scholarly journals Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

2014 ◽  
Vol 39 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Qinghua Zhang ◽  
Chao Wang ◽  
Maoyong Zheng ◽  
Yanxia Li ◽  
Jincun Li ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Secondary Prevention ◽  
Major Bleeding ◽  
Hemorrhagic Stroke ◽  
Stroke Recurrence ◽  
Short Term ◽  
Bleeding Events ◽  
Vascular Events ◽  
Major Bleeding Events

Background: Antiplatelet agents are the mainstay for secondary prevention of non-cardioembolic stroke. This systematic review examined the safety and efficacy of short-, middle-, and long-term aspirin in combination with clopidogrel as secondary prevention of stroke or transient ischemic attack (TIA) of presumed arterial origin. Methods: PubMed, EmBase, and CENTRAL were searched up to May 2014. Randomized controlled trials (RCTs) that compared aspirin plus clopidogrel versus aspirin or clopidogrel as secondary prevention of stroke or TIA of arterial origin were included. The analyses were stratified into short-term (≤3 months), middle-term (>3 months and <1 year), and long-term (≥1 year). Outcomes were compared using risk ratio (RR) and 95% confidence interval (95% CI). Results: Eight RCTs (20,728 patients) were included in the overall analysis. Compared with aspirin or clopidogrel alone, the complete analysis of all the data indicated that the combination therapy significantly reduced the risk of stroke recurrence (RR, 0.82; 95% CI 0.70-0.96, p = 0.01) and major vascular events (RR, 0.84; 95% CI 0.73-0.96, p < 0.01). But the risk of hemorrhagic stroke (RR, 1.59; 95% CI 1.08-2.33, p = 0.02) and major bleeding (RR, 1.83; 95% CI 1.37-2.45, p < 0.01) was increased. No RCT studied middle-term combination therapy. The analyses were therefore stratified into only two subgroups, short- and long-term treatment. Stratified analysis of short-term treatment showed that relative to monotherapy, the drug combination reduced the risk of stroke recurrence (RR, 0.69; 95% CI 0.59-0.81, p < 0.01) and did not increase the risk of hemorrhagic stroke (RR, 1.23; 95% CI 0.50-3.04, p = 0.65) and major bleeding events (RR, 2.17; 95% CI 0.18-25.71, p = 0.54). Short-term combination therapy was associated with a significantly lower risk of major vascular events (RR, 0.70; 95% CI 0.69 to 0.82, p < 0.01). Stratified analysis of long-term treatment revealed that the combination treatment did not decrease the risk of stroke recurrence (RR, 0.92; 95% CI 0.83-1.03, p = 0.15), but was associated with a significantly higher risk of hemorrhagic stroke (RR, 1.67; 95% CI 1.10-2.56, p = 0.02) and major bleeding events (RR, 1.90; 95% CI 1.46-2.48, p < 0.01). Long-term combination therapy failed to reduce the risk of major vascular events (RR, 0.92; 95% CI 0.84-1.03, p = 0.09). Conclusions: Compared with monotherapy, short-term aspirin in combination with clopidogrel is more effective as secondary prevention of stroke or TIA without increasing the risk of hemorrhagic stroke and major bleeding events. Long-term combination therapy does not reduce the risk of stroke recurrence, and is associated with increased major bleeding events. The clinical applicability of the findings of this systematic review, however, needs to be confirmed in future clinical trials.

scholarly journals Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Faizan Khan ◽  
Miriam Kimpton ◽  
Tobias Tritschler ◽  
Grégoire Le Gal ◽  
Brian Hutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

scholarly journals Antiplatelet Therapy After Noncardioembolic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (7) ◽  
pp. 1812-1818 ◽  
Author(s):  
Jacoba P. Greving ◽  
Hans-Christoph Diener ◽  
Johannes B. Reitsma ◽  
Philip M. Bath ◽  
László Csiba ◽  
...  
Keyword(s):  
Secondary Prevention ◽  
Major Bleeding ◽  
Transient Ischemic Attack ◽  
Clinical Benefit ◽  
Antiplatelet Agents ◽  
Vascular Events ◽  
Subgroup Analyses ◽  
Ischemic Attack ◽  
Net Clinical Benefit

Background and Purpose— We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients’ demographic and clinical characteristics. Methods— We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results— Aspirin/dipyridamole combination (RR NMA-adj , 0.83; 95% CI, 0.74–0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RR NMA-adj , 0.88; 95% CI, 0.78–0.98), and aspirin/clopidogrel combination (RR NMA-adj , 0.83; 95% CI, 0.71–0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RR NMA-adj , 0.99; 95% CI, 0.93–1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RR NMA-adj , 3.9 versus 1.7). Conclusions— Results favor clopidogrel and aspirin/dipyridamole combination for long-term secondary prevention after noncardioembolic stroke or transient ischemic attack, regardless of patient characteristics. Aspirin/clopidogrel combination was associated with a significantly higher risk of major bleeding compared with other antiplatelet regimens.

Antithrombotic Treatment and Outcomes of Splanchnic Vein Thrombosis in an International Prospective Registry: Results of 2-Year Follow-up

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 592-592
Author(s):  
Walter Ageno ◽  
Nicoletta Riva ◽  
Sam Schulman ◽  
Jan Beyer-Westendorf ◽  
Soo-Mee Bang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Events ◽  
Primary Analysis ◽  
Vascular Events ◽  
Vein Thrombosis ◽  
Cirrhotic Patients

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study

2017 ◽  
Vol 44 (04) ◽  
pp. 348-352 ◽  
Author(s):  
Reinhard Raggam ◽  
Franz Hafner ◽  
Alexander Avian ◽  
Gerald Hackl ◽  
Gerhard Cvirn ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Prospective Evaluation ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

A Systematic Review Evaluating the Effects of Treatment Duration on Bleeding Due to Factor-specific Oral Anticoagulant Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3417-3417
Author(s):  
Natalie Chan ◽  
Chantal Li ◽  
Keith K. Lau ◽  
Anthony K.C. Chan ◽  
Howard H.W. Chan
Keyword(s):  
Major Bleeding ◽  
Steering Committee ◽  
Bleeding Complications ◽  
Duration Of Treatment ◽  
Bleeding Events ◽  
Major Bleed ◽  
Major Bleeding Events ◽  
Anticoagulant Prophylaxis ◽  
Definition Of

Abstract Abstract 3417 Introduction: Oral factor-specific anticoagulants have been a highlight of thrombosis research over the past few years. Apart from predictable pharmacokinetic properties, multiple randomized control trials have demonstrated that they are non-inferior to other traditional anticoagulants in terms of therapeutic activity. These new anticoagulants seem to have a lower bleeding risk when compared with conventional therapy offering the potential for safer therapy over longer durations of treatment. Objectives: This is a systematic review to determine (1) the homogeneity of bleeding-classifications among the randomized trials, and (2) the relationship between bleeding event and treatment duration. Methods: Ovid MEDLINE databases from 1946 to May 2012 were searched using apixaban, betrixaban, dabigatran, edoxaban, or rivaroxaban as keywords. Reviews, case reports, subgroup analyses, ex-vivo, in-vitro, or animal studies were excluded; only randomized controlled trials were included in the final review. Data regarding the study design, study setting, therapeutic intervention, bleeding classification and bleeding outcomes were extracted. The studies were categorized into two major groups: (1) non-operative studies for the treatment of patients with atrial fibrillation, acute coronary syndrome, deep vein thrombosis, or pulmonary embolism, (2) perioperative studies evaluating patients after knee or hip replacement. Criteria in the Cochrane guidelines were used to define the risk of bias. The definitions of bleeding classification were assessed for homogeneity. Results from studies which had homogeneous bleeding classifications were pooled and the correlation between bleeding events and the duration of treatment was analyzed using the correlation coefficient (R2value). For each drug, the standard dose(s) that were commonly used in the latest clinical trials were chosen to be included in the final analysis. Results: 522 publications were found in the primary search. Two independent investigators identified 43 eligible trials. In general, bleeding events were classified into major and non-major bleeding, with clinically relevant non-major bleeding as a subset of non-major bleeding in newer trials. The definition of major bleeding was relatively homogenous for both non-operative and perioperative studies, although the classification of non-major bleeding events was more heterogeneous. Given that major bleeding events were consistently reported in most studies and the criteria of the classification are comparable, the rate of major bleeding was pooled to evaluate against the duration of treatment. The R2 value was 0.784 for non-operative studies, suggesting that the rate of major bleeding events was moderately associated with the duration of treatment with an event rate of 2.6 bleeds per year. In contrast, the R2value was −0.398 for perioperative studies, suggesting that the duration of treatment was not a determining factor for the rate of major bleeding events in the perioperative population. Conclusion: Although the classification of bleeding events is evolving, the definition of major bleeding has been consistent enough among studies allowing direct comparison and pooled analysis. For patients with thromboembolisms requiring long term anticoagulant therapy at full therapeutic dose for more than 12 months, the literature showed that the risk of having a major bleed was 2.6% per year. Therefore, the decision for long term anticoagulant use should be balanced against the ongoing thrombosis risk. After the acute phase when patients have lower prothrombotic risk, dose reduction should be considered to reduce the risk of bleeding complications. On the other hand, for patients requiring anticoagulant prophylaxis after major surgery, the risk of having major bleed in the immediate post-operative period is not completely dependent on the duration of treatment due to other confounding factors such as the surgical intervention itself. If certain patients are at a high risk of thrombosis after surgery, extended duration of anticoagulant prophylaxis can be safely considered. The results of this systemic review should help physicians and future investigators reducing the bleeding complications associated with new oral factor-specific anticoagulants, thereby improving their therapeutic and prophylactic values. Disclosures: Chan: BMS: Chair of Adjudication Committee, Chair of Adjudication Committee Other; Aventis: Chair of Steering Committee, Chair of Steering Committee Other; Boehringer ingelheim: Member of DMSB for Clinical Trial, Member of DMSB for Clinical Trial Other; Bayer: Consultancy.

scholarly journals What Can We Learn from the Past by Means of Very Long-Term Follow-Up after Aortic Valve Replacement?

2021 ◽  
Vol 10 (17) ◽  
pp. 3925
Author(s):  
Ben Swinkels ◽  
Jurriën ten Berg ◽  
Johannes Kelder ◽  
Freddy Vermeulen ◽  
Wim Jan van Boven ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Major Bleeding ◽  
Left Ventricular ◽  
Bleeding Events ◽  
Term Survival ◽  
Long Term Survival ◽  
Major Bleeding Events

Background: Studies on very long-term outcomes after aortic valve replacement are sparse. Methods: In this retrospective cohort study, long-term outcomes during 25.1 ± 2.8 years of follow-up were determined in 673 patients who underwent aortic valve replacement with or without concomitant coronary artery bypass surgery for severe aortic stenosis and/or regurgitation. Independent predictors of decreased long-term survival were determined. Cumulative incidence rates of major adverse events in patients with a mechanical versus those with a biologic prosthesis were assessed, as well as of major bleeding events in patients with a mechanical prosthesis under the age of 60 versus those above the age of 60. Results: Impaired left ventricular function, severe prosthesis–patient mismatch, and increased aortic cross-clamp time were independent predictors of decreased long-term survival. Left ventricular hypertrophy, a mechanical or biologic prosthesis, increased cardiopulmonary bypass time, new-onset postoperative atrial fibrillation, and the presence of symptoms did not independently predict decreased long-term survival. The risk of major bleeding events was higher in patients with a mechanical in comparison with those with a biologic prosthesis. Younger age (under 60 years) did not protect patients with a mechanical prosthesis against major bleeding events. Conclusions: Very long-term outcome data are invaluable for careful decision-making on aortic valve replacement.

scholarly journals Major Bleeding Events Are Stronger Predictors of Long-Term Mortality Than Coronary Events in Secondary Prevention Therapy for Ischaemic Heart Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Shigetaka Kageyama ◽  
Koichiro Murata ◽  
Ryuzo Nawada ◽  
Tomoya Onodera ◽  
Yuichiro Maekawa
Keyword(s):  
Blood Pressure ◽  
Heart Disease ◽  
Secondary Prevention ◽  
Major Bleeding ◽  
Coronary Event ◽  
Bleeding Events ◽  
Coronary Events ◽  
Long Term Mortality

Background. Secondary prevention of ischaemic heart disease (IHD) is an important aspect of healthcare. To improve the prognosis of and control risk factors for IHD patients, we created a unique referral system called the Shizuoka IHD patient registry. Methods. From 2009 to 2013, we enrolled 1240 patients; they participated in follow-up until 2018. The risk factor target values were as follows: low-density-lipoprotein cholesterol, <100 mg/dl; glycated haemoglobin of diabetes patients, <7%; systolic blood pressure, <130 mmHg; and diastolic blood pressure, <80 mmHg (mean follow-up interval, 2001 ± 794 days). The cumulative incidence rates were 10.8% for all-cause death (cardiac death, 1.5%), 15.7% for coronary events, and 2.6% for major bleeding. Patients were separated into the major bleeding group (n = 32), coronary event group (n = 195), and event-free group (n = 1013) without overlapping. Results. We observed significant differences in age, rate antithrombotic drug use, and mortality. A Kaplan–Meier analysis of all-cause death showed significant differences between the event-free and major bleeding groups ( P = 0.002 ) and between the coronary event and major bleeding groups ( P = 0.026 ); there was no significant difference between the event-free and coronary event groups. Conclusion. Major bleeding events were stronger predictors of long-term mortality than coronary events during the long-term follow-up of stable IHD.

scholarly journals MO732HD-PATIENTS WITH ATRIAL FIBRILLATION TREATED ADEQUATELY AND SAFE WITH DOAC BY INDIVIDUAL DOSING USING ROUTINE ANTI-XA DRUG-EFFECT MONITORING: LONG-TERM CLINICAL PRACTICE DATA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Karl August Brensing ◽  
Peter Raab ◽  
Peter Heidkamp ◽  
Uwe Pöge
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Drug Effect ◽  
High Dose ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Vascular Events ◽  
Effect Monitoring

Abstract Background and Aims Hemodialysis (HD) patients (Pts) with nonvalvular atrial fibrillation (AF) on anti-vitamin-K oral anticoagulation (VK-OAC) are at high risk for cardio-vascular events, major bleeding and rapid vascular/valvular calcification. Thus, current VK-OAC is debated since prospective studies are missing, but all direct oral anticoagulation drugs (DOACs) are not labeled for ESRD. We studied the clinical feasibility of long-term DOAC treatment in HD-pts using individual dosing by regular anticoagulant drug-effect monitoring. Method We analysed 9 HD-patients with AF (median age 77 yrs; range=R: 59-86; 7 Male) on DOAC therapy for at least 6 months (n=1 rivaroxaban=Riva, n=8 apixaban=Apix) initiated by cardiologist with patients informed consent with lower dose as in CKD-4 under regular (weekly) anti-Xa drug-effect monitoring (prior HD) using available routine laboratory test validated for low-molecular heparin: Target trough range (12-24h after drug) was 0.1-1.0 U/ml (=prophylactic to therapeutic anti-Xa levels; test range &lt;0.1, &gt;1.6 U/ml). Bleeding caused drug stop/reduction until anti-Xa control. Results Median study time was 14 months (R: 6-24). We analysed 310 anti-Xa levels on Apix and 83 levels on Riva. After dose adjustment finally 2 Apix-Pts (22%) received full CKD-4 dose (35 mg/week=wk) and 7 patients (78%) had median dose of 10 mg/wk (10-27 mg; 6x Apix) or 40 mg/wk Riva, i.e. 29% and 38% of usual CKD-4 dose. Two Pts with higher dose had clinical reasons: short-bowl-syndrome (less resorption) or high grade (3-4) left atrial sludge (therapeutic goal). Overall, median anti-Xa level was 0.47 U/ml (R: &lt;0.1-&gt;1.6) and 80% were in center-accepted targets: 0.1-1.2 U/ml. Lower dose Pts had higher in-target-rate (83%) than the 2 high dose Pts (70%) by more exceeding the upper limit. During our study we saw no cerebral/systemic thrombo-embolic event or major bleeding, but 2 pts had epistaxis (need out-patient intervention), 1x persistent macrohematuria (need catheterization) and 3 pts. had multiple subcutaneous hematoma, none needed event-related transfusion. We saw two non-cardiovascular deaths (22%; 2/9): 1x pneumonic sepsis, 1x advanced cancer. Conclusion We provide new clinical feasibility data on long-term DOACs therapy in HD-patients. Since DOACs are not labelled for ESRD we recommend strict indication plus regular anti-Xa drug-effect monitoring for adequate individual dosing. Our data support initial doses as for CKD-4 but applied only on HD-free days (4x/wk; =57% of usual) and adjustment in steady-state (1-2 wks): final individual doses were increased up to 100% in some patients, but mostly were reduced to 30-40% of usual CKD-4 doses. Overall, this individual dosing approach for DOACs provided adequate anti-Xa levels to prevent thrombo-embolic as well as major bleeding events. This initial data need to be confirmed in larger studies to improve evidence-based management of HD-patients with nonvalvular AF.

scholarly journals Intermediate vs Standard-dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to ICU: Ninety-day Results from the INSPIRATION Trial

2021 ◽  
Author(s):  
Behnood Bikdeli ◽  
Azita H Talasaz ◽  
Farid Rashidi ◽  
Hooman Bakhshandeh ◽  
Farnaz Rafiee ◽  
...  
Keyword(s):  
Hospital Discharge ◽  
Major Bleeding ◽  
Arterial Thrombosis ◽  
Dose Group ◽  
Standard Dose ◽  
Controlled Trial ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
Prophylactic Anticoagulation ◽  
Intermediate Dose

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

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