Recurrent Venous Thromboembolism Complications Research Articles

Role of anticoagulants in therapy and prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis of randomized trials with apixaban

Background Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.

Efficiency and safety of direct oral anticoagulants in onco-associated venous thromboembolic complications: meta-analysis

The work aimed to analyze the efficiency and safety of direct oral anticoagulants in treating onco-associated venous thromboembolic complications. Materials and methods . A meta-analysis of randomized controlled trials was performed in accordance with the guidelines “Preferred reporting parameters for systematic reviews and meta-analyses.” Results . Data from four randomized controlled trials were used to perform the meta-analysis. Direct oral anticoagulants reduce the relative risk of recurrent venous thromboembolic complications compared with dalteparin by 38% (relative ratio [RR]=0.62; 95% confidence interval [CI] [0.43–0.91]; p =0.01) and reduce statistically significantly the risk of deep vein thrombosis by 40% (RR=0.60; 95% CI [0.40–0.90]; p =0.01). In the effectiveness of prevention of repeated pulmonary embolism, the compared technologies are comparable (RR=0.89; 95% CI [0.52–1.51]; p =0.66). A safety meta-analysis suggests that direct oral anticoagulants are comparable in safety compared with dalteparin, in terms of major bleeding incidences (RR=1.33; 95% CI [0.84–2.11]; p =0.23) and in relation to gastrointestinal bleeding development (RR=1.91; 95% CI [0.96–3.82]; p =0.07). Direct oral anticoagulants increased the incidence of clinically significant minor bleeding (RR=1.58; 95% CI [1.11–2.24]; p =0.01).

Pathogenesis and prevention of venous and arterial thromboembolic events in patients after deep vein thrombosis of lower extremities

To define the role of thrombophilic and other procoagulant conditions in pathogenesis of deep vein thrombosis and the effectiveness of pathogenetic secondary prevention of venous and arterial thromboembolic events. The study included 107 patients for the period 2007-2016 who were divided into 3 groups. The main group (n=40) - lifelong individual antithrombotic therapy with warfarin predominantly; the second (control) group (n=39) - warfarin administration for 3-6 months; the third (additional) group (n=28) - specific life-long therapy depending on procoagulant status which was assessed according to original scale. The main anticoagulants were rivoroxaban or dabigatran etexilate. Recurrent venous thromboembolic complications (RVTE) were observed in one (2.5%) patient of the first group and in 8 (20.5%) cases of the second group. In the third group RVTE were absent (significant differences, p<0.03 and 0.001, respectively). Arterial thromboembolic diseases were noted in 1 (2.5%) patient of the first group, in 4 (10.25%) cases of the second group and in none of the third group (significantly only for group II vs. group III, p<0.01). Individual antithrombotic therapy reduces the incidence of recurrent venous and arterial thromboembolic events in patients with idiopathic deep vein thrombosis.

CLINICAL DISCUSSION OF A PATIENT WITH RECURRENT VENOUS THROMBOEMBOLIC COMPLICATIONS

The article presents a clinical discussion of the patient with recurrent venous thromboembolic complications. It also provides recommendations on modern principles of diagnostics, choice of medical tactics in patients with this pathology. Much attention is paid to the issues of anticoagulant treatment, which inadequacy or failure results in the development of severe, difficultly treatable complications.

Clinical Outcomes and Adherence to Guideline Recommendations During the Initial Treatment of Acute Venous Thromboembolism

Adherence to American College of Chest Physicians (CHEST) guidelines for treatment of acute venous thromboembolism (VTE) has not been formally assessed in the United States, specifically in the subset of patients with renal impairment. Evaluate adherence to CHEST VTE treatment guidelines. This retrospective cohort study evaluated patients with acute VTE between January 1, 2010, and December 31, 2011, for the primary outcome of adherence to CHEST VTE treatment guidelines defined as (1) patients receiving an appropriate parenteral anticoagulant and dose based on renal function and weight, (2) at least 5 days of parenteral anticoagulation during warfarin initiation, and (3) an international normalized ratio (INR) value ≥2 documented before discontinuing parenteral agents. Secondary outcomes included recurrent thromboembolism and major bleeding across renal function categories. Of the 1683 patients included in the final analysis, 1483 (88%) had complete data for all 3 elements of the primary outcome (dose, overlap duration, and INR ≥2.0). VTE guideline adherence was identified in 95% (1408/1483) of these patients. There were 20 major bleeds overall, which occurred in 1.1%, 1.1%, and 1.3% in patients with CrCl <30 mL/min, 30 to 59 mL/min, and ≥60 mL/min, respectively (P = 0.929). Also, 7 recurrent VTE events occurred-3 in patients with CrCl values of 30 to 59 mL/min (0.5%) and 4 in patients with CrCl ≥60 mL/min (0.4%; P = 0.797 across groups). Adherence to CHEST guidelines was high and resulted in low rates of bleeding and recurrent VTE complications across renal function categories. Further studies of patients with CrCl <30 mL/min are needed.

Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis

A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included patients, 181 had known cancer at entry. The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7% (95% CI, 15.6%-25.8%) versus 6.8% (95% CI, 3.9%- 9.7%) in patients without cancer, for a hazard ratio of 3.2 (95% CI, 1.9-5.4) The 12-month cumulative incidence of major bleeding was 12.4% (95% CI, 6.5%-18.2%) in patients with cancer and 4.9% (95% CI, 2.5%-7.4%) in patients without cancer, for a hazard ratio of 2.2 (95% CI, 1.2-4.1). Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation. Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy. These risks correlate with the extent of cancer. Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed.

Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis

Carriers of a mutation in the prothrombin (clotting factor II) or factor V gene have a 2- to 4-fold greater risk for venous thromboembolism than subjects without the mutations. Whether both mutations also predispose to recurrent venous thromboembolism is unclear. Outpatients who had a first episode of proven symptomatic deep-vein thrombosis and a long-term follow-up were studied. The outcome measure was the cumulative incidence of confirmed venous thromboembolic complications. Two hundred fifty-one patients were enrolled in the study. Mean duration of follow-up was 8.3 years. The prothrombin gene mutation was demonstrated in 27 patients (prevalence, 10.8%; 95% CI, 6.9 to 14.6), and the factor V gene mutation was demonstrated in 41 patients (prevalence, 16.3%; 95% CI, 11.8 to 20.9). The cumulative incidence of venous thromboembolic complications after 10 years was 61.3% (95% CI, 35.7 to 87.9), and the hazard ratio was 2.4 (95% CI, 1.3 to 4.7; P = .004) in patients with the prothrombin gene mutation); the cumulative incidence of venous thromboembolic complications after 10 years was 55.2% (95% CI, 36.4 to 74.0), and the hazard ratio was 2.4 (95% CI, 1.4 to 4.1;P = .001) in patients with the factor V gene mutation. In comparison, the cumulative incidence of venous thromboembolic complications after 10 years was 23.1% (95% CI, 16.2 to 30.1) in patients without the mutations. Prothrombin and factor V gene mutations occur frequently in patients with venous thrombosis and are associated with an increased risk for recurrent venous thromboembolic complications