ratio monitoring are difficult and prevalent complications for these patients. This report reflects the late mechanical aortic valve dysfunction after long-term low molecular weight heparin therapy. Case summary: A 66-year-old male patient underwent mechanical aortic valve replacement in 2007. He was administered therapeutic doses of enoxaparin for nearly 12 years due to warfarin-related bleeding complications and labile international normalized ratios. However, he experienced multiple cardiovascular and cerebrovascular thromboembolic events, including an anterolateral ST-elevation myocardial infarction with left anterior descending artery thrombus, treated with thrombus aspiration and stenting. The patient was eventually admitted with symptoms and signs of acute heart failure, and echocardiography, fluoroscopy, and a cardiac computed tomography detected mechanical aortic valve prosthesis dysfunction, with an immobile leaflet and pannus. The patient demonstrated no improvement despite switching to unfractionated heparin, and he ultimately underwent redo aortic bioprosthetic valve surgery with a favourable outcome. Discussion: Low molecular weight heparin is prescribed for patients with aortic mechanical valves who are intolerant to vitamin K antagonists or as bridging in certain situations. Anti-Xa factor monitoring should be considered for long-term prescriptions.

Study of Use of Dabigatran in Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) is a challenging condition to diagnose and treat due to its diverse range of clinical presentations. The incidence of CVST is increasing, and although diagnostic techniques have improved, the mainstay of treatment is heparin followed by vitamin K antagonist (VKA), warfarin has remained largely unchanged for the past three decades. However, new direct oral anticoagulants (NOACs) like dabigatran have been developed to address the limitations of VKA therapy. Magnetic resonance imaging (MRI) with magnetic resonance venography (MRV) is the current preferred diagnostic method for CVST due to its exceptional sensitivity and specificity. This prospective observational study was set out to investigate the efficacy and safety of dabigatran in treating cerebral venous sinus thrombosis. The study included 30 patients who reported regular intake of 150 mg dabigatran etexilate twice a day. Among the participants, headache was the most commonly reported symptom. The study found that patients treated with dabigatran experienced favorable outcomes, with all patients achieving re-canalization and reporting no major complications. These promising results suggest that dabigatran could be an effective treatment option for CVST cases. However, the study emphasizes the need for larger, multi-center studies to further validate these findings and improve the overall understanding of the condition and its treatment options.

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

Background: Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation. Objectives: The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations. Methods: This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling. Conclusion: Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials.

Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature.

Atrial fibrillation (AF) is a predominant contributor to morbidity and mortality, and stroke prevention remains the mainstay for the management of AF. The precise mechanism involved in thrombus formation remains unknown. However, factors such as stretch-induced fibrosis, endothelial dysfunction, disordered atrial contractions, and pro-thrombotic states have been postulated for the development of AF. Various risk assessment strategies have been acknowledged for determining the risk of stroke in AF, of which the congestive heart failure, hypertension, age ≥75, diabetes, stroke, vascular disease, age between 65-74, and female sex (CHA2DS2-VASc) score remains the ultimate risk stratification tool. For the longest time, vitamin K antagonists (VKA) were the only oral anticoagulants available but were associated with an increased risk of bleeding. Recently, direct oral anticoagulants (DOACs) were approved and considered more efficient and safer than or as secure as warfarin in stroke prevention and lowering intra-cranial bleeding events. The pharmacodynamics and pharmacokinetics of DOACs were also clarified in this article. This review article compiles current evidence-based data on the role of DOACs, uncovering their underlying mechanisms, and comparing their efficacy with warfarin in stroke prevention in AF.

The association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation.

BACKGROUND: The impact of post-stroke antithrombotic regimen in atrial fibrillation (AF) is uncertain. OBJECTIVE: To describe antithrombotic therapy prescribing patterns following ischemic stroke, and its impact on outcomes. METHODS: A total of 23,165 AF patients experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite outcomes. RESULTS: Among those who were non-anticoagulated before a stroke, 33.5% remained non-anticoagulated and 39.2% were prescribed only antiplatelets (AP) post-stroke. Compared to NOACs post-stroke, there was a significant increase in ischemic stroke and mortality in non-anticoagulated (aHRs 2.09 and 3.92) and antiplatelet users (aHRs 1.32 and 1.28). Post-stroke warfarin was associated with a significantly incresaed risk of major bleeding compared to NOACs (aHR 1.23). Among 769 patients receiving NOACs before stroke and continuing NOAC post-stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR 2.07) and composite outcomes (aHRs 1.36-1.85) with no difference in ICH, major bleeding or mortality compared to those on the same NOAC post-stroke. Among patients receiving NOACs before stroke, the risks of clinical events were similar between patients on NOACs alone and those on NOAC plus AP post-stroke. CONCLUSIONS: NOAC alone post-stroke was associated with a better clinical outcome compared to non-anticoagulation, AP or warfarin. Among patients already taking NOACs before stroke, the addition of AP didn't confer additional benefits compared to NOACs alone. A change of NOAC types post-stroke was associated with a two-fold higher risk of ischemic stroke and composite outcomes.

Early anti-coagulation therapy in new-onset atrial fibrillation after coronary artery bypass grafting: a randomized trial pilot study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) surgery, increasing the risk of embolism and stroke. There is a lack of information on the use of anticoagulants in this context. The choice between Warfarin and Direct oral anticoagulants (DOACs) also is not well-established. This randomized study aimed to compare the feasibility and safety of Warfarin and Rivaroxaban in preventing thrombotic events in POAF patients after isolated CABG. METHODS: A total of 66 patients were randomized parallelly with 1:1 allocation to receive either Rivaroxaban (n = 34) or Warfarin (n = 32). Major bleeding events within 30 days after discharge were the primary outcome. Secondary outcomes included minor bleeding events and thrombotic episodes. Clinical characteristics, medication regimens, and left atrial diameter were assessed. Statistical analyses were performed using appropriate tests. RESULTS: No thrombotic episodes were observed in either treatment arm. No major bleeding events occurred in either group. Four minor bleeding events were reported, with no significant difference between the treatment groups (P = 0.6). Patients with atrial fibrillation had significantly larger left atrial diameters compared to those with normal sinus rhythm (40.5 vs. 37.8 mm, P = 0.01). CONCLUSIONS: This pilot study suggests that Warfarin and Rivaroxaban are both safe and effective for preventing thrombotic episodes in POAF patients after isolated CABG. No significant differences in major bleeding events were observed between the two anticoagulants. These findings may support the preference for DOACs like Rivaroxaban due to their convenience and easier maintenance. TRIAL REGISTRATION: Number IRCT20200304046696N1, Date 18/03/2020 https//irct.behdasht.gov.ir/ .

Cost-Effectiveness Analysis of Pharmacogenomics-Guided Versus Standard Dosing of Warfarin in Patients with Mechanical Prosthetic Heart Valve.

Background: Warfarin is the only approved anticoagulant for antithrombotic treatment in patients with mechanical prosthetic heart valves (MPHV). However, dosing warfarin is challenging due to its narrow therapeutic window and highly variable clinical outcomes. Both low and high doses of warfarin can lead to thrombotic and bleeding events, respectively, with these complications being more severe in individuals with sensitive genetic polymorphisms. Incorporating genetic testing could enhance the accuracy of warfarin dosing and minimize its adverse events. Objectives: This study aims to evaluate the utilities and cost-effectiveness of pharmacogenomics-guided versus standard dosing of warfarin in patients with MPHV in Iran. Methods: In this economic evaluation study, a cost-effectiveness analysis was conducted to compare pharmacogenomics-guided versus standard warfarin dosing. Data related to quality of life (QoL) were collected through a cross-sectional study involving 105 randomly selected MPHV patients using the EuroQol-5D (EQ-5D) Questionnaire. Costs were calculated with input from clinical experts and a review of relevant guidelines. Additional clinical data were extracted from published literature. The pharmacoeconomic threshold set for medical interventions within Iran's healthcare system was $1,500. A decision tree model was designed from the perspective of Iran's healthcare system with a one-year study horizon. Sensitivity analyses were also performed to assess the uncertainty of input parameters. Results: The utility scores derived from the questionnaire for standard and pharmacogenomics-guided warfarin treatments were 0.68 and 0.76, respectively. Genotype-guided dosing of warfarin was more costly compared to the standard dosing ($246 vs $69), and the calculated incremental cost-effectiveness ratio (ICER) was $2474 per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that our model is sensitive to the percentage of time in the therapeutic range (PTTR), the cost of genetic tests, and the utility of both pharmacogenomics-guided and standard dosing arms. However, the probabilistic sensitivity analysis demonstrates the robustness of our model. Conclusions: Warfarin dosing with pharmacogenomics testing is currently not cost-effective. However, if the cost of genotyping tests decreases to $118, the ICER would become cost-effective.

Interference of lupus anticoagulant causing antiprothrombin and anti-beta-2-glycoprotein I antibodies on international normalized ratio measurements: comparative analysis of international normalized ratio methods.

Background: Life-long vitamin K antagonist (VKA) therapy is recommended as a standard of care in antiphospholipid syndrome (APS) patients with thrombosis. Concerns have been raised about the validity of international normalized ratio (INR) measurements in lupus anticoagulant (LA)-positive APS patients because LA may interfere with phospholipid-dependent coagulation tests and could elevate INR measurements. Objectives: Here, we aimed to determine the interference of antigen-specific monoclonal and isolated patient antibodies with LA activity on INR measurements. Methods: Pooled normal plasma and control plasma from patients on VKA (without LA) were incubated with monoclonal and isolated patient immunoglobulin G antiprothrombin and anti-beta-2-glycoprotein I antibodies that express LA activity. INR was determined before and after addition using 3 laboratory assays (Owren STA-Hepato Prest, Quick STA-NeoPTimal, and Quick STA-Neoplastine R) and 1 point-of-care test device (CoaguChek Pro II). Results: Antiprothrombin and anti-beta-2-glycoprotein I antibodies with LA activity interfered with recombinant human thromboplastin reagents (Quick STA-Neoplastine R and CoaguChek Pro II), particularly when added to plasma of VKA-treated controls. This effect was most evident on point-of-care test INR measurements, while the recombinant Quick reagent exhibited a lesser degree of interference. In contrast, tissue-derived thromboplastin reagents (Owren STA-Hepato Prest and Quick STA-NeoPTimal) remained largely unaffected by these antibodies, both in pooled normal plasma and VKA anticoagulated control plasma. Among these reagents, the Owren INR reagent exhibited the lowest sensitivity to the influence of LA antibodies. This observed difference in sensitivity is independent of the plasma dilution factor or the presence of factor V or fibrinogen in Owren reagent. Conclusion: INR reagents that utilize recombinant human thromboplastin are more sensitive to the presence of monoclonal and patient-derived antibodies with LA activity. Consequently, APS patients positive for LA should be monitored using tissue-derived thromboplastin reagents, given its reduced susceptibility to interference by LA-causing antibodies.

Management of Patients Receiving Anticoagulation Therapy in Dental Practice: A Systematic Review.

BACKGROUND: Anticoagulant drugs are a valuable tool for minimizing thrombotic risks in at-risk patients. The purpose of this study is to conduct a literature review highlighting the management of these drugs during daily clinical dental practice. MATERIALS AND METHODS: We limited our search to English-language papers published between 1 January 1989, and 7 March 2024, in PubMed, Scopus and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "anticoagulant AND dentistry" were used. RESULTS: Twenty-five clinical trials were included for final review from 623 articles obtained from the databases Web of Science (83), PubMed (382), and Scopus (158), eliminating duplicates and 79 off-topic items, resulting in 419 articles after removing 315 entries and confirming eligibility. Overall, these studies support the use of local hemostatic measures to manage the risk of bleeding in patients on anticoagulant therapy undergoing dental procedures and highlight the importance of greater education and collaboration among healthcare professionals. CONCLUSIONS: Research and clinical investigation have improved understanding and management of dental procedures in patients undergoing anticoagulant or antiplatelet therapy. Hemostatic agents, clinical protocols, risk factors, and continuous education are essential for navigating the complexities of anticoagulant therapy, ensuring optimal outcomes and enhancing patient well-being.

Early Versus Late Post Cesarean Section Warfarin Initiation and Increased Risk of Maternal Complications in Patients With Mechanical Heart Valves: A Randomized, Open-Label Pilot Study.

BACKGROUND AND OBJECTIVES: The timing of the reinstitution of warfarin after cesarean section (CS) delivery was not adequately addressed in the literature. This study aims to evaluate the risks of early versus late initiation of warfarin post-CS in patients with mechanical heart valves. METHODS: This randomized, open-label cohort study included 114 pregnant women with mechanical heart valves planned to be delivered by CS at or after 28 weeks of gestation. Patients were randomly divided into two groups: Day-2-group, where warfarin was started on day 2, and Day-5-group, where warfarin was started on day 5 after CS. Maternal postoperative bleeding complications, mechanical valve thrombosis, need for blood transfusion or reoperation, and maternal mortality were identified. RESULTS: Ten women (8.8%) had 11 bleeding complications, of whom 2 patients (20%) had intraperitoneal hemorrhage (none in Day-2-group and 2 in Day-5-group), 3 patients (30%) had subcutaneous hematoma (none in Day-2-group and 3 in Day-5-group), and 6 patients (60%) had sub-rectus hematoma (3 in Day-2-group and 3 in Day-5-group). No mechanical valve thrombosis, other thromboembolic events, or in-hospital maternal mortality were reported. CONCLUSION: Despite the small number of events, the bleeding risk was lower in the group with early post-CS warfarin introduction than in the group with late warfarin introduction in patients with prosthetic heart valves. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04855110.

Efficacy of topical tranexamic acid soaked absorbable gelfoam in relieving post-extraction pain in warfarin patients: a randomized, triple-blinded, split-mouth, active-controlled clinical trial.

BACKGROUND: Warfarin patients who need dental extraction face the problem of bleeding and no sufficient hemostasis results in dry socket and postoperative pain. This study aimed to evaluate and compare the efficacy of the topical application of tranexamic acid-soaked absorbable Gelfoam (TXA-Gel) and saline-soaked absorbable Gelfoam (saline-Gel) in relieving postoperative pain following bilateral simple extraction of permanent mandibular molars in warfarin patients. METHODS: This was a randomized, triple-blinded, split-mouth, active-controlled clinical trial. It was performed at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Damascus University, between November 2021 and October 2023. 60 bilateral permanent mandibular molars, which were indicated for simple extraction in 30 warfarin patients randomly assigned into two groups according to the topical hemostatic agents after extraction used: Group 1: control group, saline-Gel (n = 30). Group 2: TXA-Gel (n = 30). A simple randomization method was performed by flipping a coin. The primary outcome measure was the visual analogue scale (VAS). The intensity of pain was evaluated at the baseline (t0), and on the 1st (t1), 2nd (t2), 3rd (t3), 4th (t4), 5th (t5), 6th (t6), and 7th (t7) days following extraction. The Kolmogorov-Smirnov test and the Mann-Whitney U test were performed. The level of significance was set at 0.05 (p < 0.05). RESULTS: The mean vas scores was 4.17 ± 1.76 at t1 and decreased to 0.73 ± 0.78 at t7 in the TXA-Gel group. However, in the Gelfoam group, the mean vas scores was 4.83 ± 2.18 at t1 and decreased to 1.80 ± 1.00 at t7. The results of the Mann-Whitney U test showed that there was no statistically significant difference between the two groups at t1 (p = 0.236) and t2 (p = 0.155). However, there was a statistically significance difference at the rest time points (p < 0.05). CONCLUSIONS: TXA-Gel played a prominent role in alleviating post-extraction pain in warfarin patients. TRIAL REGISTRATION: The trail was retrospectively registered at the ISRCTN registry (ISRCTN71901901).

Randomized Comparison of Progression of Atherosclerotic Plaques and Calcification of Coronary Artery in Atrial Fibrillation Patients Treated With Edoxaban Versus Warfarin (The REPRESENT-AF trial).

Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

Risk of ocular neovascular conversion and systemic bleeding complications in patients with AMD on DOACs or Warfarin.

PURPOSE: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM). METHODS, INTERVENTION, OR TESTING: TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities. MAIN OUTCOME MEASURES: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy. RESULTS: Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years. CONCLUSIONS: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs.

Comparison between non-vitamin K oral antagonist versus warfarin in atrial fibrillation with and without valvular heart disease: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) poses a significant stroke risk in heart disease patients. This systematic review aims to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) versus vitamin K antagonists (VKAs) in AF patients with and without any valvular heart disease (VHD/N-VHD). METHODS: A systematic search was conducted on PubMed, Scopus, and Google Scholar up to March 3, 2022. Efficacy and safety parameters were analyzed. RESULTS: A total of 85,423 subjects from 10 studies were included in this meta-analysis. NOACs and VKAs showed similar effects on ischemic stroke in AF patients with VHD/N-VHD (RR 0.97; 95% CI 0.72-1.30; p = 0.83) and also on systemic embolic events (RR 1.02; 95% CI 0.83-1.25; p = 0.86). Similar effects were seen in VHD and N-VHD subgroups. Both treatments had similar effects on myocardial infarction in AF patients with VHD/N-VHD (RR 0.79; 95% CI 0.49-1.26; p = 0.32), VHD (RR 0.78; 95% CI 0.59-1.02; p = 0.07), and N-VHD subgroups (RR 0.82; 95% CI 0.30-2.21; p = 0.69). NOACs reduced the risk of intracranial bleeding in AF VHD/N-VHD (RR 0.64; 95% CI 0.54-0.77; p < 0.0001), VHD (RR 0.59; 95% CI 0.42-0.82; p = 0.002), and N-VHD subgroups (RR 0.70; 95% CI 0.57-0.85; p = 0.0003). Additionally, NOACs reduced the risk of gastrointestinal bleeding in AF VHD/N-VHD (RR 0.80; 95% CI 0.66-0.96; p = 0.02), specifically in the VHD subgroup (RR 0.69; 95% CI 0.54-0.89; p = 0.004). Moreover, NOACs were associated with a decreased risk for minor and non-fatal bleeding in AF patients with VHD/N-VHD (RR 0.86; 95% CI 0.75-0.99; p = 0.04). CONCLUSION: NOACs are effective and safe for ischemic stroke, systemic embolic events, myocardial infarction, intracranial bleeding, and gastrointestinal bleeding in AF patients with VHD/N-VHD.

Determination of warfarin in volumetric absorptive microsampling by liquid chromatography-tandem mass spectrometry.

Objective: This study aims to develop and validate bioanalytical method for quantifying warfarin in VAMS samples using liquid chromatography tandem mass spectrometry (LC-MS/MS), directly implementing the method to patients receiving warfarin therapy. Methods: The UPLC-MS/MS method was developed and optimized, with quercetin as the internal standard. Sample preparation was carried out using protein precipitation with methanol-acetonitrile (1:3 v/v). Results: Chromatographic separation was achieved using Acquity® UPLC BEH C18 column with 0.1 % formic acid-acetonitrile-methanol (30:69:1 v/v) as mobile phase, in isocratic elution. Multiple Reaction Monitoring (MRM) detection was done using m/z values of 307.10 â†’ 161.06 for warfarin and 301.03 â†’ 150.98 for quercetin as internal standard, using Electrospray Ionization (ESI) negative ion source. The clinical application of the bioanalytical method was carried out on 25 patients receiving warfarin therapy at Universitas Indonesia Hospital and warfarin levels were well within the calibration range from 6.05 to 431.39 ng/mL. Conclusion: A novel method has been developed to analyze warfarin in VAMS samples. This method has been fully validated according to guideline from FDA 2022 and is linear in the range of 5-500 ng/mL and the value of r ≥ 0.9977, and successfully applied for the analysis of warfarin in VAMS samples of clinical patients.

Updated Assessment of Practice Patterns of Perioperative Management of Antiplatelet and Anticoagulant Therapy in Interventional Pain Management.

BACKGROUND: The role of antiplatelet/anticoagulant therapy is well known for its primary and secondary prevention of sequela from cardiovascular disease by decreasing the incidence of acute cerebral, cardiovascular, peripheral vascular, and other thrombo-embolicevents. The overwhelming data show that the risk of thrombotic events is significantly higher than that of bleeding during surgery after antiplatelet drug discontinuation. It has been assumed that discontinuing antiplatelet therapy prior to performing interventional pain management techniques is a common practice, even though doing so may potentially increase the risk of acute cerebral and cardiovascular events. A survey of practice patterns was conducted in 2012, since then the risks associated with thromboembolic events and bleeding, has not been systematically evaluated. OBJECTIVE: To conduct an updated assessment of the perioperative antiplatelet and anticoagulant practice patterns of U.S. interventional pain management physicians and compare this with data collected in 2012 with 2021 data regarding practice patterns of continuing or discontinuing anticoagulant therapy. STUDY DESIGNn: Postal survey of interventional pain management physicians. STUDY SETTING: Interventional pain management practices in the United States. METHODS: The survey was conducted based on online responses of the members of the American Society of Interventional Pain Physicians (ASIPP) in 2021. The survey was designed similar to the 2012 survey to assess updated practice patterns. RESULTS: The questionnaire was sent out to 1,700 members in October 2021. Out of these, 185 members completed the survey, while 105 were returned due to invalid addresses. The results showed that 23% changed their practice patterns during the previous year. The results also showed that all physicians discontinued warfarin therapy with the majority of physicians accepting an INR of 1.5 as a safe level. Low dose aspirin (81 mg) was discontinued for 3 to 7 days for low-risk procedures by 8% of the physicians, 34% of the physicians for moderate or intermediate risk procedures, whereas they were discontinued by 76% of the physicians for high-risk procedures. High dose aspirin (325 mg) was discontinued at a higher rate. Antiplatelet agents, including dipyridamole, cilostazol, and Aggrenox (aspirin, extended-release dipyridamole) were discontinued from 3 to 5 days by 18%-23% of the physicians for low-risk procedures, approximately 60% of the physicians for moderate or intermediate-risk procedures, and over 90% of the physicians for high-risk procedures. Platelet aggregation inhibitors clopidogrel, prasugrel, ticlopidine, and ticagrelor were discontinued for 3 to 5 days by approximately 26% to 41% for low-risk procedures, almost 90% for moderate or intermediate-risk procedures, and over 97% for high-risk procedures. Thrombin inhibitor dabigatran was discontinued by 33% of the physicians for low-risk procedures, 92% for moderate or intermediate-risk procedures, and 99% for high-risk procedures. Anti-Xa agents, apixaban, rivaroxaban, and Edoxaban were discontinued in over 25% of the physicians for low-risk procedures, approximately 90% for moderate or intermediate-risk procedures, and 99% for high-risk procedures. LIMITATIONS: This study was limited by its being an online survey of the membership of one organization in one country, that there was only a 11.6% response rate, and the sample size is relatively small. Underreporting in surveys is common. Further, the incidence of thromboembolic events or epidural hematomas was not assessed. CONCLUSION: The results in the 2021 survey illustrate a continued pattern of discontinuing antiplatelet and anticoagulant therapy in the perioperative period. The majority of discontinuation patterns appear to fall within guidelines.

Knowledge, Attitude and Practice Toward Intracerebral Hemorrhage Prevention Among Patients Taking Oral Anticoagulants.

Background: Intracerebral hemorrhage (ICH) affects up to 1% of chronic oral anticoagulation (OAC) users per year. This study explored the knowledge, attitude and practice (KAP) towards ICH prevention among patients taking OACs. Methods: This multicenter cross-sectional survey was conducted at 4 hospitals from February to May 2023, and a self-administered questionnaire was developed to assess KAP toward ICH prevention among patients taking OACs. Structural equation modeling was used to assess the relationship between KAP. Results: A total of 536 valid questionnaires (67.25%) were analyzed, from 43.8% participants on Warfarin, 40.5% on Rivaroxaban and 15.7% on Dabigatran. The average knowledge, attitudes and practice scores were 9.22, 24.11, and 28.01 out of 16, 35 and 40, respectively. Participants who received Rivaroxaban had lower knowledge scores but higher attitude and practice store compared to those who received Warfarin or Dabigatran (all p < 0.001). According to Structure Equation Modeling, attitude had direct positive effect on practice (ß = 0.694 [0.603-0.804], p = 0.012), while knowledge had direct negative effect on attitude (ß = -2.077 [-2.507-1.651], p = 0.013), as well as negative effect on practice, both direct (ß = -0.450[-0.689-2.03], p=0.012), and indirect (ß = -1.441 [-1.928-1.192], p = 0.004). Conclusion: Patients taking OACs showed insufficient knowledge, negative attitude and proactive practice regarding ICH; practice scores were affected by age, type of anticoagulation medication, and attitude rather than knowledge.

Comparative effectiveness of warfarin management strategies: a systematic review and network meta-analysis.

Background: The management of warfarin therapy presents clinical challenges due to its narrow therapeutic index. We aimed to evaluate the comparative effectiveness of different management strategies in patients using warfarin. Methods: PubMed, Embase, Cochrane CENTRAL, CINAHL, and EBSCO Open Dissertation were searched from inception to 8 May 2024. Randomized controlled trials that compared the following interventions: patient self-management (PSM), patient self-testing (PST), anticoagulation management services (AMS), and usual care in patients prescribed warfarin for any indication were included. Risk ratios (RR) with 95% confidence interval (CI) were estimated using a random-effects model. Surface under the cumulative ranking curves (SUCRA) were used to rank different interventions. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) online platform. This study is registered with PROSPERO (CRD42023491978). Findings: Twenty-eight trials involving 8100 participants were included, with follow-up periods of 1-24 months. Mean warfarin dosages were 4.9-7.2 mg/day. Only PSM showed a significant reduction of major TE risk compared with usual care (RR = 0.41; 95% CI: 0.24, 0.71; I2 = 0.0%) with moderate certainty of evidence. The 97.6% SUCRA also supported the beneficial effects of PSM over other interventions. The combined direct and indirect evidence showed significantly higher TTR in PSM compared with usual care (MD = 7.39; 95% CI: 2.39, 12.39), with very low certainty. However, direct evidence showed non-significant TTR improvement (MD = 6.49; 95% CI: -3.09, 16.07, I2 = 96.1%). No differences across various strategies were observed in all-cause mortality, major bleeding, stroke, transient ischemic attack, and hospitalization. Interpretation: PSM reduces the risk of major TE events compared with usual care, tends to improve anticoagulation control, and should be considered where appropriate. Funding: Agency for Healthcare Research and Quality (grant ID 5R18HS027960).

Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.