ASH 2011

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.

SAN DIEGO – Insulinlike growth factor I level was not useful as a marker of growth hormone deficiency or altered body composition in a retrospective review of a large cohort of adult survivors of childhood cancers.

Late cancer treatment–related complications – metabolic syndrome, osteogenic side effects, thyroid dysfunction, and growth hormone deficiency – are increasing as a result of increased childhood cancer survivorship; 1 in 640 young adults is now a survivor of childhood cancer, she said.

Insulinlike growth factor I (IGF-I) is often used as a marker for growth hormone deficiency, said Dr. Blijdorp of the department of pediatric oncology at Erasmus University, Rotterdam, the Netherlands. Low IGF-I has been associated with a high body mass index and high visceral fat percentage, she said. Because BMI, dual x-ray absorptiometry (DXA), and waist-hip ratio are limited in their ability to determine body composition, "it would be useful to have an easy-to-measure serum marker, such as IGF-I, that predicts alterations in body composition, she added.

Dr. Blijdorp and her associates retrospectively reviewed 610 adult childhood cancer survivors who were treated at the university. Their median age at diagnosis was 6 years and the median follow-up time was 18 years. The researchers reviewed IGF-I z scores, anthropometrical measures, growth hormone–stimulation tests in patients with clinical suspicion of growth hormone deficiency, and measures of body composition on DXA.

About 30% of the patients had leukemia. Of the 610 survivors, 158 had cranial irradiation. A history of cranial irradiation was associated with a higher incidence of metabolic syndrome, with an increased BMI, waist-hip ratio, visceral fat percentage, and total body fat percentage, as well as lower lean body mass, Dr. Karin Blijdorp said at the annual meeting of the American Society of Hematology.

Significantly lower IGF-I z-scores (P less than .001) were noted in the acute leukemia survivors who had cranial irradiation (25 Gy; range, 24-25 Gy) and the brain tumor survivors who had local irradiation (42 Gy; range, 35-54 Gy). Compared with survivors who did not undergo cranial irradiation, survivors who underwent cranial irradiation also had lower height standard deviation scores (P less than .001), higher BMI (P less than .01), higher waist-hip ratios (P less than .001), higher visceral fat percentages (P less than .001), higher total body fat percentages (P less than .001), and lower lean body mass (P less than .001).

IGF-I was not strongly correlated with BMI (r = 0.12; P = .04), waist-hip ratio (r = 0.15; P = .01), total fat percentage (r = 0.14; P = .02), and lean body mass (r = 0.15; P = .01).

Among survivors who had low IGF-I levels and received growth hormone stimulation, IGF-I z scores did not did not significantly differ between those with and without severe growth hormone deficiency (P = .39).

Dr. Blijdorp said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Insulinlike growth factor I level was not useful as a marker of growth hormone deficiency or altered body composition in a retrospective review of a large cohort of adult survivors of childhood cancers.

Late cancer treatment–related complications – metabolic syndrome, osteogenic side effects, thyroid dysfunction, and growth hormone deficiency – are increasing as a result of increased childhood cancer survivorship; 1 in 640 young adults is now a survivor of childhood cancer, she said.

Insulinlike growth factor I (IGF-I) is often used as a marker for growth hormone deficiency, said Dr. Blijdorp of the department of pediatric oncology at Erasmus University, Rotterdam, the Netherlands. Low IGF-I has been associated with a high body mass index and high visceral fat percentage, she said. Because BMI, dual x-ray absorptiometry (DXA), and waist-hip ratio are limited in their ability to determine body composition, "it would be useful to have an easy-to-measure serum marker, such as IGF-I, that predicts alterations in body composition, she added.

Dr. Blijdorp and her associates retrospectively reviewed 610 adult childhood cancer survivors who were treated at the university. Their median age at diagnosis was 6 years and the median follow-up time was 18 years. The researchers reviewed IGF-I z scores, anthropometrical measures, growth hormone–stimulation tests in patients with clinical suspicion of growth hormone deficiency, and measures of body composition on DXA.

About 30% of the patients had leukemia. Of the 610 survivors, 158 had cranial irradiation. A history of cranial irradiation was associated with a higher incidence of metabolic syndrome, with an increased BMI, waist-hip ratio, visceral fat percentage, and total body fat percentage, as well as lower lean body mass, Dr. Karin Blijdorp said at the annual meeting of the American Society of Hematology.

Significantly lower IGF-I z-scores (P less than .001) were noted in the acute leukemia survivors who had cranial irradiation (25 Gy; range, 24-25 Gy) and the brain tumor survivors who had local irradiation (42 Gy; range, 35-54 Gy). Compared with survivors who did not undergo cranial irradiation, survivors who underwent cranial irradiation also had lower height standard deviation scores (P less than .001), higher BMI (P less than .01), higher waist-hip ratios (P less than .001), higher visceral fat percentages (P less than .001), higher total body fat percentages (P less than .001), and lower lean body mass (P less than .001).

IGF-I was not strongly correlated with BMI (r = 0.12; P = .04), waist-hip ratio (r = 0.15; P = .01), total fat percentage (r = 0.14; P = .02), and lean body mass (r = 0.15; P = .01).

Among survivors who had low IGF-I levels and received growth hormone stimulation, IGF-I z scores did not did not significantly differ between those with and without severe growth hormone deficiency (P = .39).

Dr. Blijdorp said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Insulinlike growth factor I level was not useful as a marker of growth hormone deficiency or altered body composition in a retrospective review of a large cohort of adult survivors of childhood cancers.

Late cancer treatment–related complications – metabolic syndrome, osteogenic side effects, thyroid dysfunction, and growth hormone deficiency – are increasing as a result of increased childhood cancer survivorship; 1 in 640 young adults is now a survivor of childhood cancer, she said.

Insulinlike growth factor I (IGF-I) is often used as a marker for growth hormone deficiency, said Dr. Blijdorp of the department of pediatric oncology at Erasmus University, Rotterdam, the Netherlands. Low IGF-I has been associated with a high body mass index and high visceral fat percentage, she said. Because BMI, dual x-ray absorptiometry (DXA), and waist-hip ratio are limited in their ability to determine body composition, "it would be useful to have an easy-to-measure serum marker, such as IGF-I, that predicts alterations in body composition, she added.

Dr. Blijdorp and her associates retrospectively reviewed 610 adult childhood cancer survivors who were treated at the university. Their median age at diagnosis was 6 years and the median follow-up time was 18 years. The researchers reviewed IGF-I z scores, anthropometrical measures, growth hormone–stimulation tests in patients with clinical suspicion of growth hormone deficiency, and measures of body composition on DXA.

About 30% of the patients had leukemia. Of the 610 survivors, 158 had cranial irradiation. A history of cranial irradiation was associated with a higher incidence of metabolic syndrome, with an increased BMI, waist-hip ratio, visceral fat percentage, and total body fat percentage, as well as lower lean body mass, Dr. Karin Blijdorp said at the annual meeting of the American Society of Hematology.

Significantly lower IGF-I z-scores (P less than .001) were noted in the acute leukemia survivors who had cranial irradiation (25 Gy; range, 24-25 Gy) and the brain tumor survivors who had local irradiation (42 Gy; range, 35-54 Gy). Compared with survivors who did not undergo cranial irradiation, survivors who underwent cranial irradiation also had lower height standard deviation scores (P less than .001), higher BMI (P less than .01), higher waist-hip ratios (P less than .001), higher visceral fat percentages (P less than .001), higher total body fat percentages (P less than .001), and lower lean body mass (P less than .001).

IGF-I was not strongly correlated with BMI (r = 0.12; P = .04), waist-hip ratio (r = 0.15; P = .01), total fat percentage (r = 0.14; P = .02), and lean body mass (r = 0.15; P = .01).

Among survivors who had low IGF-I levels and received growth hormone stimulation, IGF-I z scores did not did not significantly differ between those with and without severe growth hormone deficiency (P = .39).

Dr. Blijdorp said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who receive heparin bridging during an interruption of oral anticoagulation appear to be at a 5.4-fold increased risk of overall bleeding and a 3.6-fold increased risk of major bleeding, without a reduction in risk of thromboembolic events.

Those are key findings from a systematic review and meta-analysis of recently published medical literature presented by Dr. Jovana Yudin at the annual meeting of the American Society of Hematology.

Antithrombotic and thrombolytic therapy guidelines published by the American College of Chest Physicians in 2008 recommended bridging according to an individualized approach (Chest 2008;133[suppl. 6]:299S-339S).

"They suggested bridging according to patients’ bleeding and thromboembolic risk," said Dr. Yudin, a fellow in the hematology residency program at McMaster University, Hamilton, Ont. "Within the last decade, several new studies have been published using periprocedural bridging. In these studies, low-molecular-weight heparin has been used with increased frequency. However, optimal strategies for bridging remain unclear. Our objective was to do a systematic review and meta-analysis of bridging trials published in the last decade to look at thromboembolic risk as well as bleeding risk."

Dr. Yudin and her associates searched the MEDLINE, EMBASE, and Cochrane Collaboration databases for systematic reviews and meta-analyses of studies published between Jan. 1, 2001, and July 31, 2010, that examined bleeding and thromboembolic events in patients receiving bridging therapy during temporary oral anticoagulation interruption for elective surgical or invasive procedures. Studies were excluded if the reporting of thromboembolic or bleeding outcomes was unclear, or if they focused exclusively on patients with renal failure (ASH 2011; abstract 545). All studies were reviewed by two independent investigators.

The researchers identified and screened 1,164 studies for review. Of these, 35 studies that included 7,169 bridged patients were selected for the final review. Most of the studies (33) were observational, and only two were randomized. The median follow-up was 30 days.

The most common indication for anticoagulation was atrial fibrillation (44%), followed by mechanical valve (24%), prior venous thromboembolism (22%), and other (10%).

The most common preoperative strategy was to discontinue oral anticoagulation more than 3 days in advance. Low-molecular-weight heparin was most commonly used, both preoperatively and postoperatively.

Dr. Yudin reported that thromboembolic events, which were primarily arterial in nature, occurred in 73 of the 7,169 patients (mean rate, 0.96%). The mean rate of overall bleeding was 13.01%, whereas the mean rate of major bleeding was 4.32%.

Eight of the studies included in the final analysis had control groups from which the researchers were able to pull data to determine an odds ratio for thromboembolism with bridging vs. no bridging. These studies included 1,691 bridged patients and 3,493 nonbridged patients. The odds ratio for thromboembolic events was 0.80, with a 95% confidence interval (CI) of 0.42-1.54, "suggesting no risk reduction for thromboembolic events with heparin or low-molecular-weight bridging," Dr. Yudin said. "There was also no difference between these two groups in the risk for arterial or venous thromboembolism."

To determine the risk of overall bleeding, the researchers pulled data from 13 studies that included control groups. These studies included 1,935 bridged patients and 5,160 nonbridged patients. The odds ratio for overall bleeding with bridging was 5.40 (95% CI, 3.00-9.74). "This suggested an increased risk of overall bleeding with bridging anticoagulation, but there was significant heterogeneity noted across these studies."

For major bleeding, five studies with control groups were assessed. These included 1,397 bridged patients and 2,104 nonbridged patients. The odds ratio for major bleeding was 3.60 (95% CI, 1.52-8.50), "again suggesting an increased risk in major bleeding with bridging," she said. "There was significant heterogeneity noted across studies."

Dr. Yudin acknowledged that the review had certain limitations: Most of the studies included in the analysis were observational, and only about a third had control groups. "Our control groups consisted largely of low-thromboembolic-risk patients, or patients who were not chronically on vitamin K antagonists, suggesting that they had a different risk profile for thromboembolism than many of the bridged patients," she said.

The findings "underline the need for studies of higher [methodological] quality in periprocedural bridging," she concluded. "It also tells us that there is a need for standardized definitions in terms of outcomes. We suspect that much of our heterogeneity had to do with varying definitions for outcomes such as major bleeding."

Dr. Yudin said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who receive heparin bridging during an interruption of oral anticoagulation appear to be at a 5.4-fold increased risk of overall bleeding and a 3.6-fold increased risk of major bleeding, without a reduction in risk of thromboembolic events.

Those are key findings from a systematic review and meta-analysis of recently published medical literature presented by Dr. Jovana Yudin at the annual meeting of the American Society of Hematology.

Antithrombotic and thrombolytic therapy guidelines published by the American College of Chest Physicians in 2008 recommended bridging according to an individualized approach (Chest 2008;133[suppl. 6]:299S-339S).

"They suggested bridging according to patients’ bleeding and thromboembolic risk," said Dr. Yudin, a fellow in the hematology residency program at McMaster University, Hamilton, Ont. "Within the last decade, several new studies have been published using periprocedural bridging. In these studies, low-molecular-weight heparin has been used with increased frequency. However, optimal strategies for bridging remain unclear. Our objective was to do a systematic review and meta-analysis of bridging trials published in the last decade to look at thromboembolic risk as well as bleeding risk."

Dr. Yudin and her associates searched the MEDLINE, EMBASE, and Cochrane Collaboration databases for systematic reviews and meta-analyses of studies published between Jan. 1, 2001, and July 31, 2010, that examined bleeding and thromboembolic events in patients receiving bridging therapy during temporary oral anticoagulation interruption for elective surgical or invasive procedures. Studies were excluded if the reporting of thromboembolic or bleeding outcomes was unclear, or if they focused exclusively on patients with renal failure (ASH 2011; abstract 545). All studies were reviewed by two independent investigators.

The researchers identified and screened 1,164 studies for review. Of these, 35 studies that included 7,169 bridged patients were selected for the final review. Most of the studies (33) were observational, and only two were randomized. The median follow-up was 30 days.

The most common indication for anticoagulation was atrial fibrillation (44%), followed by mechanical valve (24%), prior venous thromboembolism (22%), and other (10%).

The most common preoperative strategy was to discontinue oral anticoagulation more than 3 days in advance. Low-molecular-weight heparin was most commonly used, both preoperatively and postoperatively.

Dr. Yudin reported that thromboembolic events, which were primarily arterial in nature, occurred in 73 of the 7,169 patients (mean rate, 0.96%). The mean rate of overall bleeding was 13.01%, whereas the mean rate of major bleeding was 4.32%.

Eight of the studies included in the final analysis had control groups from which the researchers were able to pull data to determine an odds ratio for thromboembolism with bridging vs. no bridging. These studies included 1,691 bridged patients and 3,493 nonbridged patients. The odds ratio for thromboembolic events was 0.80, with a 95% confidence interval (CI) of 0.42-1.54, "suggesting no risk reduction for thromboembolic events with heparin or low-molecular-weight bridging," Dr. Yudin said. "There was also no difference between these two groups in the risk for arterial or venous thromboembolism."

To determine the risk of overall bleeding, the researchers pulled data from 13 studies that included control groups. These studies included 1,935 bridged patients and 5,160 nonbridged patients. The odds ratio for overall bleeding with bridging was 5.40 (95% CI, 3.00-9.74). "This suggested an increased risk of overall bleeding with bridging anticoagulation, but there was significant heterogeneity noted across these studies."

For major bleeding, five studies with control groups were assessed. These included 1,397 bridged patients and 2,104 nonbridged patients. The odds ratio for major bleeding was 3.60 (95% CI, 1.52-8.50), "again suggesting an increased risk in major bleeding with bridging," she said. "There was significant heterogeneity noted across studies."

Dr. Yudin acknowledged that the review had certain limitations: Most of the studies included in the analysis were observational, and only about a third had control groups. "Our control groups consisted largely of low-thromboembolic-risk patients, or patients who were not chronically on vitamin K antagonists, suggesting that they had a different risk profile for thromboembolism than many of the bridged patients," she said.

The findings "underline the need for studies of higher [methodological] quality in periprocedural bridging," she concluded. "It also tells us that there is a need for standardized definitions in terms of outcomes. We suspect that much of our heterogeneity had to do with varying definitions for outcomes such as major bleeding."

Dr. Yudin said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who receive heparin bridging during an interruption of oral anticoagulation appear to be at a 5.4-fold increased risk of overall bleeding and a 3.6-fold increased risk of major bleeding, without a reduction in risk of thromboembolic events.

Those are key findings from a systematic review and meta-analysis of recently published medical literature presented by Dr. Jovana Yudin at the annual meeting of the American Society of Hematology.

Antithrombotic and thrombolytic therapy guidelines published by the American College of Chest Physicians in 2008 recommended bridging according to an individualized approach (Chest 2008;133[suppl. 6]:299S-339S).

"They suggested bridging according to patients’ bleeding and thromboembolic risk," said Dr. Yudin, a fellow in the hematology residency program at McMaster University, Hamilton, Ont. "Within the last decade, several new studies have been published using periprocedural bridging. In these studies, low-molecular-weight heparin has been used with increased frequency. However, optimal strategies for bridging remain unclear. Our objective was to do a systematic review and meta-analysis of bridging trials published in the last decade to look at thromboembolic risk as well as bleeding risk."

Dr. Yudin and her associates searched the MEDLINE, EMBASE, and Cochrane Collaboration databases for systematic reviews and meta-analyses of studies published between Jan. 1, 2001, and July 31, 2010, that examined bleeding and thromboembolic events in patients receiving bridging therapy during temporary oral anticoagulation interruption for elective surgical or invasive procedures. Studies were excluded if the reporting of thromboembolic or bleeding outcomes was unclear, or if they focused exclusively on patients with renal failure (ASH 2011; abstract 545). All studies were reviewed by two independent investigators.

The researchers identified and screened 1,164 studies for review. Of these, 35 studies that included 7,169 bridged patients were selected for the final review. Most of the studies (33) were observational, and only two were randomized. The median follow-up was 30 days.

The most common indication for anticoagulation was atrial fibrillation (44%), followed by mechanical valve (24%), prior venous thromboembolism (22%), and other (10%).

The most common preoperative strategy was to discontinue oral anticoagulation more than 3 days in advance. Low-molecular-weight heparin was most commonly used, both preoperatively and postoperatively.

Dr. Yudin reported that thromboembolic events, which were primarily arterial in nature, occurred in 73 of the 7,169 patients (mean rate, 0.96%). The mean rate of overall bleeding was 13.01%, whereas the mean rate of major bleeding was 4.32%.

Eight of the studies included in the final analysis had control groups from which the researchers were able to pull data to determine an odds ratio for thromboembolism with bridging vs. no bridging. These studies included 1,691 bridged patients and 3,493 nonbridged patients. The odds ratio for thromboembolic events was 0.80, with a 95% confidence interval (CI) of 0.42-1.54, "suggesting no risk reduction for thromboembolic events with heparin or low-molecular-weight bridging," Dr. Yudin said. "There was also no difference between these two groups in the risk for arterial or venous thromboembolism."

To determine the risk of overall bleeding, the researchers pulled data from 13 studies that included control groups. These studies included 1,935 bridged patients and 5,160 nonbridged patients. The odds ratio for overall bleeding with bridging was 5.40 (95% CI, 3.00-9.74). "This suggested an increased risk of overall bleeding with bridging anticoagulation, but there was significant heterogeneity noted across these studies."

For major bleeding, five studies with control groups were assessed. These included 1,397 bridged patients and 2,104 nonbridged patients. The odds ratio for major bleeding was 3.60 (95% CI, 1.52-8.50), "again suggesting an increased risk in major bleeding with bridging," she said. "There was significant heterogeneity noted across studies."

Dr. Yudin acknowledged that the review had certain limitations: Most of the studies included in the analysis were observational, and only about a third had control groups. "Our control groups consisted largely of low-thromboembolic-risk patients, or patients who were not chronically on vitamin K antagonists, suggesting that they had a different risk profile for thromboembolism than many of the bridged patients," she said.

The findings "underline the need for studies of higher [methodological] quality in periprocedural bridging," she concluded. "It also tells us that there is a need for standardized definitions in terms of outcomes. We suspect that much of our heterogeneity had to do with varying definitions for outcomes such as major bleeding."

Dr. Yudin said that she had no relevant financial conflicts to disclose.

SAN DIEGO – Obtaining a baseline D-dimer level can identify acutely ill patients at high risk of venous thromboembolism, results from a large analysis have shown.

In fact, the rate of venous thromboembolism (VTE) was 3.5- to 4-fold higher for patients with a baseline D-dimer level more than twice the upper limit of normal, compared with patients whose D-dimer was twice the upper limit of normal or less, Dr. Alexander T. Cohen reported at the annual meeting of the American Society of Hematology.

The findings come from a subset analysis of patients in MAGELLAN, a trial of 8,101 acutely ill, hospitalized adults who were randomized to either oral rivaroxaban (Xarelto) prophylaxis 10 mg once daily for 35 days or to standard enoxaparin (Lovenox) 40 mg once daily for 10 days, followed by placebo. The patients were assessed with ultrasonography on day 10 and day 35. In the overall study population, rivaroxaban met both of its primary outcomes: noninferiority at day 10 vs. enoxaparin and superiority at day 35 vs. enoxaparin, followed by placebo. Rates of clinically relevant bleeding were low in general but were higher for rivaroxaban than for enoxaparin with placebo. MAGELLAN’s primary findings were presented at the 2011 annual meeting of the American College of Cardiology but have not yet been published.

For the current study, outcomes in MAGELLAN were analyzed to investigate the relationship between D-dimer levels and VTE risk, and the effect of rivaroxaban on this risk. Dr. Cohen of the department of surgery at King’s College Hospital, London, and his associates divided patients into two groups: those with D-dimer levels less than or equal to two times the upper limit of normal or less (group 1) and those with D-dimer levels greater than two times the upper limit of normal (group 2).

The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic nonfatal pulmonary embolism, and VTE-related death. The principal safety outcomes were major and nonmajor clinically relevant bleeding recorded within 2 days after the last intake of study medication. Both outcomes were assessed on day 10 and day 35, and the prespecified net clinical benefit was defined as a composite of the primary efficacy and principal safety outcomes.

The mean age of the patients was 67 years in group 1 and 71 years in group 2. The baseline median D-dimer level was 0.94 mg/L in all patients. Baseline D-dimer level was higher in patients who experienced a primary efficacy outcome event, compared with those who did not have such an event (a median of 1.98 mg/L vs. 0.92 mg/L). Patients in group 2 were about four times as likely to have a VTE by day 10, compared with those in group 1. At day 10, rivaroxaban was noninferior for the primary efficacy outcome, compared with enoxaparin, among patients in group 2.

At day 35, patients in group 2 who were assigned to the rivaroxaban arm had a reduction in their relative risk of the primary efficacy outcome by 29%, compared with those who were assigned to the enoxaparin-placebo arm, a significant difference that translated into an absolute risk reduction of 2.8% (P = .01). No such differences were observed in group 1.

Patients who had a high D-dimer level at baseline were at increased risk of an event occurring between day 11 and day 35, and rivaroxaban reduced that risk, compared with placebo, during this time period, Dr. Cohen said. "Perhaps assessment of D-dimer after 10 days of standard prophylaxis may indicate which patients benefit from rivaroxaban prophylaxis," he noted.

In both D-dimer groups, the rate of clinically relevant bleeding was significantly higher among patients treated with rivaroxaban, compared with those treated with enoxaparin, followed by placebo, across the entire study period. In the net clinical benefit outcomes analysis, the hazard ratio at day 10 was 1.63 for group 1 and 0.96 for group 2, while the hazard ratio at day 35 was 1.71 for group 1 and 1.03 for group 2.

MAGELLAN was funded by Bayer (which licenses rivaroxaban) and Johnson & Johnson (parent company of Janssen Pharmaceuticals, which manufactures rivaroxaban). Dr. Cohen disclosed that he has served as a medical consultant for, and has received honoraria and clinical trial funding from, numerous pharmaceutical companies, including Bayer, Johnson & Johnson, and Sanofi-Aventis.

SAN DIEGO – Obtaining a baseline D-dimer level can identify acutely ill patients at high risk of venous thromboembolism, results from a large analysis have shown.

In fact, the rate of venous thromboembolism (VTE) was 3.5- to 4-fold higher for patients with a baseline D-dimer level more than twice the upper limit of normal, compared with patients whose D-dimer was twice the upper limit of normal or less, Dr. Alexander T. Cohen reported at the annual meeting of the American Society of Hematology.

The findings come from a subset analysis of patients in MAGELLAN, a trial of 8,101 acutely ill, hospitalized adults who were randomized to either oral rivaroxaban (Xarelto) prophylaxis 10 mg once daily for 35 days or to standard enoxaparin (Lovenox) 40 mg once daily for 10 days, followed by placebo. The patients were assessed with ultrasonography on day 10 and day 35. In the overall study population, rivaroxaban met both of its primary outcomes: noninferiority at day 10 vs. enoxaparin and superiority at day 35 vs. enoxaparin, followed by placebo. Rates of clinically relevant bleeding were low in general but were higher for rivaroxaban than for enoxaparin with placebo. MAGELLAN’s primary findings were presented at the 2011 annual meeting of the American College of Cardiology but have not yet been published.

For the current study, outcomes in MAGELLAN were analyzed to investigate the relationship between D-dimer levels and VTE risk, and the effect of rivaroxaban on this risk. Dr. Cohen of the department of surgery at King’s College Hospital, London, and his associates divided patients into two groups: those with D-dimer levels less than or equal to two times the upper limit of normal or less (group 1) and those with D-dimer levels greater than two times the upper limit of normal (group 2).

The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic nonfatal pulmonary embolism, and VTE-related death. The principal safety outcomes were major and nonmajor clinically relevant bleeding recorded within 2 days after the last intake of study medication. Both outcomes were assessed on day 10 and day 35, and the prespecified net clinical benefit was defined as a composite of the primary efficacy and principal safety outcomes.

The mean age of the patients was 67 years in group 1 and 71 years in group 2. The baseline median D-dimer level was 0.94 mg/L in all patients. Baseline D-dimer level was higher in patients who experienced a primary efficacy outcome event, compared with those who did not have such an event (a median of 1.98 mg/L vs. 0.92 mg/L). Patients in group 2 were about four times as likely to have a VTE by day 10, compared with those in group 1. At day 10, rivaroxaban was noninferior for the primary efficacy outcome, compared with enoxaparin, among patients in group 2.

At day 35, patients in group 2 who were assigned to the rivaroxaban arm had a reduction in their relative risk of the primary efficacy outcome by 29%, compared with those who were assigned to the enoxaparin-placebo arm, a significant difference that translated into an absolute risk reduction of 2.8% (P = .01). No such differences were observed in group 1.

Patients who had a high D-dimer level at baseline were at increased risk of an event occurring between day 11 and day 35, and rivaroxaban reduced that risk, compared with placebo, during this time period, Dr. Cohen said. "Perhaps assessment of D-dimer after 10 days of standard prophylaxis may indicate which patients benefit from rivaroxaban prophylaxis," he noted.

In both D-dimer groups, the rate of clinically relevant bleeding was significantly higher among patients treated with rivaroxaban, compared with those treated with enoxaparin, followed by placebo, across the entire study period. In the net clinical benefit outcomes analysis, the hazard ratio at day 10 was 1.63 for group 1 and 0.96 for group 2, while the hazard ratio at day 35 was 1.71 for group 1 and 1.03 for group 2.

MAGELLAN was funded by Bayer (which licenses rivaroxaban) and Johnson & Johnson (parent company of Janssen Pharmaceuticals, which manufactures rivaroxaban). Dr. Cohen disclosed that he has served as a medical consultant for, and has received honoraria and clinical trial funding from, numerous pharmaceutical companies, including Bayer, Johnson & Johnson, and Sanofi-Aventis.

SAN DIEGO – Obtaining a baseline D-dimer level can identify acutely ill patients at high risk of venous thromboembolism, results from a large analysis have shown.

In fact, the rate of venous thromboembolism (VTE) was 3.5- to 4-fold higher for patients with a baseline D-dimer level more than twice the upper limit of normal, compared with patients whose D-dimer was twice the upper limit of normal or less, Dr. Alexander T. Cohen reported at the annual meeting of the American Society of Hematology.

The findings come from a subset analysis of patients in MAGELLAN, a trial of 8,101 acutely ill, hospitalized adults who were randomized to either oral rivaroxaban (Xarelto) prophylaxis 10 mg once daily for 35 days or to standard enoxaparin (Lovenox) 40 mg once daily for 10 days, followed by placebo. The patients were assessed with ultrasonography on day 10 and day 35. In the overall study population, rivaroxaban met both of its primary outcomes: noninferiority at day 10 vs. enoxaparin and superiority at day 35 vs. enoxaparin, followed by placebo. Rates of clinically relevant bleeding were low in general but were higher for rivaroxaban than for enoxaparin with placebo. MAGELLAN’s primary findings were presented at the 2011 annual meeting of the American College of Cardiology but have not yet been published.

For the current study, outcomes in MAGELLAN were analyzed to investigate the relationship between D-dimer levels and VTE risk, and the effect of rivaroxaban on this risk. Dr. Cohen of the department of surgery at King’s College Hospital, London, and his associates divided patients into two groups: those with D-dimer levels less than or equal to two times the upper limit of normal or less (group 1) and those with D-dimer levels greater than two times the upper limit of normal (group 2).

The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic nonfatal pulmonary embolism, and VTE-related death. The principal safety outcomes were major and nonmajor clinically relevant bleeding recorded within 2 days after the last intake of study medication. Both outcomes were assessed on day 10 and day 35, and the prespecified net clinical benefit was defined as a composite of the primary efficacy and principal safety outcomes.

The mean age of the patients was 67 years in group 1 and 71 years in group 2. The baseline median D-dimer level was 0.94 mg/L in all patients. Baseline D-dimer level was higher in patients who experienced a primary efficacy outcome event, compared with those who did not have such an event (a median of 1.98 mg/L vs. 0.92 mg/L). Patients in group 2 were about four times as likely to have a VTE by day 10, compared with those in group 1. At day 10, rivaroxaban was noninferior for the primary efficacy outcome, compared with enoxaparin, among patients in group 2.

At day 35, patients in group 2 who were assigned to the rivaroxaban arm had a reduction in their relative risk of the primary efficacy outcome by 29%, compared with those who were assigned to the enoxaparin-placebo arm, a significant difference that translated into an absolute risk reduction of 2.8% (P = .01). No such differences were observed in group 1.

Patients who had a high D-dimer level at baseline were at increased risk of an event occurring between day 11 and day 35, and rivaroxaban reduced that risk, compared with placebo, during this time period, Dr. Cohen said. "Perhaps assessment of D-dimer after 10 days of standard prophylaxis may indicate which patients benefit from rivaroxaban prophylaxis," he noted.

In both D-dimer groups, the rate of clinically relevant bleeding was significantly higher among patients treated with rivaroxaban, compared with those treated with enoxaparin, followed by placebo, across the entire study period. In the net clinical benefit outcomes analysis, the hazard ratio at day 10 was 1.63 for group 1 and 0.96 for group 2, while the hazard ratio at day 35 was 1.71 for group 1 and 1.03 for group 2.

MAGELLAN was funded by Bayer (which licenses rivaroxaban) and Johnson & Johnson (parent company of Janssen Pharmaceuticals, which manufactures rivaroxaban). Dr. Cohen disclosed that he has served as a medical consultant for, and has received honoraria and clinical trial funding from, numerous pharmaceutical companies, including Bayer, Johnson & Johnson, and Sanofi-Aventis.

SAN DIEGO – Patients who had severe sickle cell disease and underwent surgery without a preoperative blood transfusion had more than twice as many perioperative complications and 10 times as many severe adverse events as similar patients who received transfusions.

Those are key findings from the TAPS (Transfusion Alternatives Preoperatively in Sickle Cell Disease) trial, a randomized study that was carried out between November 2007 and March 2011 at 22 sites in the United Kingdom, the Netherlands, and Canada.

The findings "show that patients with severe sickle cell disease should be given a blood transfusion before surgery," Dr. Jo Howard said during a press briefing at the annual meeting of the American Society of Hematology. "In addition, it suggests that we should consider giving a blood transfusion to patients with other types of sickle cell disease."

The purpose of TAPS was to assess the clinical benefit of preoperative transfusion to alleviate perioperative complications in patients with sickle cell disease who had sickle cell anemia (HbSS) and sickle-beta⁰-thalassemia (HbSbeta⁰) and who were undergoing low- or medium-risk procedures such as abdominal surgery or tonsillectomy.

"Prior to the trial, it was clear that patients with sickle cell disease having surgery were more likely to have complications, but it wasn’t clear whether transfusion decreased these or not, and in which situations [transfusion] should be used," said Dr. Howard, a consultant hematologist at Guy’s and St. Thomas’ Hospitals, London. "In the United Kingdom in 2005, there was a wide variation in practice, and in fact a decrease in use of blood transfusions in part because of concern about the risks of transfusions."

The primary outcome of the trial was the number of patients with severe sickle cell disease who had significant complications from randomization to 30 days post surgery. The researchers also tracked the amount of blood received, the number of days spent in the hospital, and the readmission rates.

Of 343 patients initially screened for the trial, 70 were randomized into one of two groups. The 35 patients in group 1 did not receive a blood transfusion. The 35 in group 2 received a top-up transfusion if their hemoglobin levels were less than 9g/dL, or a partial exchange if their hemoglobin levels were 9g/dL or higher. The trial was closed in March of 2011 because a higher proportion of serious adverse events occurred in group 1, compared with group 2.

The final analysis included 33 patients in group 1 and 34 patients in group 2. Dr. Howard reported that 39% of patients in group 1 experienced a perioperative complication, compared with 15% of patients in group 2.

In addition, 30% of patients in group 1 and 3% in group 2 experienced a serious adverse event, primarily acute chest syndrome (seen in 27% of patients in group 1 and in 3% of patients in group 2).

Dr. Howard acknowledged certain limitations of TAPS, including its early closure and the relatively small number of patients enrolled in the trial.

The TAPS trial was sponsored and funded by National Health Service Blood and Transplant in the United Kingdom.

SAN DIEGO – Patients who had severe sickle cell disease and underwent surgery without a preoperative blood transfusion had more than twice as many perioperative complications and 10 times as many severe adverse events as similar patients who received transfusions.

Those are key findings from the TAPS (Transfusion Alternatives Preoperatively in Sickle Cell Disease) trial, a randomized study that was carried out between November 2007 and March 2011 at 22 sites in the United Kingdom, the Netherlands, and Canada.

The findings "show that patients with severe sickle cell disease should be given a blood transfusion before surgery," Dr. Jo Howard said during a press briefing at the annual meeting of the American Society of Hematology. "In addition, it suggests that we should consider giving a blood transfusion to patients with other types of sickle cell disease."

The purpose of TAPS was to assess the clinical benefit of preoperative transfusion to alleviate perioperative complications in patients with sickle cell disease who had sickle cell anemia (HbSS) and sickle-beta⁰-thalassemia (HbSbeta⁰) and who were undergoing low- or medium-risk procedures such as abdominal surgery or tonsillectomy.

"Prior to the trial, it was clear that patients with sickle cell disease having surgery were more likely to have complications, but it wasn’t clear whether transfusion decreased these or not, and in which situations [transfusion] should be used," said Dr. Howard, a consultant hematologist at Guy’s and St. Thomas’ Hospitals, London. "In the United Kingdom in 2005, there was a wide variation in practice, and in fact a decrease in use of blood transfusions in part because of concern about the risks of transfusions."

The primary outcome of the trial was the number of patients with severe sickle cell disease who had significant complications from randomization to 30 days post surgery. The researchers also tracked the amount of blood received, the number of days spent in the hospital, and the readmission rates.

Of 343 patients initially screened for the trial, 70 were randomized into one of two groups. The 35 patients in group 1 did not receive a blood transfusion. The 35 in group 2 received a top-up transfusion if their hemoglobin levels were less than 9g/dL, or a partial exchange if their hemoglobin levels were 9g/dL or higher. The trial was closed in March of 2011 because a higher proportion of serious adverse events occurred in group 1, compared with group 2.

The final analysis included 33 patients in group 1 and 34 patients in group 2. Dr. Howard reported that 39% of patients in group 1 experienced a perioperative complication, compared with 15% of patients in group 2.

In addition, 30% of patients in group 1 and 3% in group 2 experienced a serious adverse event, primarily acute chest syndrome (seen in 27% of patients in group 1 and in 3% of patients in group 2).

Dr. Howard acknowledged certain limitations of TAPS, including its early closure and the relatively small number of patients enrolled in the trial.

The TAPS trial was sponsored and funded by National Health Service Blood and Transplant in the United Kingdom.

SAN DIEGO – Patients who had severe sickle cell disease and underwent surgery without a preoperative blood transfusion had more than twice as many perioperative complications and 10 times as many severe adverse events as similar patients who received transfusions.

Those are key findings from the TAPS (Transfusion Alternatives Preoperatively in Sickle Cell Disease) trial, a randomized study that was carried out between November 2007 and March 2011 at 22 sites in the United Kingdom, the Netherlands, and Canada.

The findings "show that patients with severe sickle cell disease should be given a blood transfusion before surgery," Dr. Jo Howard said during a press briefing at the annual meeting of the American Society of Hematology. "In addition, it suggests that we should consider giving a blood transfusion to patients with other types of sickle cell disease."

The purpose of TAPS was to assess the clinical benefit of preoperative transfusion to alleviate perioperative complications in patients with sickle cell disease who had sickle cell anemia (HbSS) and sickle-beta⁰-thalassemia (HbSbeta⁰) and who were undergoing low- or medium-risk procedures such as abdominal surgery or tonsillectomy.

"Prior to the trial, it was clear that patients with sickle cell disease having surgery were more likely to have complications, but it wasn’t clear whether transfusion decreased these or not, and in which situations [transfusion] should be used," said Dr. Howard, a consultant hematologist at Guy’s and St. Thomas’ Hospitals, London. "In the United Kingdom in 2005, there was a wide variation in practice, and in fact a decrease in use of blood transfusions in part because of concern about the risks of transfusions."

The primary outcome of the trial was the number of patients with severe sickle cell disease who had significant complications from randomization to 30 days post surgery. The researchers also tracked the amount of blood received, the number of days spent in the hospital, and the readmission rates.

Of 343 patients initially screened for the trial, 70 were randomized into one of two groups. The 35 patients in group 1 did not receive a blood transfusion. The 35 in group 2 received a top-up transfusion if their hemoglobin levels were less than 9g/dL, or a partial exchange if their hemoglobin levels were 9g/dL or higher. The trial was closed in March of 2011 because a higher proportion of serious adverse events occurred in group 1, compared with group 2.

The final analysis included 33 patients in group 1 and 34 patients in group 2. Dr. Howard reported that 39% of patients in group 1 experienced a perioperative complication, compared with 15% of patients in group 2.

In addition, 30% of patients in group 1 and 3% in group 2 experienced a serious adverse event, primarily acute chest syndrome (seen in 27% of patients in group 1 and in 3% of patients in group 2).

Dr. Howard acknowledged certain limitations of TAPS, including its early closure and the relatively small number of patients enrolled in the trial.

The TAPS trial was sponsored and funded by National Health Service Blood and Transplant in the United Kingdom.

SAN DIEGO – The standard approach of waiting to treat smoldering multiple myeloma until it progresses to active disease is being called into question by robust results from a phase III trial of early treatment with lenalidomide and dexamethasone.

Among 119 patients with smoldering myeloma who were at high risk of disease progression, 59% of those randomized to no treatment converted to symptomatic myeloma, compared with 15% of those given lenalidomide (Revlimid) and dexamethasone as induction therapy, followed by lenalidomide maintenance.

The estimated hazard ratio was 6.0, corresponding to a median time to progression of 23 months in the abstention arm vs. median not reached in the active treatment arm (P less than .0001). Median follow-up was 32 months (range, 12-49 months).

Early treatment also produced a benefit in overall survival, with an acceptable toxicity profile and no safety warnings at the present time, Dr. María-Victoria Mateos said at the annual meeting of the American Society of Hematology (ASH).

She pointed out that conventional agents have shown no benefit in overall response rate, time to progression, or overall survival, whereas novel agents such as thalidomide increased partial responses by 30% or more, but at a cost of higher toxicity and shorter time to treatment in those patients achieving a partial response.

At last year’s ASH meeting, the Spanish Myeloma Group presented results from the trial showing lower conversion rates in the abstention arm, but the longer follow-up has strengthened the findings and the case for early treatment, said session comoderator Dr. Meral Beksac, professor of hematology at Ankara (Turkey) University.

"This is the first [study] with such big success," she said in an interview. "What is a matter of debate is how to select those patients with high-risk smoldering myeloma, and I think their definition is a good one. It’s not based on gene expression; it’s a widely applicable definition."

Several risk factors predicting high-risk symptomatic disease have been used, including more than 10% of plasma cells (PCs) in bone marrow; serum monoclonal component (MC) greater than 30 g/L; more than 95% aberrant PCs by immunophenotyping; or abnormal MRI studies, explained Dr. Mateos of the University Hospital of Salamanca (Spain).

In this trial, the high-risk population was defined by the presence of more than 10% of PCs in bone marrow and MC greater than 30 g/L, or – if only one criterion was present – patients had to have 95% of aberrant PCs within the total PCs bone marrow compartment by immunophenotyping plus immunoparesis.

Patients in the active treatment arm received nine 4-week cycles of lenalidomide (25 mg daily) on days 1-21 plus dexamethasone (20 mg daily) on days 1-4 and 12-15, followed by maintenance until disease progression with lenalidomide (10 mg) on days 1-21 every 2 months. The trial was amended in May 2010, however, to monthly lenalidomide maintenance, and was further amended in August 2011 to stop treatment at 2 years.

Of the nine patients who progressed on active treatment, five progressed after early discontinuation from the trial, Dr. Mateos said. In all, 14 patients developed biological progression during maintenance, and low-dose dexamethasone was added according to the protocol. Of these patients, 2 had a partial response and 10 experienced stable disease, of which 8 remain stable after a median follow-up of 19 months.

At 5 years, 94% of patients who were treated with lenalidomide plus dexamethasone were alive, compared with 79% who were given no treatment (HR, 5.01; P = .03,), she said.

Dr. Beksac said that cost might be an issue in translating the results to daily practice, particularly with the monthly lenalidomide maintenance schedule. She also suggested that in light of new data presented at the meeting (on affirmation of a second-cancer signal after lenalidomide in new multiple myeloma patients, and on evidence that lenalidomide maintenance holds back myeloma in the elderly), some physicians may want to wait until more is known about the risk of second primary malignancies (SPMs) with lenalidomide therapy.

"Maybe we can wait at least 2 more years to see the SPMs and to be on the safer side, and then it could be a clinical practice," she said.

SPMs were detected in three patients, representing 5% of the 57 patients treated with lenalidomide and dexamethasone. Of the two prostate cancer cases, both men had prostate hyperplasia prior to treatment, according to their medical records, whereas the patient diagnosed with polycythemia vera had a JAK2 gene mutation, the major cause of PV, at study entry, Dr. Mateos pointed out.

Dr. Mateos reported receiving honoraria from Celgene, Millennium Pharmaceuticals, and Janssen. A coauthor reported receiving honoraria from Celgene and Janssen, and four coauthors reported employment with Celgene, the maker of lenalidomide. Dr. Beksac reported receiving honoraria from and serving as a speaker for Celgene and Janssen-Cilag.

SAN DIEGO – The standard approach of waiting to treat smoldering multiple myeloma until it progresses to active disease is being called into question by robust results from a phase III trial of early treatment with lenalidomide and dexamethasone.

Among 119 patients with smoldering myeloma who were at high risk of disease progression, 59% of those randomized to no treatment converted to symptomatic myeloma, compared with 15% of those given lenalidomide (Revlimid) and dexamethasone as induction therapy, followed by lenalidomide maintenance.

The estimated hazard ratio was 6.0, corresponding to a median time to progression of 23 months in the abstention arm vs. median not reached in the active treatment arm (P less than .0001). Median follow-up was 32 months (range, 12-49 months).

Early treatment also produced a benefit in overall survival, with an acceptable toxicity profile and no safety warnings at the present time, Dr. María-Victoria Mateos said at the annual meeting of the American Society of Hematology (ASH).

She pointed out that conventional agents have shown no benefit in overall response rate, time to progression, or overall survival, whereas novel agents such as thalidomide increased partial responses by 30% or more, but at a cost of higher toxicity and shorter time to treatment in those patients achieving a partial response.

At last year’s ASH meeting, the Spanish Myeloma Group presented results from the trial showing lower conversion rates in the abstention arm, but the longer follow-up has strengthened the findings and the case for early treatment, said session comoderator Dr. Meral Beksac, professor of hematology at Ankara (Turkey) University.

"This is the first [study] with such big success," she said in an interview. "What is a matter of debate is how to select those patients with high-risk smoldering myeloma, and I think their definition is a good one. It’s not based on gene expression; it’s a widely applicable definition."

Several risk factors predicting high-risk symptomatic disease have been used, including more than 10% of plasma cells (PCs) in bone marrow; serum monoclonal component (MC) greater than 30 g/L; more than 95% aberrant PCs by immunophenotyping; or abnormal MRI studies, explained Dr. Mateos of the University Hospital of Salamanca (Spain).

In this trial, the high-risk population was defined by the presence of more than 10% of PCs in bone marrow and MC greater than 30 g/L, or – if only one criterion was present – patients had to have 95% of aberrant PCs within the total PCs bone marrow compartment by immunophenotyping plus immunoparesis.

Patients in the active treatment arm received nine 4-week cycles of lenalidomide (25 mg daily) on days 1-21 plus dexamethasone (20 mg daily) on days 1-4 and 12-15, followed by maintenance until disease progression with lenalidomide (10 mg) on days 1-21 every 2 months. The trial was amended in May 2010, however, to monthly lenalidomide maintenance, and was further amended in August 2011 to stop treatment at 2 years.

Of the nine patients who progressed on active treatment, five progressed after early discontinuation from the trial, Dr. Mateos said. In all, 14 patients developed biological progression during maintenance, and low-dose dexamethasone was added according to the protocol. Of these patients, 2 had a partial response and 10 experienced stable disease, of which 8 remain stable after a median follow-up of 19 months.

At 5 years, 94% of patients who were treated with lenalidomide plus dexamethasone were alive, compared with 79% who were given no treatment (HR, 5.01; P = .03,), she said.

Dr. Beksac said that cost might be an issue in translating the results to daily practice, particularly with the monthly lenalidomide maintenance schedule. She also suggested that in light of new data presented at the meeting (on affirmation of a second-cancer signal after lenalidomide in new multiple myeloma patients, and on evidence that lenalidomide maintenance holds back myeloma in the elderly), some physicians may want to wait until more is known about the risk of second primary malignancies (SPMs) with lenalidomide therapy.

"Maybe we can wait at least 2 more years to see the SPMs and to be on the safer side, and then it could be a clinical practice," she said.

SPMs were detected in three patients, representing 5% of the 57 patients treated with lenalidomide and dexamethasone. Of the two prostate cancer cases, both men had prostate hyperplasia prior to treatment, according to their medical records, whereas the patient diagnosed with polycythemia vera had a JAK2 gene mutation, the major cause of PV, at study entry, Dr. Mateos pointed out.

Dr. Mateos reported receiving honoraria from Celgene, Millennium Pharmaceuticals, and Janssen. A coauthor reported receiving honoraria from Celgene and Janssen, and four coauthors reported employment with Celgene, the maker of lenalidomide. Dr. Beksac reported receiving honoraria from and serving as a speaker for Celgene and Janssen-Cilag.

SAN DIEGO – The standard approach of waiting to treat smoldering multiple myeloma until it progresses to active disease is being called into question by robust results from a phase III trial of early treatment with lenalidomide and dexamethasone.

Among 119 patients with smoldering myeloma who were at high risk of disease progression, 59% of those randomized to no treatment converted to symptomatic myeloma, compared with 15% of those given lenalidomide (Revlimid) and dexamethasone as induction therapy, followed by lenalidomide maintenance.

The estimated hazard ratio was 6.0, corresponding to a median time to progression of 23 months in the abstention arm vs. median not reached in the active treatment arm (P less than .0001). Median follow-up was 32 months (range, 12-49 months).

Early treatment also produced a benefit in overall survival, with an acceptable toxicity profile and no safety warnings at the present time, Dr. María-Victoria Mateos said at the annual meeting of the American Society of Hematology (ASH).

She pointed out that conventional agents have shown no benefit in overall response rate, time to progression, or overall survival, whereas novel agents such as thalidomide increased partial responses by 30% or more, but at a cost of higher toxicity and shorter time to treatment in those patients achieving a partial response.

At last year’s ASH meeting, the Spanish Myeloma Group presented results from the trial showing lower conversion rates in the abstention arm, but the longer follow-up has strengthened the findings and the case for early treatment, said session comoderator Dr. Meral Beksac, professor of hematology at Ankara (Turkey) University.

"This is the first [study] with such big success," she said in an interview. "What is a matter of debate is how to select those patients with high-risk smoldering myeloma, and I think their definition is a good one. It’s not based on gene expression; it’s a widely applicable definition."

Several risk factors predicting high-risk symptomatic disease have been used, including more than 10% of plasma cells (PCs) in bone marrow; serum monoclonal component (MC) greater than 30 g/L; more than 95% aberrant PCs by immunophenotyping; or abnormal MRI studies, explained Dr. Mateos of the University Hospital of Salamanca (Spain).

In this trial, the high-risk population was defined by the presence of more than 10% of PCs in bone marrow and MC greater than 30 g/L, or – if only one criterion was present – patients had to have 95% of aberrant PCs within the total PCs bone marrow compartment by immunophenotyping plus immunoparesis.

Patients in the active treatment arm received nine 4-week cycles of lenalidomide (25 mg daily) on days 1-21 plus dexamethasone (20 mg daily) on days 1-4 and 12-15, followed by maintenance until disease progression with lenalidomide (10 mg) on days 1-21 every 2 months. The trial was amended in May 2010, however, to monthly lenalidomide maintenance, and was further amended in August 2011 to stop treatment at 2 years.

Of the nine patients who progressed on active treatment, five progressed after early discontinuation from the trial, Dr. Mateos said. In all, 14 patients developed biological progression during maintenance, and low-dose dexamethasone was added according to the protocol. Of these patients, 2 had a partial response and 10 experienced stable disease, of which 8 remain stable after a median follow-up of 19 months.

At 5 years, 94% of patients who were treated with lenalidomide plus dexamethasone were alive, compared with 79% who were given no treatment (HR, 5.01; P = .03,), she said.

Dr. Beksac said that cost might be an issue in translating the results to daily practice, particularly with the monthly lenalidomide maintenance schedule. She also suggested that in light of new data presented at the meeting (on affirmation of a second-cancer signal after lenalidomide in new multiple myeloma patients, and on evidence that lenalidomide maintenance holds back myeloma in the elderly), some physicians may want to wait until more is known about the risk of second primary malignancies (SPMs) with lenalidomide therapy.

"Maybe we can wait at least 2 more years to see the SPMs and to be on the safer side, and then it could be a clinical practice," she said.

SPMs were detected in three patients, representing 5% of the 57 patients treated with lenalidomide and dexamethasone. Of the two prostate cancer cases, both men had prostate hyperplasia prior to treatment, according to their medical records, whereas the patient diagnosed with polycythemia vera had a JAK2 gene mutation, the major cause of PV, at study entry, Dr. Mateos pointed out.

Dr. Mateos reported receiving honoraria from Celgene, Millennium Pharmaceuticals, and Janssen. A coauthor reported receiving honoraria from Celgene and Janssen, and four coauthors reported employment with Celgene, the maker of lenalidomide. Dr. Beksac reported receiving honoraria from and serving as a speaker for Celgene and Janssen-Cilag.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.