Warfarin For Prevention Of Thromboembolism Research Articles

Free-floating thrombus of the aorta: 3 case reports

BackgroundIdiopathic free-floating thrombus (FFT) of the aorta is a rare occurrence, but it can lead to catastrophic consequences. The initial symptoms are typically cerebral or peripheral embolisms. Surgical thrombectomy and thrombolysis are two primary treatments for FFT. Here, we report three cases of patients with idiopathic FFT in the absence of coagulopathy who were treated successfully by surgery with no recurrent thrombi or relapse of symptoms.Case presentationCase 1 involved a 72-year-old male patient with a pedunculated thrombus in the distal aortic arch. Case 2 involved a 62-year-old female patient with a cylinder thrombus in the aortic arch and left common carotid artery. Case 3 involved a 65-year-old male patient with three pedunculated thrombi in the ascending aorta, aortic arch, and left subclavian artery. None of the patients had clinical signs of coagulopathy. Pedunculated or cylinder thrombi have a greater risk of breaking off, which can produce severe peripheral embolism in contrast with intramural thrombi (73% vs. 12%). Due to the high embolism risk for each patient, conservative medical treatment by heparinization was deemed inappropriate, so each patient underwent emergency surgical thrombus removal. After surgery, each of the three patients was treated with warfarin for secondary prevention of thromboembolism. At 7-month follow-up in outpatient practice, a computed tomography (CT) scan indicated that Patient 1 had no recurrent thrombus, and the patient has been symptom-free for 11 months. At 1-month follow-up in outpatient practice, a CT scan indicated that Patient 2 had no recurrent thrombus, and the patient has been symptom-free for 8 years. At 3-week follow-up in hospital, a CT scan indicated that Patient 3 had no recurrent thrombus, but he failed to follow-up after discharge, so his follow-up status is unknown.ConclusionsFor a large pedunculated or cylinder thrombus located in the thoracic aorta, surgical thrombectomy should be performed. And, in surgical thrombectomy, the location of the cannulas and cross-clamp should be selected carefully according to the location of the thrombus. After surgery, anticoagulant is important to prevent recurrent idiopathic thrombi.

Rivaroxaban versus Warfarin for Prevention of Thromboembolism in Bangladeshi Patients with Non-Valvular Atrial Fibrillation

Background: The use of Warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulant effects than Warfarin.
 Methods: In this Open comparison trial, the researchers compared Rivaroxaban (at a daily dose of 20 mg or 15 mg daily in patient with a creatinine clearance of 30-49 ml/min ) with dose adjusted Warfarin (target INR 2.0 to3.0) in 2,846 patients with nonvalvular atrial fibrillation and CHA2DS2-VASc Score 2 or more. The primary efficacy outcome was stroke or systemic embolism and primary safety outcome was major or minor bleeding. This research was designed to determine whether Rivaroxaban have more efficacy and safety than Warfarin for the primary outcomes.
 Results: Total follow-up period was 6 months. Risk factors and co-morbidities were similar in both groups. Baseline investigations were also similar. Age and sex of both groups were matched. The rate of ischaemic stroke was 1.8% in Rivaroxaban group, as compared with 2.18% in the Warfarin group (p 0.479, nonsignificant). The rate of haemorrhagic stroke was 0.53% in Rivaroxaban group, as compared with 1.36 % in the Warfarin group (p 0.026, significant). Systemic embolism was 0.08% in Rivaroxaban group, as compared with 0.15 % in the Warfarin group (p 0.561, non-significant). The rate of major bleeding was 0.4% in Rivaroxaban group and 0.53 % in the Warfarin group (p 0.361, non-significant). The rate of minor bleeding was 2.10% in Rivaroxaban group, as compared with 2.33% in the Warfarin group (p 0.681, non-significant).
 Conclusions: Rivaroxaban have similar efficacy and better safety profile than Warfarin in patients with nonvalvular atrial fibrillation in Bangladeshi population.
 University Heart Journal Vol. 16, No. 2, Jul 2020; 99-105

P4777Mortality in patients with non-valvular atrial fibrillation in South America. Warfarin has significant higher global mortality rates versus dabigatran and rivaroxaban

Abstract Background Oral anticoagulants are the cornerstone for the management of atrial fibrillation (AF) to reduce cardioembolic stroke Randomized controlled trials of anticoagulants have shown non-inferiority of direct oral anticoagulants (DOACs) compared to warfarin Most DOACs represent an advance in therapeutic safety when compared to warfarin for prevention of thromboembolism in patients with AF. Objectives Determine long term survival, total mortality rates and mortality cause between patients with non-valvular atrial fibrillation (AF) receiving anticoagulants (warfarin, dabigatran and rivaroxaban) Methods Retrospective analysis of consecutive patients with AF receiving anticoagulants in two Hospitals in Montevideo, using electronic registries. Demographics, co-morbidities, CHA2DS2VASc scores and mortality cause were annotated. Follow-up started on Jan 2011 and finished on Dec 2017. Anticoagulation quality was expressed as the standard deviation of INRs (SD-INRs). We performed global mortality and mortality cause analysis on patients with anti-VitK versus direct anticoagulants. Statistical analysis: Survival analysis was performed using Kaplan-Meier (log rank) and Cox regression model. All differences between groups were considered significant if the p value was <0.001. Results We studied 4501 pts., 3627 patients were on warfarin (80.6%), 456 (10.1%) were on dabigatran and 418 (9.3%) on rivaroxaban. Those receiving direct anticoagulants were older, 79±9 vs 77±11 years, (p=0.0001), 51.3% were female, with a significantly higher prevalence of HTN; 93.7% vs 88.8% and a CHA2DS2VASc score ≥2 (96% vs 91%), and a lower prevalence of CHD (5.8% vs 10.4%), CHF (3.7% vs 9.5%) and CKD (2.3% vs 6.3%).Total mortality was 818 (18%); patients receiving warfarin had significantly higher mortality rates, 727 (20.1%) vs 91 (10.4%); 63 and 28 (13.8%, 6.7% dabigatran and rivaroxaban respectively) Kaplan-Meier curves were significantly different (Figure 1) showing higher survival rates for those on DOACs. The SD-INRs were 0.85±0.47 (n=1726 alive) vs 1.05±0.46 (n=548 dead), mean difference 0.2 (99% CI 0.14–0.26). Mortality could be analysed in 759 patients (92,7%). The most important cause of death was cardiovascular disease in 26.5%. We could not find significant differences in the cause of death between groups. Using Cox regression model, variables with significant increased mortality were HTN, CHD, CHF, CKD and history of previous CVA. The only variable with a significant decrease in mortality was the use of dabigatran or rivaroxaban; HR 0.55 (95% CI 0.44–0.69) Figure 1 Conclusions In this large cohort of patients, those receiving warfarin have significantly higher mortality rates. Mortality differences were not related to stroke or major bleeding but could be explained by a higher prevalence of CHD, CHF and CKD in the warfarin group despite a significant lower CHA2DS2VASc score.

A single institution’s experience with using dabigatran, rivaroxaban and warfarin for prevention of thromboembolism in atrial fibrillation

Background:Although non-vitamin K antagonist oral anticoagulants (NOACs) are approved for stroke prevention in atrial fibrillation (AF) patients, their use in the local clinical setting has not been well studied. This study aims to evaluate the clinical outcomes of dabigatran, rivaroxaban and warfarin in a tertiary hospital in Singapore.Methods:This is a retrospective cohort study with one-year follow-up. A total of 383 patients recruited between June 2011 and December 2014 were studied. Incidents of stroke, systemic embolism and clinically relevant bleeding events were compared between dabigatran, rivaroxaban and warfarin.Results:Stroke rates were 5.47% per year with warfarin, 7.27% per year with dabigatran (HR=1.32; 95% CI 0.48−3.64; p=0.591) and 2.76% per year with rivaroxaban (HR=0.49; 95% CI 0.14−1.69; p=0.261). The warfarin group had significantly higher incidence of minor bleeding (62.4% vs 3.64% for dabigatran vs 13.79% for rivaroxaban; p<0.001), major bleeding (3.91% for warfarin, 0.91% for dabigatran, 0% for rivaroxaban; p=0.028) and other adverse events (51.18% for warfarin, 3.64% for dabigatran, 8.28% for rivaroxaban; p<0.001). Incidence of dyspepsia was higher in both NOAC groups compared to warfarin (0% for warfarin, 7.27% for dabigatran, 5.52% for rivaroxaban; p=0.003).Conclusion:Stroke and venous thromboembolism rates after one year were comparable among dabigatran, rivaroxaban and warfarin. Warfarin was associated with more bleeding and adverse events while both NOACs were associated with higher rates of dyspepsia. Further study is needed to assess the clinical benefit of NOACs in the Singaporean population.

Abstract 078: Implications of Patient-Reported Treatment Satisfaction for Discontinuation of Rivaroxaban versus Warfarin in ROCKET-AF

Background: Patient-reported outcomes and satisfaction are important in both trials and clinical practice and may be associated with treatment adherence. Methods: ROCKET-AF was a randomized, double-blind trial of rivaroxaban versus warfarin for prevention of thromboembolism in patients with atrial fibrillation. In a substudy, we compared treatment satisfaction scores: Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). Patient-driven discontinuation included stopping study drugs due to withdrawal of consent, non-compliance, or loss to follow-up. Rates of discontinuation were calculated for participants above and below the median scores for each scale. Results: Of 14,264 patients in ROCKET AF, 1,181 (8.3%; median age 75 years; 34% women) patients completed both the ACTS and TSQM II questionnaires 4 weeks after starting the study drug. Over a median follow-up of 1.6 years, 450 premature study drug discontinuations occurred, 116 (26%) patient-driven. Patients less satisfied with treatment by the ACTS Benefits and Burdens and TSQM II scales had higher rates of study drug discontinuation ( Table ). Conclusions: Patient-reported satisfaction was lower in patients with study drug discontinuation, suggesting that collecting patient-reported outcomes early in clinical trials may guide interventions that improve adherence and clinical outcomes.

Percutaneous closure of the left atrial appendage for prevention of thromboembolism in atrial fibrillation for patients with contraindication to or failure of oral anticoagulation: A single-center experience

IntroductionIn non-valvular atrial fibrillation 90% of thrombi originate in the left atrial appendage (LAA). Percutaneous LAA closure has been shown to be non-inferior to warfarin for prevention of thromboembolism. ObjectiveTo evaluate the initial experience of a single center in percutaneous LAA closure in patients with high thromboembolic risk and in whom oral anticoagulation was impractical or contraindicated or had failed. MethodsPatients with non-valvular atrial fibrillation and CHADS2 score ≥2 in whom oral anticoagulation was impractical or contraindicated or had failed underwent percutaneous LAA closure according to the standard technique. After the procedure, dual antiplatelet therapy was maintained for one month, followed by single antiplatelet therapy indefinitely. Patients were followed by clinical assessment and transthoracic and transesophageal echocardiography. ResultsThe procedure was performed in 22 of the 23 selected patients (95.7%), mean age 70±9 years, CHADS2 score 3.2±0.9 and CHA2DS2-VASC score 4.7±1.4. Intraprocedural device replacement was necessary only in the first patient, due to oversizing. The following periprocedural complications were observed: one femoral pseudoaneurysm, three femoral hematomas and two minor oropharyngeal bleeds, resolved by local hemostatic measures. During a 12±8 month follow-up a mild peri-device flow and a thrombus adhering to the device, resolved under with enoxaparin therapy, were identified. The rate of transient ischemic attack (TIA)/stroke was lower than expected according to the CHADS2 score (0 vs. 6.7±2.2%). ConclusionsIn our initial experience, this procedure proved to be a feasible, safe and effective alternative for atrial fibrillation patients in whom oral anticoagulation is not an option. Only relatively minor complications were observed, with a lower than expected TIA/stroke rate.

Encerramento percutâneo do apêndice auricular esquerdo para profilaxia de tromboembolismo na fibrilhação auricular em doentes com contraindicação ou falência da hipocoagulação oral: experiência de um serviço

IntroductionIn non-valvular atrial fibrillation 90% of thrombi originate in the left atrial appendage (LAA). Percutaneous LAA closure has been shown to be non-inferior to warfarin for prevention of thromboembolism. ObjectiveTo evaluate the initial experience of a single center in percutaneous LAA closure in patients with high thromboembolic risk and in whom oral anticoagulation was impractical or contraindicated or had failed. MethodsPatients with non-valvular atrial fibrillation and CHADS2 score ≥2 in whom oral anticoagulation was impractical or contraindicated or had failed underwent percutaneous LAA closure according to the standard technique. After the procedure, dual antiplatelet therapy was maintained for one month, followed by single antiplatelet therapy indefinitely. Patients were followed by clinical assessment and transthoracic and transesophageal echocardiography. ResultsThe procedure was performed in 22 of the 23 selected patients (95.7%), mean age 70±9 years, CHADS2 score 3.2±0.9 and CHA2DS2-VASC score 4.7±1.4. Intraprocedural device replacement was necessary only in the first patient, due to oversizing. The following periprocedural complications were observed: one femoral pseudoaneurysm, three femoral hematomas and two minor oropharyngeal bleeds, resolved by local hemostatic measures. During a 12±8 month follow-up a mild peri-device flow and a thrombus adhering to the device, resolved under with enoxaparin therapy, were identified. The rate of transient ischemic attack (TIA)/stroke was lower than expected according to the CHADS2 score (0 vs. 6.7±2.2%). ConclusionsIn our initial experience, this procedure proved to be a feasible, safe and effective alternative for atrial fibrillation patients in whom oral anticoagulation is not an option. Only relatively minor complications were observed, with a lower than expected TIA/stroke rate.

Cutting through the statistical fog: understanding and evaluating non-inferiority trials

Every year, results from many important randomised, controlled trials are published. Knowing the elements of trial design and having the skills to critically read and incorporate results are important to medical practitioners. The goal of this article is to help physicians determine the validity of trial conclusions to improve patient care through more informed medical decision making. This article includes a review of 162 randomised, controlled non-inferiority (n = 116) and equivalence (n = 46) hypothesis studies as well as the larger Stroke Prevention using Oral Thrombin Inhibitor in atrial Fibrillation V study and the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial. Evaluation of data from small and large trials uncovers significant flaws in design and models employed and uncertainty about calculations of statistical measures. As one example of questionable study design, discussion includes a large (n = 3922), double-blind, randomised, multicentre trial comparing the efficacy of ximelagatran with warfarin for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and additional stroke risk factors. Investigators concluded that ximelagatran was effective compared with well-controlled warfarin for prevention of thromboembolism. However, deficiencies in design, as well as concerns about liver toxicity, resulted in the rejection of the drug by the US Food and Drug Administration. Many trials fail to follow good design principles, resulting in conclusions of questionable validity. Well-designed non-inferiority trials can provide valuable data and demonstrate efficacy for beneficial new therapies. Objectives and primary end-points must be clearly stated and rigorous standards met for sample size, establishing the margin, patient characteristics and adherence to protocol.

Vertebral Artery Occlusion After Chemotherapy

To the Editor: We have read the interesting report by Periard et al about cisplatin-induced strokes.1 The role of tumors as risk factors for vascular disorders has long been established. However, there is little evidence regarding the effects of chemotherapy. Several reports describe vascular toxicity in young patients treated with cisplatin, and these studies suggest a casual link.2,3 We present a patient who experienced a stroke due to vertebral artery occlusion after chemotherapy. A 48-year-old female patient was admitted to our hospital with nausea, vomiting, and headache. The patient also complained of tingling in the left …

Ximelagatran vs Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.

Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V)

Background Ximelagatran is a novel, oral direct thrombin inhibitor under investigation as an alternative to warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation (AF). Two long-term studies in patients with AF and at least one additional risk factor for stroke are underway to compare the safety and efficacy of fixed-dose ximelagatran (36 mg bid) without coagulation monitoring with dose-adjusted warfarin (international normalized ratio 2.0–3.0). Methods SPORTIF III is a randomized, open-label, parallel-group study with blinded event assessment involving 3407 patients at 259 sites in 23 countries. SPORTIF V is similar, but with double-blind treatment allocation involving 3922 patients at 409 North American sites. The primary end point in each study is the incidence of all strokes and systemic embolic events, and the objective is to establish the noninferiority of ximelagatran relative to warfarin. Secondary end point constellations include (1) death, stroke, systemic embolism, and myocardial infarction; (2) ischemic stroke, transient ischemic attack, and systemic embolism; and (3) bleeding and treatment discontinuation. Blinded central committees adjudicate all end points and monitor patient safety. The studies commenced July 2000; enrollment ended in December 2001. Each study will accrue ≥4000 patient-years and ≥80 primary end points with a minimum per-patient exposure of 12 months. Combined analysis of both studies is also planned. Results The demographics of the 2 patient populations are similar and should allow the studies to meet the objective. Conclusions The program, the largest conducted in this indication, will determine the safety and antithrombotic efficacy of ximelagatran as an alternative to warfarin for prevention of thromboembolism in patients with AF.

Very-low-dose warfarin reduced thromboembolism in patients with metastatic breast cancer who were receiving chemotherapy

TherapeuticsSeptember 1, 1994Very-low-dose warfarin reduced thromboembolism in patients with metastatic breast cancer who were receiving chemotherapyJohn S. Kizer, MDJohn S. Kizer, MDUniversity of North Carolina, Chapel Hill, North Carolina, USA (J.S.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1994-121-2-034 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationLevine M, Hirsh J, Gent M, et al. Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet. 1994 Apr 9;343:886-9. Author, Article, and Disclosure InformationAffiliations: University of North Carolina, Chapel Hill, North Carolina, USA (J.S.K.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails September 1, 1994Volume 121, Issue 2Page: 34KeywordsAlcoholismAnticoagulant therapyBilirubinBrainBreast cancerCancer chemotherapyCancer preventionCancer treatmentChemotherapyDeep vein thrombosisHemorrhageMood disordersPeptic ulcersPlateletsSafetySurvival analysisThromboembolismThrombosisVenous thromboembolism ePublished: 9 March 2020 Issue Published: September 1, 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.Loading ...

Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer

Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1·3 to 1·9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2·6 (SD 1·2) mg for the warfarin group and the mean INR was 1·52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p=0·45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p=0·031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.