Oral Rivaroxaban Versus Warfarin After inferior Vena cava Filter Implantation: A Retrospective Cohort Study.

OBJECTIVES: To assess the efficacy and safety of rivaroxaban compared to warfarin after inferior vena cava (IVC) filter implantation. METHOD: This retrospective analysis includes data from 100 patients with deep vein thrombosis (DVT) who underwent IVC filter implantation due to a free-floating thrombus (n = 64), thrombus propagation (n = 8), or acute bleeding (n = 8) on therapeutic anticoagulation, catheter-directed thrombolysis (n = 8), or had previously implanted filter with DVT recurrence. Patients were treated with warfarin (n = 41) or rivaroxaban (n = 59) for 3-12 months. Symptomatic venous thromboembolism (VTE) recurrence and bleeding events were assessed at 12 months follow-up. RESULTS: Three (7.3%) cases of VTE recurrence without IVC filter occlusion occurred on warfarin and none on rivaroxaban. The only (2.4%) major bleeding occurred on warfarin. Three (5.1%) clinically relevant non-major bleedings were detected on rivaroxaban. No significant differences existed between groups when full and propensity scores matched datasets were compared. CONCLUSIONS: Rivaroxaban seems not less effective and safe than warfarin after IVC filter implantation.

A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis.

OBJECTIVE: The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism (VTE) in patients with superficial venous thrombosis (SVT). METHODS: A systematic review and meta-analysis were performed using searches of Medline and Cochrane Library databases in September 2023. Papers that provided VTE incidence within mid-term follow-up of ≥45 days in patients who received any ACT were included. Patients were categorized into subgroups according to the course of treatment: (1) no ACT (0 days); (2) ACT of ≤14 days; (3) ACT of 15 to 30 days; (4) ACT of 31 to 45 days; and (5) ACT of >45 days. Reported events were transformed to events per 100 patient-years, and a random-effects model was used to calculate pooled rates for proportions. The primary outcome (VTE) was a combination of SVT progression or recurrence with the occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE). Secondary outcomes included major and clinically relevant non-major or minor bleeding. RESULTS: Twenty-four studies (10 randomized controlled trials and 14 cohort studies) combining outcomes in 12,341 patients were included in the quantitative synthesis. Minimum VTE and SVT recurrence or progression rates were observed with the ACT duration of 31 to 45 days of 16.2 (95% confidence interval [CI], 10.4-23.3) and 8.2 (95% CI, 3.1-15.8) events per 100 patient-years, respectively. Minimum DVT and PE rates observed with the treatment duration of 15 to 30 days were 5.5 (95% CI, 2.8-9.1) and 0.9 (95% CI, 0.5-1.3) events per 100 patient-years, respectively. Short-term treatment of ≤14 days was associated with the highest rates of VTE of 59.7 (95% CI, 37.7-86.4), DVT of 13.7 (95% CI, 9.6-18.4), and PE of 3.1 (95% CI, 1.4-5.6) events per 100 patient-years. Major bleeding rates were unrelated to the duration of ACT and did not exceed 0.5 events per 100 patient-years. The highest rate of clinically relevant non-major or minor bleeding was observed with ACT duration of 31 to 45 days of 14.2 (95% CI, 5.5-26.8) events per 100 patient-years. The most common risk factors for VTE included male sex, cancer, personal history of DVT, PE, or SVT, and thrombosis of non-varicose veins. CONCLUSIONS: Prolonged systemic anticoagulation is associated with the tendency to decrease VTE rates in patients with lower limb SVT.

The trends in venous thromboembolism occurrence and prevention after minimally invasive varicose vein surgery.

OBJECTIVES: To assess the trends of VTE occurrence and prevention in varicose vein surgery. METHOD: The registry-based CAPSIVS trial (NCT03041805) analysis includes results in 1878 lower limbs. The primary outcome is a 28-day symptomatic or asymptomatic DVT revealed with duplex ultrasound. RESULTS: Any DVT, including EHIT, was observed in 3.4%, while symptomatic in 0.5%. Prophylactic anticoagulation was administrated in 20.4% with LMWH (13.2%) or DOAC (7.1%) for patients with higher VTE risk but did not reduce the events rate. With propensity score matching DOACs were superior to LMWHs (1.5% vs 9.8%). Duration of anticoagulation was essential: the lowest incidence (4.2%) was associated with prophylaxis for up to 7 days, while a single LMWH injection resulted in a DVT rate of 8.8%. With individual VTE history, any anticoagulation duration appeared insufficient. CONCLUSIONS: Prophylactic anticoagulation after varicose vein surgery should be based on the individual VTE risk and provided for ≥7-30 days.

The correlation between Caprini score and the risk of venous thromboembolism after varicose vein surgery.

BACKGROUND: The study aims to identify the incidence of symptomatic and asymptomatic venous thromboembolism (VTE) after minimally invasive varicose vein surgery and to assess the predictability of the Caprini risk score (CRS). METHODS: CAPrini Score In Venous Surgery (NCT03041805) is a registry-based prospective study that enrolls patients undergoing minimally invasive open (high ligation, stripping, miniphlebectomy) and endovascular (thermal and non-thermal ablation) surgery on varicose veins. The main inclusion criteria are CRS assessment before intervention and a duplex ultrasound scan performance within 2-4 weeks after surgery. The primary outcome is a combination of asymptomatic or symptomatic DVT, including EHIT of class 2-4 and PE. RESULTS: Totally 1878 records with defined outcomes were analyzed. The mean age of patients was 46.9±13.3 years; 66% were female. Endovenous laser ablation was performed in 88%. Varicose tributaries were treated in 40%, perforating veins in 3.9% of cases. CRS ranged from 1 to 12 (mean of 4.0±1.5). Prophylactic anticoagulation was prescribed in 20%. The primary outcome was reported in 63 cases (3.4%; 95% CI, 2.7-4.3%), comprising asymptomatic (N.=29, 1.5%) or symptomatic (N.=10, 0.5%) DVT or EHIT (n=28, 1.6%). No PE was reported. A significant correlation was found between CRS and VTE incidence (P=0.001). Under logistic regression CRS (OR, 1.3; 95% CI, 1.1-1.6) along with treatment of tributaries (OR, 6.3; 95% CI, 3.0-13.0) and perforating veins (OR, 10.7; 95% CI, 3.8-30.2) were associated with VTE in the absence of prophylactic anticoagulation. CONCLUSIONS: The incidence of VTE after ablation of superficial veins is 3.4%, predominantly due to asymptomatic EHIT and DVT, and significantly correlates with CRS.

The original and modified Caprini score equally predicts venous thromboembolism in COVID-19 patients.

OBJECTIVE: The study aimed to validate the original Caprini score and its modifications considering coronavirus disease (COVID-19) as a severe prothrombotic condition in patients admitted to the hospital. METHODS: The relevant data were extracted from the electronic medical records with an implemented Caprini score and were retrospectively evaluated. The score was calculated twice: by the physician on admission and by the investigator at discharge (death). The final assessment considered additional risk factors that occurred during inpatient treatment. Besides the original Caprini score (a version of 2005), the modified version added the elevation of D-dimer and specific scores for COVID-19 as follows: two points for asymptomatic, three points for symptomatic, and five points for symptomatic infection with positive D-dimer. Cases were evaluated retrospectively. The primary end point was symptomatic venous thromboembolism (VTE) detected during inpatient treatment and confirmed by appropriate imaging testing or autopsy. The secondary end points included those observed during hospitalization (admission to the intensive care unit, a requirement for invasive mechanical ventilation, death, bleeding), and those assessed at 6-month follow-up (symptomatic VTE, bleeding, death). The association of eight different versions of the Caprini score with VTE events was evaluated. RESULTS: A total of 168 patients (83 males and 85 females at the age of 58.3 ± 12.7 years) were admitted to the hospital between April 30 and May 29, 2020, and were discharged or died to the time of data analysis. The original Caprini score varied between 2 and 12 (5.4 ± 1.8) at the admission and between 2 and 15 (5.9 ± 2.5) at discharge or death. The maximal score was observed with modification including specific COVID-19 points of 5 to 20 (10.0 ± 3.0). Patients received prophylactic (enoxaparin 40 mg once daily: 2.4%), intermediate (enoxaparin 80 mg once daily: 76.8%), or therapeutic (enoxaparin 1 mg/kg twice daily: 20.8%) anticoagulation. Despite this, symptomatic VTE was detected in 11 (6.5%) inpatients. Of the 168 individuals, 28 (16.7%) admitted to the intensive care unit, 8 (4.8%) required invasive mechanical ventilation, and 8 (4.8%) died. Clinically relevant nonmajor bleeding was detected in two (1.2%) cases. The Caprini score of all eight versions demonstrated a significant association with inpatient VTE frequency. The highest predictability was observed for the original scale when assessed at discharge (death). Only symptomatic VTE was reported after discharge with a cumulative incidence of 7.1%. This did not affect the predictability of the Caprini score. Extended antithrombotic treatment was prescribed to 49 (29%) patients with a cumulative incidence of bleeding of 1.8% at 6 months. CONCLUSIONS: The study identified a significant correlation between the Caprini score and the risk of VTE in patients with COVID-19. All models including specific COVID-19 scores showed equally high predictability, and use of the original Caprini score is appropriate for patients with COVID-19.

Intermittent Pneumatic Compression in Addition to Standard Prophylaxis of Postoperative Venous Thromboembolism in Extremely High-risk Patients (IPC SUPER): A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of adjunctive IPC to standard prophylaxis of postoperative VTE in patients at extremely high-risk. SUMMARY OF BACKGROUND DATA: The standard prophylaxis for postoperative VTE is insufficient in extremely high-risk patients. It is unclear whether an adjunctive use of IPC would result in a lower incidence of postoperative venous thrombosis. METHODS: We randomly assigned patients who underwent major surgery and had a Caprini score of ≥11 to receive either IPC in addition to standard prophylaxis with anti-embolic stockings (pressure of 18-21 mm Hg at the ankle) and low-molecular-weight heparin (IPC group) or standard prophylaxis alone (control group). The primary outcome was an asymptomatic venous thrombosis of the lower limbs, as detected by duplex ultrasound scan performed before inclusion and every 3-5 days after surgery. RESULTS: A total of 407 patients underwent randomization, of which 204 were assigned to the IPC group and 203 to the control group. The primary outcome occurred in 1 (0.5%) patient in the IPC group and 34 (16.7%) patients in the control group [relative risk, 0.03, 95% confidential interval (CI): 0.01-0.21]. Pulmonary embolism occurred in none of the 204 patients in the IPC group and in 5 (2.5%) patients in the control group (relative risk, 0.09; 95% CI, 0.01-1.63), and postoperative death occurred in 6 (2.9%) patients in the IPC group and 10 (4.9%) in the control group (relative risk, 0.50; 95% CI, 0.50-1.60). CONCLUSIONS: Among patients with a Caprini score of ≥11 who received standard prophylaxis for VTE, adjunctive IPC resulted in a significantly lower incidence of asymptomatic venous thrombosis.

Diosmin 600 in adjunction to rivaroxaban reduces the risk of post-thrombotic syndrome after femoropopliteal deep vein thrombosis: results of the RIDILOTT DVT study.

BACKGROUND: To assess the efficacy and safety of long-term diosmin 600 therapy added to rivaroxaban and elastic compression stockings (ECS) in patients with femoropopliteal deep vein thrombosis (DVT). METHODS: This single-center, open-label randomized clinical trial RIDILOTT DVT enrolled patients with their first femoropopliteal DVT confirmed by duplex ultrasound scan (DUS). Participants were randomly allocated to the control group (standard treatment with rivaroxaban for six months and ECS for 12 months) or the experimental group (standard treatment with the additional use of diosmin 600 mg once daily for 12 months). Patients were followed for 12 months. The primary outcome was post-thrombotic syndrome (PTS), according to the Villalta Score (≥5). The secondary outcomes were deep vein recanalization, chronic venous disease (CVD) progression, the severity of PTS (Villalta), and CVD (VCSS), quality of life (CIVIQ-20), venous thromboembolism recurrence, and adverse event (AE). RESULTS: Ninety patients were randomized (45 per group). There were 56 men and 34 women with a mean age of 57.8±13.4 years, and 69% had clinically unprovoked DVT. PTS frequency at 12 months was significantly lower (8.9% vs. 48.9%) in the experimental group compared with control one (relative risk, 0.14; 95% confidential interval, 0.04-0.43, P<0.001). Adding diosmin 600 was associated with quicker and complete vein recanalization, lower CVD progression rate, and lower Villalta, VCSS, and CIVIQ-20 scores. There was no difference in recurrent DVT or AE. CONCLUSIONS: Adjunctive use of diosmin 600 to rivaroxaban and ECS in patients with femoropopliteal DVT can improve the clinical and ultrasound outcomes after 12 months of treatment.

The frequency and clinical significance of nontarget superficial and deep vein occlusion after physician compounded foam sclerotherapy of varicose tributaries.

OBJECTIVE: To evaluate the incidence and clinical relevance of silent nontarget occlusion (NTO) of superficial and deep veins occurring after ultrasound-guided foam sclerotherapy (UGFS) that can be detected by serial duplex ultrasound scan (DUS). METHODS: This retrospective analysis evaluated the medical records of patients treated with UGFS at a private clinic in Moscow, Russia from 2015 to 2017. All patients underwent serial DUS at 1 to 2 weeks and 1, 3, 6, and 12 months after UGFS. RESULTS: During the observation period, 268 patients were treated with UGFS, using physician compounded polidocanol foam 257 lower limbs of 196 patients (73%) with varicose veins who underwent DUS at 1 to 2 weeks after the last session of UGFS (inclusion time-point): 139 women and 57 men (mean age: 44.2 ± 12.2 years) with the following CEAP clinical class distribution: C2, 74.0%; C3, 20.0%; C4, 4.5%; and C5, 1.5%. NTO at the inclusion time-point occurred in 60 limbs (23.3%) of 57 patients (28.5%) and was symptomatic only in three limbs (1.2%). Most occlusions were localized in the untreated great saphenous vein trunk (n = 28) and the calf muscle veins (n = 23). Overall, 72%, 44%, 29%, and 10% of all limbs and 77%, 45%, 28%, and 12% of limbs with NTO were followed up by DUS at 1, 3, 6, and 12 months, respectively. There were no cases of thrombus progression or symptomatic venous thromboembolism (VTE). At six months, no deep vein occlusions persisted. CONCLUSIONS: The frequency of nontarget vein occlusion after UGFS revealed by serial DUS may be as high as 23.3%. These occlusions tend to resolve within six months and are not associated with symptomatic VTE.

Rivaroxaban in the treatment of upper extremity deep vein thrombosis: A single-center experience and review of the literature.

INTRODUCTION: Direct oral anticoagulants (DOACs) have become widely used to treat patients with venous thromboembolism (VTE), but evidence about their use in the treatment of upper extremity deep vein thrombosis (UEDVT) is lacking. OBJECTIVES: To assess rivaroxaban's efficacy and safety in the treatment of UEDVT. PATIENTS/METHODS: This was a single-center prospective observational study involving patients with their first UEDVT episode confirmed by duplex ultrasound scan. All patients initially received low-molecular-weight heparin for 1 to 2 days and then were switched to rivaroxaban for 3-6 months. The primary endpoint was any symptomatic episode of recurrent VTE. RESULTS: Thirty patients were included in the study, and all patients were followed for 6 months. There were no episodes of recurrent symptomatic venous thromboembolism or asymptomatic UEDVT. No episode of major bleeding was observed. Clinically relevant non-major bleeding occurred in two patients (6.7%, 95% confidence interval [CI]: 1.9-21.4%) with uterine bleeding and large skin hemorrhage. Minor bleeding was observed in two patients (6.7%, 95% CI: 1.9-21.4%) presenting with nasal and gingival bleeding. Recanalization of the upper extremity deep veins was observed in all affected limbs at three months, and it persisted up to 6 months. The signs of upper limb post-thrombotic syndrome (PTS) were found in four patients (13.4%; 95% CI: 5.4-29.8%), and the mean modified Villalta score was 2.1 ±â€¯1.9. CONCLUSION: Treatment of UEDVT with rivaroxaban, preceded by one to two days of LMWH, seems to be safe and effective.

Use of Micronized Purified Flavonoid Fraction Together with Rivaroxaban Improves Clinical and Ultrasound Outcomes in Femoropopliteal Venous Thrombosis: Results of a Pilot Clinical Trial.

INTRODUCTION: The aim of this study was to assess the impact of adding long-term micronized purified flavonoid fraction (MPFF) to standard treatment of femoropopliteal deep vein thrombosis (DVT). METHODS: This pilot, comparative, open-label study with blinded outcome assessor enrolled patients with a first episode of femoropopliteal DVT confirmed by duplex ultrasound scanning (DUS). All participants were randomly allocated to one of two treatment groups: (1) control that received a standard treatment with oral rivaroxaban, and (2) experimental that involved additional treatment with MPFF 1000 mg/day. Both drugs were used for 6 months. Patients were followed for the whole treatment period and underwent DUS every 2 months to determine the degree of recanalization by popliteal (PV), femoral vein (FV), and common femoral vein (CFV) compressibility. Thrombi extension were assessed by the modified Marder score. At the end of the follow-up period, patients were assessed with Villalta and venous clinical severity scales (VCSS). Patients with a Villalta score ≥ 5 were diagnosed with post-thrombotic syndrome (PTS). RESULTS: Sixty patients were randomized to the control or MPFF groups (n = 30 in each group). There were 40 men and 20 women with a mean age ± SD of 56.3 ± 13.4 years. Clinically unprovoked DVT was recognized in 65% of cases and left side localization in 45%. The mean baseline Marder score was 15.0 ± 4.8 and 11.1 ± 4.3 in the experimental and control groups, respectively (p = 0.002). At 6 months, the mean Villalta score in the MPFF group was significantly lower compared with control (2.9 ± 2.7 versus 5.8 ± 3.0; p < 0.0001). PTS was diagnosed in six patients (20%) and 17 patients (57%) in the experimental and control groups respectively (p = 0.007). A significant difference between the groups was also observed for the VCSS value (2.3 ± 1.9 versus 4.9 ± 1.9; p < 0001). After 6 months of treatment the Marder score decreased to 0.8 ± 1.6 and 2.8 ± 3.5 in the experimental and control groups, respectively (p = 0.006). In the MPFF group, there was a greater reduction in the Marder score (p < 0.0001) and more rapid rate of recanalization for the FV (p < 0.0001), with a non-significant trend for the CFV (p = 0.130) and PV (p = 0.204) compared with the control group. Full recanalization of the PV at 6 months was observed in 24 patients (80%) who had received MPFF, and only 17 patients (57%) in the control group (p = 0.095). CONCLUSION: The addition of MPFF to standard therapy for DVT in the form of oral rivaroxaban can reduce the incidence of PTS at 6 months in patients with proximal DVT and increase the speed of deep vein recanalization. FUNDING: Les Laboratoires Servier funded the article processing fees, editorial assistance, and open access fee for this manuscript.

Electrical calf muscle stimulation in patients with post-thrombotic syndrome and residual venous obstruction after anticoagulation therapy.

BACKGROUND: The aim of this study was to assess the impact of electrical calf muscle stimulation (EMS) on clinical and ultrasound outcomes in patients with post-thrombotic syndrome (PTS) and residual venous obstruction (RVO). METHODS: This was a prospective, comparative, non-randomized clinical trial involving patients who had completed a standard 6-month course of anticoagulation therapy for a first episode of unprovoked femoro-popliteal DVT and had signs of RVO in the affected veins and PTS as shown by a Villalta Score of >5. A blinded outcome assessor performed the ultrasound evaluations. A total of 60 patients in the age range from 40 to 86 years (mean 58.5±11.4) consisting of 38 men and 22 women were enrolled. They were divided into two groups of 30 participants each. Both groups (experimental and control) were treated by active walking, below-knee graduated compression stockings, and micronized purified flavonoid fraction. In the experimental group, EMS with «Veinoplus VI¼ device (three applications for 30 min every day) was also used. The patients were followed for 12 months with monthly DUS to reveal recurrent DVT and changes in RVO. The clinical criteria for treatment efficacy included changes in Villalta, VCSS and CIVIQ-20 scores. RESULTS: Recurrent DVT was found in seven of 30 patients in the control group and in zero of 30 patients in the experimental group (23.3% versus 0%, P=0.01). Through the follow-up period the degree of RVO decreased in all affected veins in both groups (P<0.01). The most significant changes were found in the popliteal vein; 60.8% decreased to 28.8% in the experimental group and 50.9% to 27.3% in the control group (P<0.01) with significant differences between the groups (P<0.01). VCSS, Villalta and CIVIQ-20 scores also significantly decreased in both groups (P<0.01). In the group with EMS, changes in the current parameters were more intensive (P<0.01). CONCLUSIONS: There is an ongoing process of deep vein recanalization during the 12 months after anticoagulant therapy cessation. Use of EMS in PTS treatment allows for reduction of recurrent DVT rates, increase the speed of deep vein recanalization and leads to additional improvement in the clinical PTS outcomes.

Validation of the Caprini risk assessment model for venous thromboembolism in high-risk surgical patients in the background of standard prophylaxis.

OBJECTIVE: We used the Caprini venous thromboembolism risk assessment score to prospectively evaluate if there was a correlation between the Caprini scores and the incidence of postoperative deep vein thrombosis (DVT) in high-risk surgical patients. A second objective was to determine whether patients at extremely high risk need a more effective prophylactic regimen. METHODS: This prospective multicenter observational study involved 140 high-risk patients who underwent abdominal (48%) or cranial and/or spinal (52%) surgery. All patients were assessed using the Caprini model and had a mean score of 9.5 ± 2.7 (range, 5-15). Our standard prophylaxis for venous thromboembolism consisted of above-knee graduated compression stockings with 18 to 21 mm Hg pressure and subcutaneous low-dose unfractionated heparin three times per day, starting on the first or second through the fifth postoperative day depending on the risk of bleeding. We performed a duplex ultrasound examination at baseline during the first 12 to 24 hours after surgery and then every 3 to 5 days until discharge to assess the lower limb venous system up to the inferior vena cava. The end point of the study was ultrasound verification of fresh DVT or pulmonary embolism (PE). Verification of PE was made in all cases of DVT using echocardiography, lung scintigraphy, combined single-photon emission computed tomography and X-ray computed tomography, or autopsy. RESULTS: Fresh postoperative DVT was found in 39 patients (28%). The incidence of DVT was 2% in patients with a Caprini score of 5 to 8, 26% in patients with scores of 9 to 11, and 65% in patients with scores of 12 to 15 (P for trend < .01). The risk for DVT was increased 18.7-fold for patients with scores of 9 to 11 and 98.4-fold for scores of 12 to 15 compared with patients with scores of 5 to 8. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.81-0.94) and a Caprini score of 11 was the cutoff point that provided the highest sensitivity combined with highest specificity. In the 77 patients with a score of <11, DVT occurred in 2 patients (3%). In contrast, in the 63 patients with a score of ≥ 11, DVT occurred in 37 patients (59%; P < .01). PE was found in 13 patients (9%) and confirmed with autopsy. In all cases, verified fresh DVT was the source of embolism. CONCLUSIONS: There was a significant correlation between Caprini scores and the incidence of postoperative DVT in high-risk surgical patients. A Caprini score of ≥ 11 can identify a subgroup of patients at extremely high risk. These patients need a more effective prophylactic regimen.