Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

High incidence of deep vein thrombosis during the treatment of pseudoaneurysms - a retrospective nonrandomized study.

Background: Pseudoaneurysms (PSAs) are concerning complications after arterial invasive interventions. Therapeutic options include manual ultrasound-assisted compression, pressure dressings, surgical intervention and thrombin injection. Compression of neighboring veins is obvious. However, the incidence of deep vein thrombosis (DVT) in patients with PSA has not previously been investigated. Patients and methods: In this retrospective, nonrandomized study 238 patients with PSA were analyzed from 2013 to 2018. In 149 patients, all of the parameters were complete for participating. PSAs were treated according to the local standard therapy with either ultrasound-guided compression followed by compression bandage or thrombin injection. Treatment success was evaluated 24 hours later, and the venous system was examined for the presence of DVT. Results: Peripheral DVT was found in 25.4% patients after ultrasound-assisted compression and subsequent pressure bandages, but only 6.4% of patients had DVT after thrombin injection (p = 0.013). Lower leg veins, particularly veins of the crural muscles, were primarily affected. Significantly more PSAs were successfully treated without the occurrence of DVT in the thrombin injection group compared to the compression group (93.6 vs. 69.0%; p = 0.001). Conclusions: Our study revealed that the use of thrombin injections resulted in a significantly lower rate of postinterventional DVT and a higher total number of successfully treated PSAs compared to compression therapy.

[Modern Finding-Specific and Patient-Adapted Management of Peripheral Pseudoaneurysms after Arterial Access]. / Das moderne befund- und patientenadaptierte Management von peripheren Pseudoaneurysmen nach arteriellem Zugang.

Aside from haematomas, pseudoaneurysms (PSA) are considered the most frequent complications after catheter-guided interventions. AIM AND METHOD: Narrative compact short overview to describe aetiopathogenesis and characteristics of pseudoaneurysms and the options for diagnostic measures, therapy and its complications. RESULTS: Aetiopathogenesis: via the closed access site, the puncture channel, there is continuous bleeding out of the vessel which forms a pseudoaneurysm-associated cavity within the perivascular tissue. This is not surrounded by a regular vascular wall as in true aneurysms but is only formed by the surrounding tissue structures. However, this border is not sufficient and the pseudoaneurysm may extend, with diffuse bleeding episodes into the tissue. Thus, surrounding structures such as nerves and veins can be compressed by the expanding pseudoaneurysm, which can lead to irreversible damage. Diagnostic measures: duplex ultra-sonography absolutely predominant. CT-A, MR-A and DSA for specific problems and clinical case characteristics (e.g., accompanying diseases etc.) - DSA is to be linked with the option of image-guided intervention during the same session. THERAPY: by manual compression and subsequent dressing with compression, ultrasound-guided compression, thrombin injection and surgical intervention, there are several therapeutic measures for appropriate selection according to the specific need. Ultrasound-guided compression should be immediately used since it is highly efficient and widely available. In addition to compression, thrombin can be injected into the pseudoaneurysm-preserving nerval structures and tissue from alterations. This provides much better occlusion rates but is more demanding. Surgical intervention is the most efficient approach to occlude a pseudoaneurysm but is demanding and can be associated with complications such as disturbances of wound healing in altered tissue and the longest hospital stay. Alternative approaches have not been established yet. CONCLUSION: The diagnostic and therapeutic management of pseudoaneurysms for different findings and patients can be considered a great challenge, and requires an experienced angiologist or vascular surgeon.

Cerebrovascular events, bleeding complications and device related thrombi in atrial fibrillation patients with chronic kidney disease and left atrial appendage closure with the WATCHMAN™ device.

BACKGROUND: Impaired renal function increases the bleeding risk, leading to a conservative prescription and frequent discontinuation of oral anticoagulation in atrial fibrillation patients with chronic kidney disease (CKD). Interventional left atrial appendage closure (LAAC) might be an alternative therapeutic strategy for these patients. METHODS: We aimed to prospectively assess cerebrovascular (CE) and bleeding events, as well as peri-procedural and long-term complications in a cohort of consecutive patients undergoing interventional LAAC using the WATCHMAN™ device, with focus on CKD patients. RESULTS: One hundred and eighty-nine consecutive patients undergoing interventional LAAC were included in this analysis; 171 (90.5%) patients had a reduced estimated glomerular filtration rate (eGFR; patients for each CKD stage: II = 66; IIIa = 32; IIIb = 43; IV = 18; V = 12). During a follow-up of 310 patient years three (1.0%) patients suffered a CE (two strokes, one transitory ischemic attack) and five (1.6%) other ones a bleeding complication. The observed stroke rate was more than two-thirds and the bleeding risk more than half lower than expected. Device related thrombi (DRT) were detected in twelve (6.5%) patients; women had significantly more DRT than men (12.5% vs. 2.6%; p = 0.009). Patients with an eGFR< 30 ml/min/1.73m2 showed a trend to a higher DRT rate as compared to the opposite group (13.3% vs. 5.1%; p = 0.10). Thrombus resolved with temporary oral anticoagulation therapy in ten patients without sequelae; thrombus consolidation was confirmed by serial TEE controls in the remaining two patients. CONCLUSIONS: Atrial fibrillation patients with CKD have low CE and bleeding rates after LAAC with the WATCHMAN™ device. DRT risk is higher in female and patients with severe CKD. More frequent post-interventional TEE controls might be justified for early DRT detection and safe management of patients at high DRT risk. TRIAL REGISTRATION: (German Clinical Trials Register ID: DRKS00 010768 ; Registration Date 07.07.2016).

Do not underestimate the femoral pseudoaneurysm.

In addition to haematoma and arteriovenous fistula, the iatrogenic pseudoaneurysm is a common complication of vascular access that is caused by a perforation in the arterial wall. Iatrogenic pseudoaneurysms can progress in size and lead to rupture and active bleeding. Over the previous few decades, therapeutic methods have evolved from surgical repair to less invasive options, such as ultrasound-guided compression therapy (UGCT) and ultrasound-guided thrombin injection (UGTI). This paper presents an overview of the diagnostic and treatment modalities used in femoral pseudoaneurysms as well as a comprehensive summary of previous studies that analysed the success and complication rates of UGCT and UGTI.

Serial Assessment of Natriuretic Peptides in Patients Undergoing Interventional Closure of the Left Atrial Appendage.

BACKGROUND: Closure of the left atrial appendage (LAA) to prevent cardioembolic events is an alternative therapy to oral anticoagulation in patients with non-valvular atrial fibrillation. The LAA is an important source of natriuretic peptides and its exclusion from the circulation may alter the blood level of these hormones, thereby influencing their diagnostic value and clinical effects. METHODS: We aimed to prospectively assess potential changes in mid-regional pro A-type natriuretic peptide (MR-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels 6 weeks and 6 months after interventional LAA closure using the WATCHMAN device. RESULTS: In 29 consecutive patients with successful LAA closure baseline MR-proANP level was 274±208pmol/l and decreased by -24.5±68 (p=0.07) and -15.0±44pmol/l (p=0.10) after 6 weeks and 6 months, respectively. The drop in the MR-proANP level after 6 weeks and 6 months was significant in patients with elevated (≥214pmol/l) baseline MR-proANP level (n=15: -54.3±78.0, p<0.01 and -31.8±45.4pmol/l, p=0.03, respectively) and those with reduced left ventricular ejection fraction (LVEF<45%, n=7: -87.4±97.3, p=0.02 and -60.3±42.6pmol/l, p=0.01, respectively). Baseline NT-proBNP level (median 1054pg/ml; IQR 621-1977pg/ml), sodium, potassium, mean systolic or diastolic blood pressure did not change significantly in the mentioned patient groups. CONCLUSIONS: After LAA closure, MR-proANP level decreased significantly in patients with elevated baseline MR-proANP level or reduced LVEF, whereas NT-proBNP level remained unchanged, thereby altering the correlation coefficient between the two biomarkers. Our findings should be considered when using these biomarkers for diagnostic or prognostic evaluation in patients with interventional LAA closure.

Analysis of cardiovascular mortality, bleeding, vascular and cerebrovascular events in patients with atrial fibrillation vs. sinus rhythm undergoing transfemoral Transcatheter Aortic Valve Implantation (TAVR).

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been demonstrated to be an established therapy for high-risk, inoperable patients with severe symptomatic aortic valve stenosis. For patients with moderate surgical risk, TAVR is equivalent to conventional aortic valve surgery. However, atrial fibrillation (AF) is also present in many of these patients, thus requiring post-implantation oral anticoagulation therapy in addition to the inhibition of thrombocyte aggregation, which poses the risk of bleeding complications. The aim of our work was to investigate the influence of AF on mortality and the occurrence of bleeding, vascular and cerebrovascular complications related to TAVR according to the VARC-2 criteria. METHODS: Two hundred eighty-three patients who underwent TAVR between March 2010 and April 2016 were retrospectively examined. In total, 257 patients who underwent transfemoral access were included in this study. The mean patient age was 81 ± 6 years, 54.1% of the patients were women, and 42.4% had pre-interventional AF. RESULTS: Compared to patients with sinus rhythm (SR, n = 148), patients with AF (n = 109) had an almost three-fold higher incidence of major vascular complications (AF 14.7% vs. SR 5.4%, p = 0.016) and life-threatening bleeding (AF 11.9% vs. SR 4.1%, p = 0.028) during the first 30 post-procedural days. However, the rate of cerebrovascular complications (AF 3.7% vs. SR 2.7%, p = 0.726) did not significantly differ between the two groups. Overall mortality was significantly higher in patients with AF during the first month (AF 8.3% vs. SR 2.0%, p = 0.032) and the first year (AF 28.4% vs. SR 15.3%; p = 0.020) following TAVR. CONCLUSION: Patients with AF had significantly more severe bleeding complications after TAVR, which were significantly related to mortality. Future prospective randomized studies must clarify the optimal anticoagulation therapy for patients with AF after TAVR. TRIAL REGISTRATION: DRKS00011798 on DRKS (Date 17.03.2017).

Left atrial enlargement and clinical considerations in patients with or without a residual interatrial shunt after closure of the left atrial appendage with the WATCHMAN™-device.

BACKGROUND: Interventional closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, high thromboembolic and bleeding risk or bleeding history is an alternative therapeutic strategy to oral anticoagulation. It is not known if the exclusion of the LAA from the blood circulation affects the left atrial volume (LAV) and consequently its prognostic value or the circulatory performance of the heart in humans. METHODS: We aimed to prospectively assess potential changes in baseline LAV, left ventricular ejection fraction (LVEF), NT-proBNP-level and the covered distance in the 6-min walk-test 6 weeks and 6 months after LAA closure with the WATCHMAN™ device. We used serial 3-dimensional transthoracic and transesophageal echocardiography to assess LAV, residual interatrial shunt and device performance in 58 consecutive patients with successful LAA closure. RESULTS: Accurate 3D-echocardiographic data for LAV measurements were evaluable for 51 (91%) patients. Maximum LAV (LAVmax) at baseline was 102.8 ± 30.8 ml and increased significantly to 107.7 ± 32.8 ml after 6 weeks (p < 0.01) and 113.5 ± 34.2 ml after 6 months (p < 0.01). Minimal LAV (LAVmin) increased from 76.9 ± 29.5 ml at baseline to 81.8 ± 30.2 ml after 45 days (p < 0.01) and 82.1 ± 33.3 ml after 6 months (p < 0.01). Similarly, their indexes to BSA (LAVImax and LAVImin) increased significantly, as well. Patients without a residual left-to-right interatrial shunt showed a significantly higher increase in LAVmax or LAVmin. Baseline LVEF, NT-proBNP-level or the distance covered at the 6-min walk test did not significantly change 6 weeks or 6 months after LAA closure. CONCLUSIONS: LAVmax and LAVmin increase significantly after interventional LAA closure. LA enlargement does not correlate with clinical progression of heart failure. Persistent left-to-right interatrial shunt counteracts the LA enlargement. A reduced LA compliance after exclusion of the LAA from the blood circulation with consecutive increase in LA pressure may be a potential cause of LA enlargement and warrants further investigation. TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00010768 ; Registration Date 07.07.2016.

Effects of the Peroxisome Proliferator-Activated Receptor-γ Agonist Pioglitazone on Peripheral Vessel Function and Clinical Parameters in Nondiabetic Patients: A Double-Center, Randomized Controlled Pilot Trial.

OBJECTIVE: Despite the advanced therapy with statins, antithrombotics, and antihypertensive agents, the medical treatment of atherosclerotic disease is less than optimal. Therefore, additional therapeutic antiatherosclerotic options are desirable. This pilot study was performed to assess the potential antiatherogenic effect of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in nondiabetic patients. METHODS: A total of 54 nondiabetic patients were observed in a prospective, double-blind, placebo-controlled study. Patients were randomized to pioglitazone or placebo. The following efficacy parameters were determined by serial analyses: artery pulse wave analysis and carotid-femoral pulse wave velocity (PWV), static and dynamic retinal vessel function, and the common carotid intima-media thickness (IMT). The main secondary endpoint was the change in different biochemical markers. RESULTS: After 9 months, no relevant differences could be determined in the two treatment groups in PWV (pioglitazone 14.3 ± 4.4 m/s vs. placebo 14.2 ± 4.2 m/s), retinal arterial diameter (pioglitazone 112.1 ± 23.3 µm vs. placebo 117.9 ± 21.5 µm) or IMT (pioglitazone 0.85 ± 0.30 mm vs. placebo 0.79 ± 0.15 mm). Additionally, there were no differences in the change in biochemical markers like cholesteryl ester transfer protein, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein or white blood cell count. CONCLUSIONS: Treatment with a peroxisome proliferator-activated receptor-γ agonist in nondiabetic patients did not improve the function of large and small peripheral vessels (PPP Trial, clinicaltrialsregister.eu: 2006-000186-11).

Feasibility of a new method using two-dimensional transesophageal echocardiography for aortic annular sizing in patients undergoing transcatheter aortic valve implantation; a case-control study.

BACKGROUND: Accurate preoperative assessment of the aortic annulus dimension is crucial for successful transcatheter aortic valve implantation (TAVI). In this study we validated a new method using two-dimensional transesophageal echocardiography (2D-TEE) for measurement of the aortic annulus prior to TAVI. METHODS: We analysed 124 patients who underwent successful TAVI using a self-expandable prosthesis, divided equally into two groups; in the study group we used the cross sectional short axis 2D-TEE for measurement of the aortic annulus and in the control group we used the long axis 2D-TEE. RESULTS: Both groups were comparable regarding the clinical parameters. On the other hand, patients in the study group had less left ventricular ejection fraction (38.9 % versus 45.6 %, p = 0.01). The aortic valve annulus was, although not statistically significant, smaller in the study group (21.58 versus 23.28 mm, p = 0.25). Post procedural quantification of the aortic regurgitation revealed that only one patient in both groups had severe aortic regurgitation (AR), in this patient the valve was implanted deep. The incidence of significant AR was higher in the control group (29.0 % versus 12.9 %, p = 0.027). CONCLUSIONS: Sizing of the aortic valve annulus using cross-sectional 2D-TEE offers a safe and plausible method for patients undergoing TAVI using the self-expandable prosthesis and is significantly superior to using long axis 2D-TEE.

Effects of the PPARγ agonist pioglitazone on coronary atherosclerotic plaque composition and plaque progression in non-diabetic patients: a double-center, randomized controlled VH-IVUS pilot-trial.

Despite the advanced therapy with statins, antithrombotics and antihypertensive agents, the medical treatment of coronary artery disease is less than optimal. Therefore, additional therapeutic anti-atherosclerotic options are desirable. This VH-IVUS study (intravascular ultrasonography with virtual histology) was performed to assess the potential anti-atherogenic effect of the PPARγ agonist pioglitazone in non-diabetic patients. A total of 86 non-culprit atherosclerotic lesions in 54 patients with acute coronary syndrome were observed in a 9-month prospective, double-blind, and placebo-controlled IVUS study. Patients were randomized to receive either 30 mg pioglitazone (Pio) or placebo (Plac). As primary efficacy parameter, the change of relative plaque content of necrotic core was determined by serial VH-IVUS analyses. Main secondary endpoint was the change of total plaque volume. In contrast to placebo, in the pioglitazone-treated group, the relative plaque content of necrotic core decreased significantly (Pio -1.3 ± 6.9% vs. Plac +2.6 ± 6.5%, p < 0.01). In comparison to the placebo group, the plaques in pioglitazone-treated patients showed significantly greater reduction of the total plaque volume (Pio -16.1 ± 26.4 mm3 vs. Plac -1.8 ± 30.9 mm3, p = 0.02). Treatment with a PPARγ agonist in non-diabetic patients results in a coronary artery plaque stabilization on top of usual medical care.

Acute Abdominal Pain as a Result of an Isolated Left Ovarian Vein Thrombosis.

Ovarian vein thrombosis (OVT) is a rare thromboembolic condition. It involves the right ovarian vein in 70-80% of cases. The risk factors for the development of OVT are pregnancy or puerperium, hormone therapy with estrogen, recent surgery or hospitalization, malignancy, pelvic inflammatory diseases, thrombophilia and idiopathic OVT. We present a rare case of left OVT in a young, non-pregnant woman in her 30 s. A high degree of suspicion is necessitated in patients with the triad of young-middle-aged female, pain abdomen in lower quadrant and hematuria to diagnose OVT. Contrast enhanced computer tomography (CT-venography) is the diagnostic modality of choice. The patient was initially treated with low molecular weight heparin and then switched to direct oral anticoagulants. At 6-monthsfollow-up the patient was free from any symptoms.

Fatal heat stroke based on foudroyant irreversible multiple organ dysfunction in German summer.

Objectives: Heat stroke is a serious condition that might lead from moderate organ impairment to multiple organ dysfunction syndrome. Appropriate diagnosis-finding, fast initiation of cooling and intensive care are key measures of the initial treatment. Scientific case report based on i) clinical experiences obtained in the clinical management of a particularly rare case and ii) selected references from the medical scientific literature. Case presentation: We present a case of a young and healthy construction worker who suffered from an exertional heat stroke with a body core temperature exceeding 42 °C by previous several hour work at 35 °C ambient temperature. Heat stroke was associated with foudroyant, not reversible multiple organ dysfunction syndrome, in particular, early disturbed coagulation, microcirculatory, liver and respiratory failure, and subsequent fatal outcome despite immediate diagnosis-finding, rapid external cooling and expanded intensive care management. Conclusions: Basic knowledge on an adequate diagnosis(-finding in time) and treatment of heat stroke is important for (almost each) physician in the summertime as well as is essential for the initiation of an appropriate management. Associated high morbidity and mortality rates indicate the need for implementation of standard operation protocols.

The Role of Anticoagulants and Platelet Aggregation Inhibitors in the Treatment of Pseudoaneurysms and Risk of Venous Thrombosis.

Pseudoaneurysms (PSA) are one of the most common complications after arterial punctures. This retrospective study examined whether platelet aggregation inhibitors (APT) or anticoagulants (AC) lower the success rates of PSA treatment. A total of 468 patients with PSA were retrospectively analyzed between 2010 and 2018, and 238 were included in the study. Despite co-medication with APT or AC, thrombin injection (TI) was superior to compression bandage (CB) therapy in treating PSA (TIwAC 79 vs CBwAC 51%; P = .004 and TIwAPT 93 vs CBwAPT 54%; P = .001). There was no decrease in PSA-associated thrombosis in patients requiring anticoagulation after TI. The success rates of the TI and CB groups were compared in patients with and without AC therapy, and the latter was significantly lower. A reduced success rate was not observed in CB therapy patients requiring APT. In contrast, better results were seen in the TI group. Regarding PSA treatment, TI therapy is significantly superior to CB, including in patients requiring concomitant AC or APT therapy. PSA-associated thrombosis also occurs in patients requiring anticoagulation, and sonography should be performed. Concomitant medication use with APT does not significantly influence PSA therapy success or prevention of PSA-associated thrombosis.

[How to anticoagulate elderly and fragile patients?] / Wie antikoaguliert man ältere und fragile Patienten?

Risks of thrombosis, bleeding and renal impairment are increasing with age. The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age > 75 years and/or creatinine clearance levels < 50 ml/min and/or body weight below 50 kg) with indication for anticoagulation is one of the most challenging topic in cardiovascular medicine. New registry data from subgroup analyses of landmark studies and registries point towards to superiority of DOACs. This article summarizes new insights and describes pathways for anticoagulation in fragile patients.

Oral Anticoagulation in the Elderly and Frail.

The proportion of elderly patients will increase substantially over the next decades, and both atrial fibrillation (AF) and venous thromboembolism (VTE) are more common in the elderly. Age is a risk factor not only for stroke and thromboembolism but also for bleeding, particularly in frail patients, in whom numerous pathophysiological changes occur that alter drug kinetics and toxicity of standard doses of oral anticoagulants (OACs). AF trials showed that the relative benefits of direct OACs (DOACs) also applied to elderly patients, and due to their higher risk this translates into a higher absolute risk reduction compared with vitamin K antagonists, suggesting that DOACs are the better choice. All DOACs-at varying extent-are eliminated via the kidney and it is crucial to evaluate renal function at initiation and during follow-up, especially for dabigatran. The fear of falls is a common reason against OAC. However, there is still a benefit with OAC, particularly with DOACs given the lower risk of intracranial hemorrhage. Polypharmacy represents a common challenge, nevertheless DOACs and warfarin were classified as beneficial. Nonetheless, attempts should be undertaken to reduce comedication, and drug-drug interactions should be assessed. Coadministration of platelet inhibitors increases bleeding risk and should be avoided. In conclusion, elderly and frail patients requiring anticoagulation for AF or VTE are at higher risk of adverse outcomes, but also have a higher absolute benefit from OAC. Important practical aspects to improve efficacy and safety in this challenging population are summarized in this overview.

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. METHODS: MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel-Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43-0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83-2.08; I 2, 23%). CONCLUSION: In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.