Warfarin For Secondary Prevention Research Articles

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

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.

Impact of oral anticoagulant choice for the secondary prevention of venous thromboembolism on the risk of inpatient bleeding

BackgroundRandomized trials suggest that direct oral anticoagulants (DOACs) are at least as effective as warfarin for primary treatment of VTE and that bleeding risk may be lower for some DOACs relative to warfarin. However, there is very little information regarding potential bleeding risks for DOACs versus warfarin in secondary prevention of VTE. ObjectiveThe aim of this study was to compare rates of bleeding events resulting in inpatient admissions between individuals taking apixaban, rivaroxaban, and warfarin for secondary prevention of VTE during the period 2013‐2017. MethodsWe used the IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database (IBM Watson Health, Ann Arbor, MI) to establish a retrospective cohort. Initial venous thrombolism events were defined from medical claims, and follow‐up for this cohort began 6 months after the initial event. Bleeding events resulting in inpatient admission were identified from claims data over the subsequent year of secondary prevention. ResultsA total of 69 264 individuals were identified for the cohort, with 567 bleeding events. The crude rate of bleeding was highest among warfarin users (1.47/100 person‐years; 95% confidence interval [CI], 1.24‐1.74) and lower among those on either apixaban (1.00/100 person‐years; 95% CI, 0.65‐1.54) or rivaroxaban (0.84/100 person‐years; 95% CI, 0.66‐1.08). In multivariable adjusted Cox models, those on apixaban (hazard ratio [HR], 0.80; 95% CI, 0.50‐1.29) and rivaroxaban (HR, 0.81; 95% CI, 0.59‐1.09) had somewhat lower rates of bleeding events relative to those on warfarin. ConclusionsWe found modest evidence of decreased risk of bleeding for apixaban and rivaroxaban. These estimates were relatively imprecise.

For people with antiphospholipid syndrome, how does rivaroxaban compare with standard dose warfarin for secondary prevention of thromboembolic events?

For people with antiphospholipid syndrome, how does rivaroxaban compare with standard dose warfarin for secondary prevention of thromboembolic events?

Clinical Effectiveness of Direct Oral Anticoagulants vs Warfarin in Older Patients With Atrial Fibrillation and Ischemic Stroke

Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in patients with atrial fibrillation (AF) who are at high risk. Despite demonstrated efficacy in clinical trials, real-world data of DOACs vs warfarin for secondary prevention in patients with ischemic stroke are largely based on administrative claims or have not focused on patient-centered outcomes. To examine the clinical effectiveness of DOACs (dabigatran, rivaroxaban, or apixaban) vs warfarin after ischemic stroke in patients with AF. This cohort study included patients who were 65 years or older, had AF, were anticoagulation naive, and were discharged from 1041 Get With The Guidelines-Stroke-associated hospitals for acute ischemic stroke between October 2011 and December 2014. Data were linked to Medicare claims for long-term outcomes (up to December 2015). Analyses were completed in July 2018. DOACs vs warfarin prescription at discharge. The primary outcomes were home time, a patient-centered measure defined as the total number of days free from death and institutional care after discharge, and major adverse cardiovascular events. A propensity score-overlap weighting method was used to account for differences in observed characteristics between groups. Of 11 662 survivors of acute ischemic stroke (median [interquartile range] age, 80 [74-86] years), 4041 (34.7%) were discharged with DOACs and 7621 with warfarin. Except for National Institutes of Health Stroke Scale scores (median [interquartile range], 4 [1-9] vs 5 [2-11]), baseline characteristics were similar between groups. Patients discharged with DOACs (vs warfarin) had more days at home (mean [SD], 287.2 [114.7] vs 263.0 [127.3] days; adjusted difference, 15.6 [99% CI, 9.0-22.1] days) during the first year postdischarge and were less likely to experience major adverse cardiovascular events (adjusted hazard ratio [aHR], 0.89 [99% CI, 0.83-0.96]). Also, in patients receiving DOACs, there were fewer deaths (aHR, 0.88 [95% CI, 0.82-0.95]; P < .001), all-cause readmissions (aHR, 0.93 [95% CI, 0.88-0.97]; P = .003), cardiovascular readmissions (aHR, 0.92 [95% CI, 0.86-0.99]; P = .02), hemorrhagic strokes (aHR, 0.69 [95% CI, 0.50-0.95]; P = .02), and hospitalizations with bleeding (aHR, 0.89 [95% CI, 0.81-0.97]; P = .009) but a higher risk of gastrointestinal bleeding (aHR, 1.14 [95% CI, 1.01-1.30]; P = .03). In patients with acute ischemic stroke and AF, DOAC use at discharge was associated with better long-term outcomes relative to warfarin.

Abstract TP521: Changes in D-Dimer Levels With Heparin Treatment Indicate the Recurrent Stroke Risk in Patients With Cancer Associated Hypercoagulation

Purpose: In stroke patients with cancer associated hypercoagulation, D-dimer levels were used as a marker of hypercoagulation, and heparin was reported to be more effective than warfarin for secondary prevention. After started heparin, D-dimer levels tend to decrease in such patients. However, the usefulness of D-dimer levels as an indicator of recurrent stroke has not been fully investigated. The aim of this study was to assess the usefulness of D-dimer levels in the setting of heparin treatment for stroke patients with cancer associated hypercoagulation. Methods: We retrospectively analyzed stroke patients with active cancer visited to our hospital within 7 days of onset, from 2008 to 2018. Active cancer was defined as a diagnosis of or treatment for any cancer within 6 months before stroke onset. Among the patients, we enrolled subjects who were treated with heparin and had elevated D-dimer levels (&gt;2 μg/ml). Results: A total of 54 subjects (27 men, mean age 69 years) were registered. Most frequent cancer origin was pancreas (26%). Known metastatic disease was found in 67% of patients. The median pre-heparin D-dimer levels were 11.4μg/ml (IQR 5.5-20.7), and median post-heparin D-dimer levels were 8.0μg/ml (IQR 4.1-12.6). Recurrent stroke occurred in 13% patients during treated with heparin. As compared to patients without recurrent stroke, those with recurrent stroke during heparin treatment had higher ratio of post-heparin to pre-heparin D-dimer levels (1.03 vs 0.54 ; p&lt;0.01). In logistic regression analysis, increase in the ratio of D-dimer levels (per 0.1) was significantly greater risk for stroke recurrence after adjusted for age and gender (Odds Ratio 6.5, 95%CI 1.5-43.8). Among patients without recurrent stroke, 30 patients were discontinued or changed heparin to other antithrombotic agents. Within few days of heparin discontinuation, recurrent stroke accompanied with D-dimer re-elevation was occurred in 5 patients despite of treated with other anticoagulants (Warfarin in 1 and direct oral anticoagulants in 4). Conclusions: During heparin treatment, the ratio of post-heparin to pre-heparin D-dimer levels was an indicator of recurrent stroke. After heparin was changed to other drugs, D-dimer re-elevation may be associated with recurrent stroke.

Abstract WMP85: Clinical Effectiveness of Direct Oral Anticoagulants (DOACs) vs. Warfarin in Older Ischemic Stroke Patients With Atrial Fibrillation: Findings From Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

Introduction: Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for secondary prevention in ischemic stroke patients with atrial fibrillation. Despite demonstrated efficacy in clinical trials, there are few real-world experiences of DOACs vs. warfarin in community practice. Methods: We analyzed ischemic stroke survivors with atrial fibrillation discharged from the Get With The Guidelines Stroke hospitals between 2011-2014 and linked to Medicare claims for longitudinal outcomes through 2015. A propensity score overlap weighting method was used to compare DOACs vs. warfarin. The primary outcomes were major adverse cardiovascular events (MACE) and home time, a patient-centered outcome reflecting desire of “being alive at home, without recurrent stroke, or being hospitalized for complications.” Results: Among 11,662 stroke survivors (median age 80), 4,041 (34.7%) were discharged on DOACs (dabigatran, rivaroxaban, or apixaban) and 7,621 on warfarin. Except for NIHSS (median 4 [IQR 1-9] vs. 5 [2-11]), baseline demographics, medical history, and clinical characteristics were similar between two cohorts. Compared with warfarin, patients discharged on DOACs were less likely to experience MACE (33.95% vs. 40.36% per year, adjusted hazard ratio 0.89, 99% CI 0.83-0.96) and had more days at home (mean 287 vs. 263 days during the first year post discharge, adjusted difference 15.6 days, 99% CI 9.0-22.1) ( Table ). Additionally, there were fewer deaths, all-cause readmissions, cardiovascular readmissions, hemorrhagic strokes, and bleeding hospitalizations in DOAC-treated patients, although no significant differences in fatal bleeding, ischemic stroke readmission, systemic embolism, pneumonia, or sepsis (two negative outcome controls) between the two cohorts. Conclusions: In ischemic stroke survivors with atrial fibrillation, DOACs were associated with improved long-term clinical outcomes compared with warfarin.

Neues aus der Schlaganfallmedizin

Systemic thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) remains the only effective and approved medical treatment of acute ischemic stroke. Several studies have demonstrated the importance of rapid recanalization. The efficacy of thrombectomy has so far not been sufficiently shown in randomized clinical trials; therefore, inclusion of suitable patients in one of the currently ongoing randomized trials is of great importance. The early treatment with magnesium after acute ischemic stroke during the pre-hospital phase did not prove to be neuroprotective. Intermittent pneumatic compression of the lower extremities in immobilized stroke patients effectively prevents deep venous thrombosis and pulmonary embolism. In patients with lacunar stroke the combination of aspirin and clopidogrel is not superior to aspirin alone and causes more bleeding complications. The novel oral anticoagulants are superior to warfarin in secondary prevention and carry a lower risk of intracranial and systemic bleeding complications. New studies will investigate whether dabigatran or rivaroxaban are superior to aspirin in secondary prevention after cryptogenic stroke.

Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation

The patients with non-valvular atrial fibrillation (NVAF), both permanent and paroxysmal, and history of previous transient ischemic attack (TIA) or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs) have been demonstrated to be not inferior to warfarin for many end points in NVAF patients in terms of efficacy and safety. The post hoc analysis in selected subgroups of patients enrolled in the three mega trials of phase III comparing DOACs (RE-LY, ROCKET-AF and ARISTOTLE) with warfarin help to evaluate whether superiority and non-inferiority persist in these subgroups. Here, patients with NVAF and history of previous TIA/stroke receiving DOACs as secondary prevention are compared with patients with the same characteristics receiving warfarin. An analysis of these patients has been recently published (separately for each of three DOACs). This analysis shows that DOACs maintain their non-inferiority when compared with warfarin in secondary prevention, representing a real alternative in this context of patients at high risk for ischemic and bleeding events.

New Oral Anticoagulants Are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons

PurposePatients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).MethodsThree randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.ResultsIn patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.ConclusionNOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.

Evaluation of the safety and efficacy of warfarin in Taiwanese patients

The safety and efficacy of warfarin therapeutic range in Asians remain to be ascertained. Physicians in Taiwan consider Asians are more likely to have bleeding complications rather than thromboembolic events from warfarin. The aim of this study was to determine if the proper INR range for patients in Taiwan is different. A retrospective study was conducted with 161 patients on warfarin therapy for more than 24 consecutive months during March 1, 2006 to Sepember 30, 2008. Total follow-up time was 3,504 patient-months. The incidence rates of thromboembolic and bleeding events for INR categories were calculated. The overall incidence rates of INR ranges of < 1.5, 1.5 - 1.9, 2.0 - 2.4, 2.5 - 2.9, 3.0 - 3.4, and ≥ 3.5 were 8.1, 5.6, 2.0, 7.6, 33.3, and 121.2 per 1,000 patientmonths, respectively. The overall incidence rate at INR of > 3 is higher than that at INR of < 2 or 2 - 3 (p < 0.001), with the lowest incidence rate at INR between 2.0 and 2.4. When INR was maintained at a level < 2, patients taking warfarin for secondary prevention had a significantly higher event rate compared to the primary prevention group (p < 0.05). Age greater than 73 years was a risk factor for thromboembolic events before and after covariate adjustment. An INR range of 2 - 2.4 appeared to be associated with lower complications and better clinical outcomes in Taiwanese patients treated with warfarin. Lowering the intensity of anticoagulant therapy further does not decrease the number of events.

The Association Between Prior Use of Aspirin and/or Warfarin and the In-hospital Management and Outcomes in Patients Presenting With Acute Coronary Syndromes: Insights From the Global Registry of Acute Coronary Events (GRACE)

Background The role of acetylsalicylic acid (ASA [aspirin]) and warfarin in secondary prevention after acute coronary syndromes (ACS) is well established. However, there are sparse data comparing the presentation and outcomes of patients who present with ACS while on ASA and/or warfarin therapy and those on neither. Methods Using data from the Canadian Global Registry of Acute Coronary Events (GRACE), we stratified 14,090 ACS patients into 4 groups according to prior use of antithrombotic therapies and compared in-hospital management and outcomes. Results Among 14,090 ACS patients, 7411 (52.6%) were not on prior ASA or warfarin therapy, 5724 (40.6%) were on ASA only, 593 (4.2%) were on warfarin only, and 362 (2.6%) were on both ASA and warfarin. ACS patients taking ASA and/or warfarin were older with more comorbidities than the patients on neither drug. Patients receiving prior warfarin only or ASA and warfarin were less likely to receive guideline-recommended therapies. Patients who were taking prior warfarin only had higher unadjusted rates of death, death and/or reinfarction (re-MI), congestive heart failure (CHF), and major bleeding as compared with patients on no prior therapy. Furthermore, patients who were taking ASA and warfarin had higher unadjusted rates of death and/or re-MI and CHF than patients on prior ASA only. Conclusions ACS patients on prior warfarin are a high-risk population, yet they receive less guideline-recommended therapies and have higher unadjusted adverse event rates during their index hospitalization. With the increasing use of oral anticoagulants, clinical trials are needed to guide the optimal management of these ACS patients.

PFO and Stroke

Patent foramen ovale (PFO) is a frequent finding on echocardiography and occurs in over 25% of the population. In young patients with cryptogenic stroke, the frequency is much higher suggesting paradoxical embolization may be responsible for the clinical events. There are conflicting data from studies examining the association between PFO and stroke. The combination of atrial septal aneurysm and PFO, and PFO size and severity of right-to-left shunt may add additional risk but again the data are insufficient for definite conclusions. Available information suggests no difference in subsequent stroke in patients with PFO treated with aspirin or warfarin for secondary prevention. Endovascular closure is technically feasible, but not without the possibility of periprocedural complications. Comparison of medical and endovascular closure of PFOs in patients with stroke is ongoing in 2 major randomized trials.

Aspirin plus clopidogrel is similarly efficacious to aspirin plus warfarin for secondary prevention following acute coronary syndromes,

Aspirin plus clopidogrel is similarly efficacious to aspirin plus warfarin for secondary prevention following acute coronary syndromes,

Secondary Prevention of Venous Thromboembolic Events in Patients With Active Cancer: Enoxaparin Alone Versus Initial Enoxaparin Followed by Warfarin for a 180-Day Period

This study evaluated enoxaparin alone versus initial enoxaparin followed by warfarin in secondary prevention of venous thromboembolic events in adults with active malignancy. Cancer patients (n = 122) with acute symptomatic venous thromboembolic events were randomly allocated to receive subcutaneous enoxaparin 1.0 mg/kg every 12 hours for 5 days, followed by 1.0 mg/kg daily (group 1a) or 1.5 mg/kg daily (group 1b) for 175 days, or subcutaneous enoxaparin 1.0 mg/kg every 12 hours for at least 5 days and until a stable international normalized ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day 180 (group 2). There were no significant differences in major and minor bleeding rates between treatment groups. No bleeding events were intracranial or fatal. Enoxaparin treatment was feasible, generally well tolerated, and effective for a 180-day period in the secondary prevention of venous thromboembolic events in patients with active malignancy.

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?—Reply

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?—Reply

Comparison of low-molecular-weight heparin and warfarin for secondary prevention of venous thromboembolism in patients with cancer. A randomized controlled study

Comparison of low-molecular-weight heparin and warfarin for secondary prevention of venous thromboembolism in patients with cancer. A randomized controlled study