Indication For Long-term Anticoagulation Research Articles

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism

IntroductionApproximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. MethodsThis is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. ResultsOverall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. ConclusionsMost patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Risk of Recurrent Venous Thromboembolism in Patients with Acute Isolated Subsegmental Pulmonary Embolism - a Single Center Chart Review

Introduction: The incidence of pulmonary embolism (PE) has been increasing, but its case-fatality rate is decreasing over time, suggesting overdiagnosis, a lesser severity of the illness and/or improvements in treatment strategies. Approximately 10-14% of all diagnosed PE are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE), managed with or without anticoagulant therapy, remains poorly understood. Methods and analysis: This is an observational, retrospective cohort study of adult patients diagnosed with an acute isolated SSPE (single or multiple) at The Ottawa Hospital, Ontario, Canada, from June 01, 2019, to August 31, 2022. Data on diagnosis and follow-up were collected through a retrospective review of the medical records. Among inclusion criteria, no selection was made on provoking factors or on presence/absence of symptoms at presentation. We excluded those patients with concomitant diagnosis of deep vein thrombosis (DVT) who were started on anticoagulation and those who had an indication for long-term anticoagulation at the time of SSPE diagnosis (e.g. atrial fibrillation). The primary outcome was recurrent VTE events other than SSPE, occurring after the diagnosis among patients managed without anticoagulation, and after treatment initiation among those treated with anticoagulation. Results: Overall, 120 patients with a diagnosis of acute SSPE were included in the analysis. The mean age of the participants was 59 +/- 3 years, 47% were women, the mean body weight was 76 +/- 4 kg, and 35% of them had active cancer. Seventy-nine patients (66%) were treated with anticoagulation, whereas 41 patients (34%) were not. The most frequent treatment was direct oral anticoagulant, being used in 64/79 patients (81%), whereas 15/79 patients (19%) received low molecular weight heparin. Most patients were treated for 3-6 months. Twenty-one (28%) of treated patients continued long-term anticoagulation for secondary prevention. Individuals with active cancer at time of SSPE diagnosis were 32/79 (41%) and 10/41 (24%), respectively among treated and not treated patients. Overall, duration of follow-up was 452 +/- 77 days; 7 patients were lost to follow-up. Recurrent VTE events occurred in 7/113 (6.2%) patients: 5/75 (6.7%, 95% CI 2.2 to 14.9) of them were diagnosed in the treatment group (2 occurred while on anticoagulation and 3 after discontinuation of treatment) and the other 2/38 (5.3%, 95% CI 0.6 to 17.8) were detected among patients managed without anticoagulation. Recurrences were mostly represented by more proximal PEs (5 patients), one patient had an upper extremity DVT and the other one was diagnosed with both DVT and proximal PE. Conclusions: In our retrospective cohort study, most patients diagnosed with an acute SSPE received anticoagulation. The prevalence of recurrent thromboembolic events detected over more than a year follow-up was relatively high, with 6.7% and 5.3%, respectively, among patients treated with anticoagulation and those managed without anticoagulation. Further data are needed to better understand the natural history of this thrombotic complication and to identify the right patients who would benefit from anticoagulation.

Feasibility, effectiveness, and safety of edoxaban administration through percutaneous endoscopic gastrostomy: 12-months follow up of the ORIGAMI study.

Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. ORIGAMI was a prospective, single-arm, observational study (NCT04271293). Patients with PEG and an indication for long-term anticoagulation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. The primary endpoint was the composite of cardio-embolic events consisting of ischemic stroke, systemic embolism, or symptomatic deep venous thrombosis/pulmonary embolism (DVT/PE). Secondary endpoints were the number of bleeding events and edoxaban plasma concentrations at steady state. We here report the 12-month results. A total of 12 patients were enrolled. The main indication for PEG implantation was amyotrophic lateral sclerosis (10/12). The primary endpoint of cardio-embolic events did not occur in any patients at 12 months. All patients were in the therapeutic range of steady-state edoxaban plasma levels. Three minor bleedings were observed, while no major bleedings occurred during the observational period. A total of five patients died. All deaths were from non-cardiovascular causes and were consistent with the natural history of the pre-existing severe disease. Our study suggests that edoxaban administration via PEG is feasible and appears safe and effective in fragile, comorbid patients, resulting in therapeutic plasma concentrations of edoxaban. [ClinicalTrials.gov], identifier [NCT04271293].

From the Editor’s Desk…

From the Editor’s Desk…

Abstract 12210: Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation vs Interruption of Peri-Procedural Anticoagulation: A Meta-Analysis

Introduction: Approximately 33% of patients undergoing transcatheter aortic valve replacement (TAVR) have an indication for long-term anticoagulation. In clinical routine, anticoagulation is often discontinued 2 to 4 days before TAVR. The purpose of this meta-analysis was to compare the safety and efficacy of TAVR in patients with per-procedural continuation vs interruption of anticoagulation. Methods: An electronic search was performed using PubMed and Ovid Medline from inception to May 2022. The primary outcome of interest was life-threatening or major bleeding. The secondary outcomes were all-cause mortality, stroke, vascular complications, need for blood transfusion, and closure device failure. Results: Three observational studies were included in our final analysis which consisted of 2,286 patients, with anticoagulation being continued in 1,069 patients and interrupted in 1,217 patients. Although, there was no significant difference in our primary outcome of life-threatening or major bleeding between both groups, there was a trend toward decreased risk of bleeding in patients who were continued on anticoagulation (RR: 0.81; CI: 0.65 to 1.0; I 2 : 0%, p=0.05). There was a significantly lower risk of stroke (RR: 0.55; CI: 0.35 to 0.88; I 2 : 0%, p=0.01) and need for blood transfusion (RR: 0.72; CI: 0.59 to 0.87; I 2 : 0%, p<0.01) in patients who were continued on anticoagulation as compared to those in whom anticoagulation was interrupted. There was no significant difference in the all-cause mortality (RR: 0.76; CI: 0.49 to 1.19; I 2 : 10%, p=0.24), major vascular complications (RR: 0.86; CI: 0.68 to 1.09; I 2 : 0%, p=0.22), or closure device failure (RR: 0.90; CI: 0.51 to 1.59; I 2 : 0%, p=0.72) between both the cohorts. Conclusions: In a patient undergoing TAVR who requires long-term anticoagulation, continuing anticoagulation is superior to interrupting anticoagulation in reducing the risk of stroke without any increase in life-threatening or major bleeding.

IS THE PATENT FORAMEN OVALE AN INNOCENT BYSTANDER OR THE REAL CULPRIT? THE MILLION-DOLLAR QUESTION

IS THE PATENT FORAMEN OVALE AN INNOCENT BYSTANDER OR THE REAL CULPRIT? THE MILLION-DOLLAR QUESTION

Incidence and factors predictive of recurrent thrombosis in people with non-cirrhotic portal vein thrombosis

Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in people with NC-SVT without an indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. This is a multicentre, retrospective observational study evaluating risk factors for RT in 64 people with NC-SVT of idiopathic/local factor aetiology. In a subgroup of 48 individuals, the potential value of additional thrombophilic parameters to predict RT was analysed. Findings were validated in 70 individuals with idiopathic/local factor NC-SVT. Of the 64 participants in the training cohort, 17 (26%) presented splanchnic and/or extrasplanchnic RT (overall-RT) during follow-up (cumulative incidence: 2, 10, 19, and 34% at 1, 2, 5, and 10 years, respectively). In addition, 53% of people with splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 people with an additional comprehensive thrombophilic study, factor VIII ≥150% was the only independent factor predicting overall-RT (hazard ratio 7.10, 95% CI 2.17-23.17, p <0.01). In the validation cohort, 19 individuals (27%) presented overall-RT, and it was also independently predicted by factor VIII >150% (hazard ratio 3.71, 95% CI 1.31-10.5, p <0.01). The predictive value of factor VIII was confirmed in both people with idiopathic/local factor aetiology associated NC-SVT. People with idiopathic/local factor NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥150% may help identify individuals at high risk of overall-RT who could benefit from long-term anticoagulation. People with idiopathic/isolated local factor non-cirrhotic portal vein thrombosis were previously thought to be at minimal risk of re-thrombosis and therefore did not receive scheduled follow-up. The results of this study are of special interest for hepatologists treating people with non-cirrhotic splanchnic thrombosis, as they show a 25% incidence of re-thrombosis and support the close follow-up of people with factor VIII >150% to ensure the early identification of new thrombotic events.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. URL: https://www. gov. Unique identifier: NCT03284827.

When and How to Combine Antiplatelet and Anticoagulant Drugs?

Antiplatelet and anticoagulant drugs work at different places in the coagulation system. Antiplatelet drugs are usually indicated in patients with atherosclerosis. Anticoagulant drugs are mostly used in patients with atrial fibrillation, venous thromboembolism, or technical heart valves. In some clinical situations, combination of antiplatelet and anticoagulant therapy can be indicated. The most recent situations are a more intensive antithrombotic therapy for risk reduction in patients with atherosclerosis and temporary addition of antiplatelet drugs in patients with indication for long-term anticoagulation. Temporary combination of antiplatelet and anticoagulant drugs is usually necessary after coronary intervention in patients with atrial fibrillation. In patients with high-risk atherosclerosis, the combination of low-dose rivaroxaban and aspirin reduces major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death) and major adverse limb events. But every combination of antiplatelet and antithrombotic drugs can increase bleeding risk. Therefore, a careful assessment of thrombotic versus bleeding risk is necessary for each patient.

Abstract 11055: Length of Anticoagulation Treatment in Provoked VTE - Lessons from the Maqi 2 Collaborative

Introduction: Anticoagulation (AC) with warfarin or direct oral anticoagulants (DOAC) is the core of VTE treatment. Due to lower risk of VTE recurrence, American College of Chest Physicians (ACCP) recommends three months AC in patients with provoked VTE and without other indication for long-term AC. We aimed to assess how closely “real world” practice followed guideline recommendations. Hypothesis: We hypothesize most patients taking warfarin or DOAC for provoked VTE receive no more than three months AC. Patients who get prolonged AC are more likely to be taking DOAC than warfarin. Methods: We identified patients who initiated warfarin or DOAC from a six center AC clinic registry between 2008-20. Provoked VTE was defined as VTE after a transient risk factor: surgery, lower extremity cast/immobilization, childbirth, or OCPs. AC duration was categorized as &lt;80, 80-120, or &gt;120 days. Appropriate treatment window was defined as 80-120 days to adjust for variability in clinic scheduling. Median AC length for DOAC vs. warfarin was compared with a two-sample test. Prevalence of extended AC was compared using chi-square test. Variables increasing risk of extended AC were analyzed with logistic regression, adjusted for baseline demographic and clinical characteristics. Results: At six centers, we identified 488 patients with provoked VTE on warfarin and 302 on DOAC. Average AC length was 137 days for warfarin and 180 days for DOAC (p&lt;0.0001). 266 (54.5%) patients on warfarin and 215 (71.2%) on DOAC got &gt;120 days of AC (p&lt;0.001). Variables increasing risk of &gt;120 days AC include recurrent VTE (OR 2.11; CI 1.34,3.32), prior MI (OR 4.09; CI 1.37,12.2), and DOAC use (OR 2.34; CI 1.69, 3.23) (Figure 1). Conclusions: In this multi-center analysis, most patients receive AC longer than guideline-recommended. DOAC use, recurrent VTE, and prior MI are associated with prolonged AC. Understanding the relationship between prior MI and AC duration in provoked VTE warrants future investigation.

Abstract 10242: Single versus Dual Antiplatelet Post Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis

Introduction: Perioperative use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) remains controversial. This meta-analysis compares the safety and efficacy of single anti-antiplatelet therapy (SAPT) versus DAPT after TAVR in patients with no indications for long-term anticoagulation. Hypothesis: The use of SAPT is safe and efficacious in TAVR patients. Methods: Electronic databases were queried for randomized controlled trials (RCTs) and observational studies matching the inclusion criteria. The safety endpoints included bleeding and major vascular complications. The efficacy outcomes included myocardial infarction (MI), stroke, short and long-term all-cause mortality. The ratio risk ratio (RR) with 95% confidence interval (CI) was computed using a random-effect model. Results: A total of 4 RCTs and 2 observational studies (n=1,417) were included in the final analysis. There were decreased rates of bleeding (life-threatening or major) (RR: 0.44; CI: 0.31-0.63) with aspirin only therapy. However, there was no difference of MI (RR: 0.73; CI: 0.28-1.87), stroke (RR: 0.92; CI: 0.55-1.54), major vascular complications (RR: 0.61; CI: 0.35-1.07), short-term mortality (&gt;30 days) (RR: 0.82; CI: 0.45-1.49), and long-term mortality (&gt;30 days) (RR: 1.13; CI: 0.73-1.76). Conclusions: This analysis showed lower rates of bleeding and composite of bleeding/thromboembolic events with aspirin only compared to dual antiplatelet amongst patients that underwent TAVR for aortic stenosis.

Tromboembolismo pulmonar

Pulmonary thromboembolism is a potentially serious disease, secondary to pulmonary arterial obstruction by thrombotic material, which alters ventilation-perfusion balance with secondary hypoxaemia, and entails a sudden overload for the right ventricle that can result in life-threatening haemodynamic failure. Management should be based on stratifying the severity of the clinical picture to then undertake a specific diagnostic process, using algorithms based on the patient's clinical characteristics, laboratory tests (especially D-dimer and markers of myocardial damage) and imaging techniques (echocardiography, CT angiography, etc.). Treatment should be initiated early, and consists on haemodynamic and respiratory support measures, along with treatment with fibrinolytics or anticoagulants depending on the patient's clinical situation. Finally, the indication for long-term anticoagulation should be assessed on individual basis taking risk/benefit into account.

Comparison of Bleeding Risk between Rivaroxaban and Apixaban: a Pilot Feasibility Study

Introduction: The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have simplified the treatment of acute venous thromboembolism (VTE). Phase III randomized controlled trials demonstrated each DOAC to have similar or better safety and efficacy profiles to vitamin K antagonists, while network meta-analyses suggest that apixaban might be associated with fewer bleeding events than rivaroxaban. Trial limitations and lack of direct comparison between these agents make it impossible to know which DOAC confers the best risk-benefit ratio. The COBRRA (COmparison of Bleeding Risk between Rivaroxaban and Apixaban) pilot feasibility study (NCT02559856) was designed to determine if it is feasible to conduct a large randomized multicenter trial comparing apixaban to rivaroxaban for the treatment of acute VTE.Methods: Adult patients with symptomatic acute VTE were eligible for randomization to apixaban or rivaroxaban in an open-label fashion. The exclusion criteria were: had received >72 hours of therapeutic anticoagulation; creatinine clearance <30 ml/min; another indication for long term anticoagulation; weight >120 Kg; known Child-Pugh B or C liver disease; active bleeding; active malignancy; pregnancy/breastfeeding; and use of contraindicated medications. Patients were followed on anticoagulation for 3 or 6 months.The pilot trial was conducted in 4 Canadian centers that are part of the CanVECTOR network. Two sites are established Thrombosis research centers and the other 2 sites are emerging research centers with minimal established research infrastructure. The primary outcome was recruitment of at least 2 patients per month per site over a mean of 6 months recruitment. Secondary outcomes included major bleeding, clinically relevant non-major bleeding, and minor bleeding events; recurrent VTE; VTE related deaths; and all-cause mortality.Results: Seventy-two patients were enrolled with mean recruitment of 4 patients per month at experienced sites and 2 patients per month at new sites. Baseline clinical characteristics are available in Table 1. Thirty-four patients were randomized to apixaban with mean age 58 years; 37 patients were randomized to rivaroxaban and had mean age of 63 years.Follow up visits are ongoing at three participating sites and results will be available in October 2017. No patients have been lost to follow up.Conclusions: This pilot trial is the first direct comparison of rivaroxaban and apixaban for acute VTE treatment. Recruitment targets were met hence we demonstrated feasibility of the main trial. The sample size of the full study is estimated to be 2760 patients. With recruitment rates similar to those observed in this pilot study, we would need at least 10 experienced centers and 8 emerging sites to ensure enrolment is completed over 4 years. Secondary outcome reporting will be available for the 59th ASH Annual Meeting. [Display omitted] DisclosuresCastellucci:BMS: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria; Boehringer-Ingelheim: Honoraria; Pfizer: Honoraria. Le Gal:Bayer: Honoraria; BMS: Honoraria.

Safety and Efficacy of Different Antithrombotic Strategies after Transcatheter Aortic Valve Implantation: A Network Meta-Analysis.

The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) remains uncertain. We compared efficacy and safety of various antiplatelet and anticoagulant approaches after TAVI by a network meta-analysis. A total of 14 studies (both observational and randomized) were considered, with 24,119 patients included. Primary safety endpoint was the incidence of any bleeding complications during follow-up. Secondary safety endpoint was major bleeding. Efficacy endpoints were stroke, myocardial infarction, and cardiovascular mortality. A frequentist network meta-analysis was conducted with a random-effects model. The following strategies were compared: dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), oral anticoagulation (OAC), and OAC + SAPT. The mean follow-up was 15 months. In comparison to DAPT, SAPT was associated with a 44% risk reduction of any bleeding (odds ratio [OR]: 0.56 [95% confidence interval, CI: 0.39-0.80]). SAPT was ranked as the safest strategy for the prevention of any bleeding (p-score: 0.704), followed by OAC alone (p-score: 0.476) and DAPT (p-score: 0.437). Consistent results were observed for major bleeding. The incidence of cardiovascular death and secondary ischemic endpoints did not differ among the tested antithrombotic approaches. In patients with indication for long-term anticoagulation, OAC alone showed similar rates of stroke (OR: 0.92 [95% CI: 0.41-2.05], p = 0.83) and reduced occurrence of any bleeding (OR: 0.49 [95% CI: 0.37-0.66], p < 0.01) versus OAC + SAPT. The present network meta-analysis supports after TAVI the use of SAPT in patients without indication for OAC and OAC alone in those needing long-term anticoagulation.

Antiplatelet therapy after transcatheter aortic valve implantation: a systematic review and meta-analysis.

The aim of this study was to compare antithrombotic regimens after transcatheter aortic valve implantation (TAVI) in patients without an indication for long-term anticoagulation. TAVI is a safe and effective approach for patients with symptomatic severe aortic stenosis and an intermediate-to-high surgical risk. Nevertheless, the antithrombotic regimen after procedure remains controversial. We systematically searched PubMed, Embase and Cochrane databases for interventional studies comparing single antiplatelet therapy with double antiplatelet therapy after TAVI. A meta-analysis was carried out to compare thrombotic and bleeding events between both strategies. Four randomized clinical trials were included comprising a total of 1085 patients. Our meta-analysis revealed a higher odds ratio (OR) of major bleeding events (pooled OR 2.45, 95% confidence interval (CI) 1.29-4.67; P < 0.01; I2 = 0%) and minor bleeding (pooled OR 1.73, 95% CI 1.12-2.66; P = 0.01; I2 = 0%) for the double antiplatelet therapy group compared with the single antiplatelet therapy group. There was no difference between groups in the risk of stroke (pooled OR 1.04, 95% CI 0.58-1.86; P = 0.91; I2 = 0%), myocardial infarction (pooled OR 2.10, 95% CI 0.75-5.84; P = 0.16, I2 = 0%) and all-cause mortality (pooled OR 1.07, 95% CI 0.63-1.86; P = 0.08; I2 = 0%) after TAVI. Our pooled analysis suggests that for patients who underwent TAVI, double antiplatelet therapy compared with single antiplatelet therapy alone increased the risk of bleeding without reducing mortality and ischaemic events.

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

BackgroundThe effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied.MethodsIn a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non–procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non–procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non–procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.ResultsA total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non–procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial.ConclusionsAmong patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.)

Patent foramen ovale and stroke: current evidence and treatment options.

Recent data have changed the landscape of patent foramen ovale (PFO) closure for secondary stroke prevention. This review synthesizes the data and provides a framework for optimal management of stroke patients with PFO. The cumulative evidence indicates that PFO closure reduces the risk of recurrent stroke in carefully selected young cryptogenic stroke patients, with an annualized risk reduction of ∼0.6%. The benefit of PFO closure is particularly evident in patients with embolic appearing strokes, large right-to-left shunt, or an associated atrial septal aneurysm. There may be little or no benefit in patients with small deep infarcts, a small PFO, or an indication for long-term anticoagulation. Closure is accompanied by a small risk of major procedural complication and atrial fibrillation. The annual risk of stroke from PFO is low relative to other stroke mechanisms, but the life-time cumulative risk in young patients who have experienced a prior stroke may be substantial, in which case the absolute benefit of closure is likely impactful. PFO is highly prevalent in the general population, present in about one in four adults, and should not be considered to be the cause of the stroke until a thorough workup has excluded alternative mechanisms.

Perioperative Bridging of Anticoagulation - Does Protocol Adherence Improve Outcomes?

Background: Perioperative warfarin management is a clinical challenge as it requires careful assessment of both thrombosis and bleeding risk associated with the planned procedure. In our experience, many clinicians favor bridging over not bridging and often use full dose unfractionated or low molecular weight heparin even when a prophylactic dose would be a reasonable alternative. To improve and standardize the complex decision-making process for anticoagulation management for patients undergoing elective surgery we introduced an evidenced-based perioperative bridging anticoagulation protocol in 2017 based on the 9th edition of American College of Chest Physicians guidelines. The aim of the study was to investigate the impact of the perioperative bridging anticoagulation protocol on postoperative bleeding and thrombotic events in patients undergoing elective surgery at our institution. We hypothesized that adherence to the proposed protocol reduces the incidence of postoperative bleeding complications without an increase in thrombotic risk. Methods: We performed a retrospective chart review for all surgical inpatients who were on long-term anticoagulation with warfarin and who required interruption of warfarin around surgery at Dartmouth-Hitchcock Medical Center from June 2016, when the protocol was introduced, to June 2019. Data were extracted from the electronic medical record for each study subject and included demographics, clinical and radiologic data, indication for long-term anticoagulation (atrial fibrillation, venous thromboembolism, or mechanical heart valve), risk categories for thrombotic events, type of surgery, anticoagulation management before and after surgery including type and dose of short-acting anticoagulation used for bridging, and bleeding and thrombotic complications within 30 days of surgery. We evaluated adherence to the bridging protocol by individual providers and divided subjects into two groups for comparison: 1) subjects who received protocol-directed care and 2) subjects who received non-protocol care. We compared the risk of postoperative bleeding and thrombotic events in the two groups using the R3.5.1. Concordance of bridge protocol and crude associations between discrete variables were assessed by McNemar's and two-tailed Fisher's exact test, respectively. Multivariate logistic regression was used to estimate covariate-adjusted association groups and the outcomes of interest. P &amp;lt; 0.05 was used as the criterion for statistical significance. Results: 194 subjects met entry criteria and were included in the study; 114 subjects were managed according to the protocol (58.8%; 95% CI = 51.5%-65.8%, McNemar's P = 0.034). Clinical characteristics were similar in the protocol-adherent and nonadherent groups. Most patients (50%) were on long-term warfarin for stroke prevention with atrial fibrillation. The incidence of bleeding and thrombotic complications for the entire population was 7.8% and 4.7 %, respectively. Two-thirds of subjects who experienced either bleeding (66.7% vs 33.3%, 95% CI= 0.91-11.93, P = 0.055, two tailed Fischer's exact test) or thrombotic (66.7% vs 33.3%, 95% CI= 0.62-19.19, P = 0.16, two tailed Fischer's exact test) complications were in the protocol-nonadherent group. Controlling for age and sex using multivariate logistic regression, subjects whose anticoagulation was not managed postoperatively in adherence to the protocol were over three times as likely to experience a bleeding complication (adjusted odds ratio=3.36, 95% CI= 1.13-11.40, P = 0.036) and a thrombotic complication (adjusted odds ratio=3.54, 95% CI=0.88-17.77, P=0.088) when compared to patients whose postoperative anticoagulation management was protocol-driven. Discussion: Overall adherence to an evidence-based anticoagulation bridging protocol by providers was only 59%. When adhered to, protocol-based practice helped to reduce bleeding complications by 60% and was associated with a trend toward a lower risk for thrombosis. Our study results emphasize the value of an evidence-based perioperative anticoagulation bridging protocol and the importance of protocol adherence. To improve adherence, we have now embedded the protocol as an order-set in our electronic medical record system and have provided additional education to providers within our institution with a plan to assess improvement in adherence subsequently. Disclosures No relevant conflicts of interest to declare.

Outcomes in the Secondary Prevention of Cerebral Venous Thrombosis in Cancer Only Population

BACKGROUND AND PURPOSE:There are scant data on the outcomes of cerebral venous thrombosis (CVT) in the cancer only population. Current anticoagulation guidelines exist for the general population but the effect of these strategies in cancer subgroups are not known. We examined the clinical outcomes such as recanalization, thrombosis recurrence and major bleeding during cerebral venous thrombosis treatment in an exclusively cancer population.METHODS:A retrospective cohort study of cancer only patients with cerebral venous thrombosis identified through an institutional data warehouse at MD Anderson Cancer Center between January 2002 and June 2017. Patients with other indications for long term anticoagulation, chronic cerebrovascular thrombosis or less than 12 month follow up were excluded from the primary analysis. The primary end point was thrombus recanalization. Secondary end points were major bleeding and recurrence of cerebral or venous thrombosis. Demographic data, cancer diagnosis and cancer-therapy was also obtained at the time of initial CVT for further analysis. Chi-square test or Fisher exact test were used to assess the association between categorical variables.RESULTS:The population comprised predominantly male adults (55.6%) with median age 54.5 years, IQR [41.5 to 62.4]. The underlying malignancies were non-hematologic in 64.4% of cases. Anticoagulation was used in the treatment of 73.3% of cases, predominantly low molecular weight heparin (LMWH), and a median duration of 7.9 months, IQR [3.1 to 30.8]. Partial and complete recanalization were achieved in 33.3% and 17.8% of cases, respectively. The CVT recurrence rate at 12 months was 15.6% and 31% of patients suffered major bleeding. Most of the major bleeding events (71.1%) occurred outside the brain. Anticoagulation therapy with LWMH showed a trend to a higher rate of thrombus recanalization (p=0.196) without an increment in the overall bleeding events. We observed a lower rate of major bleeding events in patients treated with LWMH when compared with oral anticoagulation (5/14 versus 18/31, respectively; p=0.049).CONCLUSIONS:Our findings suggest that LMWH might represent an effective and safe strategy for the management of CVT in cancer patients. The findings are consistent with results from large randomized trials for outcomes of cancer associated venous thrombosis in other anatomical locations. The impact of thrombus recanalization in recurrent thrombosis and bleeding outcomes deserves further exploration. Limitations to our study are the retrospective and non-randomized design for the adjudication of treatment agents. DisclosuresNo relevant conflicts of interest to declare.

A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline.

The previous BSH guideline for the management of erythrocytosis was published in 2005 (McMullin et al, 2005) and amended in 2007 (McMullin et al, 2007). Here, we re‐evaluate the literature formulate guidance on the management of specific situations encountered in polycythaemia vera (PV) and the management of the other types of secondary erythrocytosis. Recommendations for the diagnostic pathway of investigation of an erythrocytosis, risk stratification and management of PV are in the accompanying guideline (McMullin et al, 2018). We review evidence and outline guidance on management of acute thrombotic events and secondary prevention of thrombosis in PV. The unusual thrombotic events, splanchnic vein and cerebral vein thromboses are discussed and haemorrhage. The specific situations of surgery and pregnancy and guidance on management of pruritus are included. The evidence for the management of other causes of erythrocytosis, including idiopathic erythrocytosis, congenital erythrocytosis, hypoxic pulmonary disease and post‐transplant erythrocytosis, is reviewed and recommendations made.