Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty

SummaryFour phase III studies compared oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA or TKA). A pooled analysis of these studies compared the effect of rivaroxaban with enoxaparin on symptomatic VTE plus all-cause mortality and bleeding events, and determined whether these effects were consistent in patient subgroups. Patients (N=12,729) aged ≥18 years and scheduled for elective THA or TKA received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily or 30 mg every 12 hours. The composite of symptomatic VTE and all-cause mortality, the prespecified primary efficacy endpoint and adjudicated bleeding events were analysed in the day 12 ± 2 active treatment pool. Subgroup analyses of these outcomes were performed over the total treatment period. In the day 12 ± 2 pool, the primary efficacy endpoint occurred in 29/6,183 patients receiving rivaroxaban (0.5%) versus 60/6,200 patients receiving enoxaparin (1.0%; p=0.001). Major bleeding occurred in 21 (0.3%) versus 13 (0.2%) patients, p=0.23; major plus non-major clinically relevant bleeding in 176 (2.8%) versus 152 (2.5%) patients, p=0.19; and any bleeding in 409 (6.6%) versus 384 (6.2%) patients, p=0.38, respectively. The reduction of symptomatic VTE plus all-cause mortality was consistent across prespecified subgroups (age, gender, body weight, creatinine clearance) in the total treatment period. Compared with enoxaparin regimens, rivaroxaban reduces the composite of symptomatic VTE and all-cause mortality after elective THA or TKA, with a small increase in bleeding, no signs of compromised liver safety and fewer serious adverse events.

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Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism: Pooled Analysis of Coagulation Biomarkers From Stars E-3 and Stars J-V.

Blood ◽

10.1182/blood.v120.21.2260.2260 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2260-2260

Author(s):

Takeshi Fuji ◽

Satoru Fujita ◽

Shintaro Tachibana ◽

Yohko Kawai

Keyword(s):

Venous Thromboembolism ◽

Factor Xa ◽

Pooled Analysis ◽

Phase Iii ◽

Bleeding Events ◽

Double Blind ◽

Once Daily ◽

Treatment Groups ◽

Post Operation ◽

D Dimer

Abstract Abstract 2260 Introduction: Edoxaban is an oral, once-daily, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. Two randomized, double-blind, double-dummy, phase III studies (STARS E-3 and STARS J-V) have been conducted to evaluate the efficacy and safety of edoxaban compared to enoxaparin for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) or total hip arthroplasty (THA). The objective of this pooled analysis was to investigate the effects of edoxaban on key coagulation biomarkers. Methods: Patients (N=1,326) undergoing TKA or THA in Japan and Taiwan were randomized to receive oral edoxaban 30 mg once daily (qd) or subcutaneous enoxaparin 2,000 IU twice daily (bid; equivalent to 20 mg bid) for 11–14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery, which is the standard of care in Japan. Blood samples were collected for coagulation biomarker measurements pre-operation, post-operation (pre-treatment, Day 0), Day 7 (prior to administration of the next dose) and completion day (Day 11–14). The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). The principal safety outcome was the incidence of major and clinically relevant non-major (CRNM) bleeding. Pharmacodynamic endpoints included key coagulation biomarkers such as D-dimer, prothrombin fragment F1+2 (F1+2) and soluble fibrin monomer complex (SFMC). Results: A total of 1,307 patients received at least 1 dose of edoxaban or enoxaparin. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 68 years, mean body weight was 58.8 kg and 83% of patients were female. Overall, edoxaban significantly reduced the incidence of the composite of symptomatic and asymptomatic DVT and PE compared with enoxaparin (5.1% vs 10.7%, P<0.001). The incidence of major and CRNM bleeding events was 4.6% vs 3.7% in the edoxaban and enoxaparin groups, respectively (P=0.427). For both treatment groups, D-dimer and SFMC levels were reduced at Day 7 compared to post-operation/pretreatment levels, then increased slightly by Day 11–14. Levels of F1+2 also decreased by Day 7 in both treatment groups and further decreased by Day 11–14. However, for each coagulation biomarker, levels were significantly lower in the edoxaban group compared to the enoxaparin group at both Day 7 and Day 11–14. (Table, P<0.001). Conclusion: Edoxaban 30 mg qd is superior to enoxaparin 20 mg bid in the prevention of VTE events with significant reduction of D-dimer, F1+2 and SFMC following TKA and THA. Disclosures: Fuji: Daiichi Sankyo: Consultancy; Bayer: Consultancy; Century Medical: Consultancy; Showa Ikakogyo: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Bayer: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Bayer: Consultancy; Toyama Chemical: Consultancy.

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Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial

Current Vascular Pharmacology ◽

10.2174/1570161116666180605090520 ◽

2019 ◽

Vol 17 (6) ◽

pp. 635-643

Author(s):

Kallirroi I. Kalantzi ◽

Ioannis V. Ntalas ◽

Vasileios G. Chantzichristos ◽

Maria E. Tsoumani ◽

Dimitrios Adamopoulos ◽

...

Keyword(s):

Clinical Trial ◽

Secondary Prevention ◽

Ischaemic Stroke ◽

Primary Efficacy ◽

Primary Efficacy Endpoint ◽

Bleeding Events ◽

Vascular Events ◽

Once Daily ◽

To Receive

Background: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. Objective: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. Methods: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. Results: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). Conclusion: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. : (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

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Safety of Rivaroxaban for Postoperative Venous Thromboembolism Prophylaxis Following Abdominal Body Contouring Surgery: 600 Patients

Aesthetic Surgery Journal ◽

10.1093/asj/sjaa177 ◽

2020 ◽

Cited By ~ 1

Author(s):

Vasileios Vasilakis ◽

Bill G Kortesis ◽

Gaurav Bharti ◽

Matthew H Isakson ◽

Joseph P Hunstad

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Body Contouring ◽

Bleeding Complications ◽

Bleeding Events ◽

Level Of Evidence ◽

Once Daily ◽

Postoperative Course ◽

Body Contouring Surgery ◽

Vte Prophylaxis

Abstract Background Reducing the incidence of venous thromboembolism (VTE) following abdominal body contouring surgery remains a top priority for patient safety. There is a lack of consensus regarding the optimal chemoprophylactic agent for postoperative VTE prophylaxis, and the role of oral anticoagulants warrants further investigation. Objectives The aim of this multisurgeon, single-institution study was to determine the safety and efficacy of a 7-day postoperative rivaroxaban regimen for VTE prophylaxis in abdominal body contouring surgery. Methods A retrospective chart review was performed of all patients who underwent abdominoplasty, circumferential body lift, fleur-de-lis panniculectomy, or circumferential fleur-de-lis panniculectomy at our surgical center from August 2014 to November 2019. A 7-day postoperative course of once-daily 10 mg rivaroxaban, starting on postoperative day 1, was administered to every patient unless there was a contraindication. The 2 primary endpoints were the incidence of VTE and bleeding events. Results A total of 600 patients were included in the study. There were no deaths. There were 4 (0.7%) incidents of VTE events: 2 (0.3%) patients suffered pulmonary embolus and 2 (0.3%) patients suffered a lower-extremity deep venous thrombosis. A total of 13 (2.2%) patients suffered complications related to bleeding. Of these, operative intervention for control and evacuation was required in 7 (1.2%) patients. Conclusions A 7-day postoperative course of once-daily rivaroxaban for VTE risk reduction in abdominal body contouring surgery is associated with a low incidence of VTE events and a low risk of bleeding complications. Level of Evidence: 4

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Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement

Thrombosis and Haemostasis ◽

10.1160/th10-02-0142 ◽

2010 ◽

Vol 104 (09) ◽

pp. 642-649 ◽

Cited By ~ 98

Author(s):

Alexander Cohen ◽

Bengt Eriksson ◽

David Puskas ◽

Minggao Shi ◽

Tomas Bocanegra ◽

...

Keyword(s):

Total Hip Replacement ◽

Hip Replacement ◽

Factor Xa ◽

Primary Efficacy ◽

Direct Factor ◽

Bleeding Events ◽

Once Daily ◽

Total Hip ◽

Efficacy Analysis ◽

Safety Outcome

SummaryEdoxaban is a new oral direct factor Xa inhibitor. The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing elective total hip replacement. A total of 903 patients were randomised to oral edoxaban 15, 30, 60 or 90 mg once daily or subcutaneous dalteparin once daily (initial dose 2,500 IU, subsequent doses 5,000 IU). Both drugs were begun 6–8 hours postoperatively and continued for 7–10 days, when bilateral venography was performed. The primary efficacy endpoint was the incidence of total VTE, which included proximal and/or distal deep-vein thrombosis (DVT) by venography or symptomatic, objectively confirmed DVT or pulmonary embolism during the treatment period. The primary safety outcome was the incidence of the composite of major and clinically relevant non-major bleeding. All venograms and bleeding events were reviewed by a central independent adjudication committee blinded as to treatment allocation. Of the 903 patients randomised, 776 were evaluable for the primary efficacy analysis. The incidences of VTE were 28.2%, 21.2%, 15.2%, and 10.6% in patients receiving edoxaban 15, 30, 60 and 90 mg, respectively, compared with 43.8% in the dalteparin group (p<0.005 ). There was a statistically significant (p<0.001) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE. The incidence of clinically relevant bleeding was low and similar across the groups. Oral edoxaban once daily is effective for preventing VTE after total hip replacement.

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Prevention of Venous Thromboembolism after Acute Ischemic Stroke with Enoxaparin Versus Unfractionated Heparin and the Impact of Stroke Severity.

Blood ◽

10.1182/blood.v108.11.713.713 ◽

2006 ◽

Vol 108 (11) ◽

pp. 713-713 ◽

Cited By ~ 2

Author(s):

David G. Sherman ◽

Gregory W. Albers ◽

Christopher Bladin ◽

Min Chen ◽

Cesare Fieschi ◽

...

Keyword(s):

Ischemic Stroke ◽

Venous Thromboembolism ◽

Acute Ischemic Stroke ◽

Stroke Severity ◽

Primary Efficacy ◽

Primary Efficacy Endpoint ◽

Stroke Patients ◽

Nihss Score ◽

Vte Prophylaxis ◽

Clinically Significant

Abstract Background: Venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is recommended in acute ischemic stroke patients, but most studies comparing LMWH and UFH are limited in methodology or sample size. The PREVAIL study was designed to assess the superiority of enoxaparin over UFH for VTE prophylaxis in acute ischemic stroke patients and to evaluate efficacy and safety according to stroke severity. Methods: Patients with acute ischemic stroke, confirmed by CT scan, and unable to walk unassisted due to motor impairment of the leg were enrolled in this prospective, open-label, parallel group, multicenter study. Patients from 15 countries were randomized within 48 h of stroke symptoms to receive enoxaparin 40 mg SC qd or UFH 5000 IU SC q12h for 10±4 days. Patients were stratified by NIH Stroke Scale score (NIHSS; severe ≥14, less severe <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep-vein thrombosis (DVT), symptomatic pulmonary embolism (PE), or fatal PE during treatment. DVT was confirmed primarily by venography, or ultrasonography when venography was not practical. PE was confirmed by VQ or CT scan, or angiography. Primary safety endpoints included clinically significant intracranial and major extracranial bleeding. Results: 1762 acute ischemic stroke patients were randomized. Characteristics were similar between groups; mean age was 66.0±12.9 yrs, mean NIHSS score was 11.3. In the efficacy population, enoxaparin (n=666) and UFH (n=669) were given for a mean of 10.5±3.2 days. Enoxaparin resulted in a 43% relative reduction in the risk of the primary efficacy endpoint compared with UFH (10.2% vs 18.1%; RR 0.57; 95% CI 0.44–0.76; p=0.0001, adjusted for NIHSS score). Incidences of VTE events are shown in Table 1. Reductions in the primary endpoint remained significant in patients with a NIHSS score ≥14 (16.3% vs 29.7%, p=0.0036) and <14 (8.3% vs 14.0%, p=0.0043). The composite of clinically significant intracranial and major extracranial bleeding was low and not significantly different between groups (Table 1). Conclusion: Enoxaparin 40 mg qd is superior to UFH q12h for reducing the risk of VTE in acute ischemic stroke patients, with no significant difference in clinically relevant bleeding. The reduction in VTE risk was consistent in patients with a NIHSS score ≥14 or <14. Table 1: Incidence of VTE and bleeding Endpoint Enoxaparin n/N (%, 95% CI) UFH n/N (%, 95% CI) *P<0.001 Symptomatic VTE 2/666 (0.3, 0.0–0.7) 6/669 (0.9, 0.2–1.6) Proximal DVT 30/666 (4.5, 2.9–6.1) 64/669 (9.6, 7.3–11.8)* Distal DVT 44/666 (6.6, 4.7–8.5) 85/669 (12.7, 10.2–15.2)* PE 1/666 (0.2, 0.0–0.4) 6/669 (0.9, 0.2–1.6) Composite of major extracranial and clinically significant intracranial bleeding 11/877 (1.3, 0.5–1.9) 6/872 (0.7, 0.1–1.2)

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Once-Daily Oral Rivaroxaban Compared with Subcutaneous Enoxaparin Every 12 Hours for Thromboprophylaxis after Total Knee Replacement: RECORD4

Blood ◽

10.1182/blood.v112.11.35.35 ◽

2008 ◽

Vol 112 (11) ◽

pp. 35-35 ◽

Cited By ~ 3

Author(s):

Alexander GG Turpie ◽

Kenneth A. Bauer ◽

Bruce Davidson ◽

Michael Gent ◽

Louis Kwong ◽

...

Keyword(s):

Total Knee Replacement ◽

Knee Replacement ◽

Major Bleeding ◽

Phase Iii ◽

Primary Efficacy ◽

Once Daily ◽

Intention To Treat ◽

Protocol Population ◽

Total Knee ◽

Treat Population

Abstract Rivaroxaban is an oral, direct Factor Xa inhibitor that has been evaluated in the RECORD phase III clinical trial program for the prevention of venous thromboembolism (VTE) in major orthopaedic surgery. RECORD3 (Lassen M, et al. N Engl J Med2008;358:2776–2786) showed that oral rivaroxaban 10 mg once daily (od) given post-operatively significantly reduced VTE after total knee replacement (TKR), compared with subcutaneous (s.c.) enoxaparin 40 mg od initiated pre-operatively, with similar rates of bleeding. RECORD4 was designed to determine the efficacy and safety of rivaroxaban compared with enoxaparin 30 mg administered twice daily after TKR. Patients (N=3,148) were randomized to receive either oral rivaroxaban 10 mg od (initiated 6–8 hours after surgery) or s.c. enoxaparin 30 mg every 12 hours (initiated 12 to 24 hours after surgery) for 10 to 14 days. Patients underwent mandatory, bilateral venography between day 11 and day 15. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality up to day 17. The primary efficacy analysis was a test for non-inferiority in the per-protocol population (n=1,702), followed by a test for superiority in the modified intention-to-treat population (n=1,924) (if non-inferiority was established in the per-protocol population). The main secondary efficacy endpoint was major VTE: the composite of proximal DVT, non-fatal PE, and VTE-related death. Treatment-emergent major bleeding observed no later than two days after the last intake of study was the main safety endpoint. The results are shown in the table. Rivaroxaban significantly reduced the incidence of the primary efficacy outcome compared with enoxaparin (6.9% vs 10.1%, respectively; p=0.012; relative risk reduction 31%). Rivaroxaban was non-inferior to enoxaparin for the prevention of major VTE in the per-protocol population (p<0.001). The observed incidences of major VTE and symptomatic VTE in those receiving rivaroxaban or enoxaparin were 1.2% vs 2.0% (p=0.124), and 0.7% vs 1.2% (p=0.187), respectively, and the rates of major bleeding were 0.7% vs 0.3% (p=0.110) respectively, and major and clinically relevant non-major bleeding 3.0% vs 2.3% (p=0.179) in the rivaroxaban and enoxaparin treated groups, respectively. The data demonstrate that rivaroxaban has superior efficacy to enoxaparin 30 mg administered every 12 hours for the prevention of VTE after TKR, without significantly increasing the risk of bleeding. Endpoint Rivaroxaban10 mg od % (n/N) Enoxaparin30 mg q12h % (n/N) p-value for differenced aModified intention-to-treat population bModified intention-to-treat population valid for major VTE analysis cSafety population dCalculated for the absolute risk difference DVT, non-fatal PE, and all-cause mortalitya 6.9% (67/965) 10.1% (97/959) 0.012 Major VTEb 1.2% (13/1,122) 2.0% (22/1,112) 0.124 Symptomatic VTEc 0.7% (11/1,526) 1.2% (18/1,508) 0.187 Major bleedingc 0.7% (10/1,526) 0.3% (4/1,508) 0.110 Any non-major bleedingc 10.2% (155/1,526) 9.2% (138/1,508) – Major and clinically relevant non-major bleedingc 3.0% (46/1526) 2.3% (34/1,508) 0.179

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A Pooled Analysis of Four Pivotal Studies of Rivaroxaban for the Prevention of Venous Thromboembolism after Orthopaedic Surgery: Effects of Specified Co-Medications.

Blood ◽

10.1182/blood.v112.11.1986.1986 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1986-1986

Author(s):

Bengt Eriksson ◽

Alexander GG Turpie ◽

Michael Rud Lassen ◽

Ajay K Kakkar ◽

Frank Misselwitz ◽

...

Keyword(s):

Placebo Group ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Medication Use ◽

Pooled Analysis ◽

Phase Iii ◽

Bleeding Events ◽

Time Periods ◽

Rate Ratios ◽

Over Time

Abstract RECORD is a pivotal clinical trial program investigating rivaroxaban – an oral, direct Factor Xa inhibitor – for the prevention of venous thromboembolism (VTE) following elective total hip and knee replacement (THR and TKR). The four multinational, randomized, double-blind, double-dummy phase III studies (RECORD1, 2, 3 and 4) in patients undergoing THR or TKR surgery, comparing rivaroxaban with enoxaparin 40 mg once daily (od) or 30 mg twice daily (bid), have been completed. Patients (N=12,729) were randomized to receive oral rivaroxaban 10 mg od starting 6–8 hours after surgery, or subcutaneous enoxaparin 40 mg od starting the evening before surgery (RECORD1–3) or 30 mg bid starting 12–24 hours after wound closure or adequate hemostasis (RECORD4). Those undergoing THR received rivaroxaban or enoxaparin for 31–39 days in RECORD1, and rivaroxaban for 31–39 days or enoxaparin for 10–14 days followed by placebo in RECORD2. In RECORD3 and 4 (TKR), prophylaxis was for 10–14 days. A pooled analysis of the results of all four RECORD studies evaluated the effect of rivaroxaban on the composite of symptomatic VTE and death, and bleeding. The aim of the present subgroup analysis was to investigate potential drug–drug interactions with specified co-medications, by describing the risk of on-treatment bleeding in the total study duration pool of all four RECORD studies. The co-medications investigated were non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA), which are commonly used pain medications known to have a pharmacodynamic effect on bleeding. There was no restriction on the choice of specific drug or on the dose of ASA in the study protocols. These pre-specified analyses focused on on-treatment, adjudicated bleeding events – any bleeding, and the composite of major bleeding, and clinically relevant non-major bleeding – after the first tablet intake (rivaroxaban or matching placebo) and up to 2 days after the last dose of medication. Co-medication use was considered a time-dependent covariate, and relative bleeding rates with and without the co-medication were calculated for the rivaroxaban and enoxaparin/placebo groups separately. The time relative to surgery (day of surgery was day 1) was stratified into three time periods (days 1–3, days 4–7, and day 7 onwards), based on the consideration that the risk of a first bleeding event decreases over time after surgery, and because the prevalence of co-medication use can vary over time. Bleeding rates were recorded for each of these time periods over the at-risk period, which extended from the day of surgery until the last day of study medication intake +2 days or until event onset (recurrent bleeds were not included in the analyses). Rate ratios were derived using stratified Mantel–Haenszel methods. The ratios of the bleeding rate for exposed versus unexposed patient-days in the rivaroxaban group were compared with the corresponding rate ratio for the enoxaparin/placebo group for bleeding events. The concomitant use of ASA in the rivaroxaban groups showed rate ratios similar to those obtained in the enoxaparin/placebo group, for all bleeding endpoints. Rate ratios for bleeding endpoints were also similar between the rivaroxaban and the enoxaparin/placebo groups with concomitant use of NSAIDs. This RECORD1–4 subanalysis indicates that the use of these co-medications does not increase bleeding risk in patients taking rivaroxaban, compared with enoxaparin

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The Ultra-Low-Molecular-Weight Heparin Semuloparin for Prevention of Venous Thromboembolism In Patients Undergoing Major Abdominal Surgery

Blood ◽

10.1182/blood.v116.21.188.188 ◽

2010 ◽

Vol 116 (21) ◽

pp. 188-188 ◽

Cited By ~ 8

Author(s):

Ajay K. Kakkar ◽

Giancarlo Agnelli ◽

William D. Fisher ◽

Daniel George ◽

Patrick Mouret ◽

...

Keyword(s):

Abdominal Surgery ◽

Board Of Directors ◽

Research Funding ◽

Major Abdominal Surgery ◽

Low Molecular Weight ◽

Primary Efficacy ◽

Advisory Committees ◽

Once Daily ◽

All Cause Mortality ◽

Bayer Healthcare

Abstract Abstract 188 Background/Aim: Venous thromboembolism (VTE) remains a common and potentially fatal complication of major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin (ULMWH) with high anti-factor Xa and residual anti-factor IIa activities currently under development for prevention of VTE. We have conducted a study to assess the efficacy and safety of semuloparin compared to enoxaparin for the prevention of VTE in patients undergoing major abdominal surgery. Material and methods: SAVE-ABDO is a multinational, randomized, double-blind phase III study of patients undergoing major abdominal or pelvic operation. Patients were randomized to receive either once-daily enoxaparin 40 mg commenced pre-operatively or semuloparin 20 mg commenced post-operatively, both agents continued for 7–10 days. Patients were eligible for inclusion if they were aged > 60 years, had undergone major surgery in the peritoneal or the retroperitoneal space, and/or pelvis under general anesthesia lasting more than 45 minutes. For patients under the age of 60 years old, an additional risk factor (history of VTE, body mass index ≥ 30 kg/m2, chronic heart failure, chronic respiratory failure, inflammatory bowel disease, or operation for malignancy) was required. For patients with severe renal impairment, defined as a creatinine clearance < 30 mL/min, the dose of semuloparin was reduced to 10 mg once-daily, and that of enoxaparin to 20 mg once-daily. Randomization was stratified by indication for operation (cancer versus non-cancer), renal function (creatinine clearance ≥ or < 30 mL/min), and geographic region. Mandatory bilateral venography was performed between day 7 and 11. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. Secondary efficacy endpoints included the composite of any VTE and VTE-related mortality, and the composite of any proximal DVT, symptomatic distal DVT, non-fatal pulmonary embolism, and all-cause mortality. The main safety endpoint was major bleeding, with main secondary safety endpoints of clinically-relevant non-major (CRNM) bleeding, and the composite of major and CRNM bleeding. All study endpoints were independently and blinded adjudicated. The non-inferiority will be reached if the upper limit of the confidence interval of the odds ratio for the primary analysis is < 1.25. If the non-inferiority is demonstrated the superiority will be tested using a stratified exact test on the primary efficacy endpoint. Results: 4414 patients were randomized between May 2008 and June 2010. The mean age was 61 years (±13 years) and 57% of subjects were male. 81% of patients underwent an operation for malignant disease. The majority of patients underwent gastro-intestinal procedures, with 59% having colon or colo-rectal surgery, and 20% gastric surgery. Final data will be available for presentation at the meeting. Disclosures: Kakkar: Bayer Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; sanofi-aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Agnelli:sanofi-aventis: Research Funding. Fisher:sanofi-aventis: Honoraria, Research Funding; Bayer Healthcare: Honoraria, Research Funding; Takeda Pharmaceuticals: Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees. George:sanofi-aventis: Honoraria. Mouret:Bayer Healthcare: Consultancy, Honoraria; sanofi-aventis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Lassen:Astellas Pharma Europe: Consultancy; Bayer Healthcare: Consultancy; Bristol-Myers Squibb: Consultancy; GlaxoSmithKline: Consultancy; Merck Serono: Consultancy; Pfizer: Consultancy; sanofi-aventis: Consultancy. Mismetti:sanofi-aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria; Boehringer-Ingelheim: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria. Murphy:sanofi-aventis: Employment. Turpie:Astellas Pharma Europe: Consultancy; Bayer Healthcare: Consultancy; Portola Pharma: Consultancy; sanofi-aventis: Consultancy.

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Prospective application of a risks-adjusted antithrombotic protocol in elderly patients treated with the last generation of everolimus-eluting stents. The SIERRA-75 (EPIC-05) registry

European Heart Journal ◽

10.1093/eurheartj/ehab724.2116 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

J M De La Torre Hernandez ◽

R Lopez Palop ◽

J M Jimenez Mazuecos ◽

P Carrillo Saez ◽

A Gutierrez Barrios ◽

...

Keyword(s):

Elderly Patients ◽

Stent Thrombosis ◽

Control Group ◽

Primary Efficacy ◽

Primary Efficacy Endpoint ◽

Bleeding Events ◽

Funding Sources ◽

Safety Endpoint ◽

Adjusted Model ◽

Primary Safety Endpoint

Abstract Background Elderly patients show a higher incidence of ischemic and bleeding events after PCI. Purpose We sought to investigate clinical outcomes in elderly patients revascularized with last generation everolimus-eluting stent (EES) treated with antithrombotic strategies guided by bleeding and ischemic risks. Methods Prospective multicenter registry including patients over 75 years revascularized with EES and subsequent antithrombotic therapy guided according to a protocol based on clinical presentation, PCI complexity and the PRECISE DAPT score. The primary safety endpoint was a composite of cardiac death, myocardial infarction and definitive/probable stent thrombosis and the primary efficacy endpoint was TLR. An historical matched group of patients treated with current drug eluting stents other than EES was used as control. Results Finally, 1,064 patients were included, 80.8±4.2 years, 36.6% women, 72% ACS and 53.6% complex PCI. Primary safety endpoint was met in 6.2% and primary efficacy endpoint in 1.5%. Bleeding BARC 2–5 was reported in 7.8% and definite or probable stent thrombosis in 1.3%. The multivariable adjusted model showed no significant association of the prescribed short/long therapies with any endpoint. No stent thrombosis were reported in the subgroup with shorter DAPT duration. As compared to control group, bleeding BARC 2–5 was significantly lower in SIERRA-75 group (7.4% vs 10.2%, p=0.04) as well as the composite of MACE and bleeding (14.3% vs 18.5%, p=0.02). Conclusions In elderly population the use of last generation EES along with a predefined risks-adjusted antithrombotic regimen seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Abbott Laboratories

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Dabigatran Etexilate or Warfarin in the Treatment of Acute Venous Thromboembolism in Western European Patients: A Pooled Analysis of RE-COVER® and RE-COVER II™

Blood ◽

10.1182/blood.v126.23.4730.4730 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4730-4730

Author(s):

Sebastian Schellong ◽

Henry Eriksson ◽

Samuel Z. Goldhaber ◽

Martin Feuring ◽

Stefan Hantel ◽

...

Keyword(s):

Venous Thromboembolism ◽

Research Funding ◽

Dabigatran Etexilate ◽

Primary Efficacy ◽

Bleeding Events ◽

Primary Efficacy Outcome ◽

Efficacy Outcome ◽

Safety Outcomes ◽

Western European ◽

Acute Venous Thromboembolism

Abstract Introduction: In the RE-COVER®/RE-COVER II™ global randomized trials investigating the treatment of acute venous thromboembolism (VTE), efficacy and safety outcomes of dabigatran etexilate (dabigatran) versus warfarin were compared. This sub-analysis of pooled RE-COVER®/RE-COVER II™ data compares the safety and efficacy of dabigatran versus warfarin in the Western European sub-population. Methods: In the RE-COVER®/RE-COVER II™ trials, patients with acute VTE, initially receiving parenteral anticoagulation, were randomized to warfarin (INR 2-3) or dabigatran (150 mg twice daily) for 6 months and followed up for 30 days. The primary efficacy outcome was recurrent, symptomatic VTE/VTE-related death. Safety outcomes were major bleeding events (MBEs), a composite of MBEs or clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeding during the 6-month, oral-only treatment period. All outcomes were centrally adjudicated. Data from the Western European sub-population were analyzed using a Cox regression model with factor treatment stratified by study, assuming different baseline hazards per study. Results: This sub-analysis included 1239 patients for the efficacy analysis (dabigatran n = 613; warfarin n = 626) and 1192 patients for safety (dabigatran n = 588; warfarin n = 604) from all 13 Western European countries participating in the RE-COVER®/RE-COVER II™ trials. For the primary efficacy outcome, the rate of VTE/VTE-related death in patients receiving dabigatran was 2.1% (n = 13) compared with 2.9% (n = 18) in those receiving warfarin. However, this difference did not reach statistical significance (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.36-1.5). Of the safety outcomes, rates of MBEs were similar between both treatment groups (1.4% for dabigatran [n = 8] and 1.3% for warfarin [n = 8]; HR 1.02; 95% CI, 0.38-2.71). Rates of MBEs/CRBEs were significantly lower in patients receiving dabigatran than in those receiving warfarin at 5.1% (n = 30) and 9.4% (n = 57), respectively (HR 0.52; 95% CI, 0.34-0.82). Any bleeding events were also statistically lower in the dabigatran group (17.5%; n = 103) compared with warfarin (23.8%; n = 144) (HR 0.7; 95% CI, 0.54-0.90). Conclusions: In this Western European sub-analysis of pooled data from the RE-COVER®/ RE-COVER II™ trials, dabigatran was as effective as warfarin in the treatment of acute VTE. There was a significant reduction in MBE/CRBE and in any bleeding events in the dabigatran treatment group. Disclosures Schellong: Boehringer Ingelheim: Consultancy. Eriksson:Boehringer Ingelheim: Consultancy. Goldhaber:Boehringer Ingelheim: Consultancy, Research Funding. Feuring:Boehringer Ingelheim: Employment. Hantel:Boehringer Ingelheim Pharma GmbH and Co. KG: Employment. Kreuzer:Boehringer Ingelheim Pharma GmbH and Co. KG: Employment. Schulman:Boehringer Ingelheim: Honoraria, Research Funding; Bayer: Honoraria; Baxter: Honoraria; Octapharma: Research Funding. Kakkar:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding.

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