2015 ISTH Congress

Micrograph showing TTP

Image by Erhabor Osaro

TORONTO—Adding the anti-von Willebrand factor nanobody caplacizumab to standard therapy can provide clinical benefits for patients with

acquired thrombotic thrombocytopenic purpura (TTP), according to research presented at the 2015 ISTH Congress.

In the phase 2 TITAN trial, patients who received caplacizumab and standard therapy had a significantly shorter time to platelet normalization than patients who received standard therapy and placebo.

Caplacizumab was also associated with a shorter time to troponin, creatinine, and lactate dehydrogenase (LDH) normalization, as well as a reduced need for plasma exchange (PE).

However, some patients relapsed after stopping caplacizumab, and the majority of these relapses could be linked to unresolved disease activity. The drug also increased the risk of mild-to-moderate bleeding compared to placebo.

Flora Peyvandi, MD, PhD, of the University of Milan in Italy, presented data from the TITAN trial at ISTH as abstract LB006. Information on using ADAMTS13 activity for treatment monitoring in the TITAN trial was also presented at the meeting, as abstract OR363.

TITAN was sponsored by Ablynx, the company developing caplacizumab.

The study enrolled 75 patients with acquired TTP from January 2011 to January 2014. Patients were randomized to receive caplacizumab (n=36) or placebo (n=39).

All patients also received the current standard of care, which is, primarily, multiple PEs. The protocol for the study was adapted in September 2013 to allow 1 day of PE prior to study enrollment.

Patients in the caplacizumab arm immediately received an intravenous bolus dose of 10 mg and then a 10 mg subcutaneous dose of the drug daily until 30 days had elapsed after the final PE. Patients in the control arm received placebo at the same time points.

Platelet responses and relapse

The study’s primary endpoint was the time to platelet normalization. And patients in the caplacizumab arm achieved platelet normalization at more than twice the rate of patients in the placebo arm (overall hazard rate ratio=2.2, P=0.005).

Among patients with no prior PE, the median time to platelet normalization was 3 days in caplacizumab-treated patients (n=34) and 4.9 days in controls (n=35). Among patients with 1 prior PE, the median time to platelet normalization was 2.4 days in the caplacizumab arm (n=2) and 4.3 days in the placebo arm (n=4).

In the caplacizumab arm, a higher proportion of patients achieved a complete remission, and fewer patients had exacerbations of TTP. The complete remission rates were 81% and 46%, respectively. And the exacerbation rates were 8% and 28%, respectively.

However, the rate of exacerbation and/or relapse at up to 1 month of follow-up was the same in both arms, at 28%.

Seven patients relapsed within 10 days of stopping caplacizumab. All of these patients had continuous low ADAMTS13 activity (<10%) during and near the end of treatment.

Cardiac, renal, and tissue responses

Additional analyses revealed that patients in the caplacizumab arm had a faster time to troponin normalization than those in the placebo arm. At baseline, 53% of caplacizumab-treated patients and 46% of controls had elevated troponin. The median time to normalization was 9 days and 27 days, respectively.

Patients in the caplacizumab arm also had a faster time to creatinine normalization than those in the placebo arm. At baseline, 31% of caplacizumab-treated patients and 41% of controls had elevated creatinine. The median time to normalization was 4 days and 6 days, respectively.

And patients in the caplacizumab arm had a faster time to LDH normalization than those in the placebo arm. At baseline, 91% of caplacizumab-treated patients and 87% of controls had elevated LDH. The median time to normalization was 3 days and 4 days, respectively.

However, the investigators said they could not rule out a possible effect of PE therapy on LDH, creatinine, and troponin levels.

Need for PE

Results showed that caplacizumab could reduce the need for PE, at least while patients continued to receive the drug.

Patients in the caplacizumab arm required fewer PEs during the daily PE treatment period and the overall treatment period. But this benefit was lost during the 1-month follow-up period, which is reflective of the increased number of relapses, according to the investigators.

During the daily PE treatment period, the mean number of PE days was 5.9 in the caplacizumab arm and 7.9 in the placebo arm. During the overall treatment period, it was 7.7 and 11.7 days, respectively. And during the overall treatment and follow-up period, it was 10.2 and 11.7 days, respectively.

Adverse events

The investigators said caplacizumab increased the risk of bleeding events, but these were readily managed.

Treatment-emergent adverse events (AEs) occurred in 97% of patients in the caplacizumab arm and 100% of patients in the placebo arm. Eight percent of caplacizumab-treated patients discontinued treatment due to AEs, but none of the controls did.

Fifty-four percent of patients in the caplacizumab arm had a bleeding event, as did 38% of patients in the placebo arm. Eighty percent of the bleeding events in the caplacizumab arm were mild. Three patients required drug treatment. None required von Willebrand factor or factor VIII substitution.

Serious AEs occurred in 57% of caplacizumab-treated patients and 51% of controls. Serious bleeding events occurred in 6% and 5%, respectively.

Micrograph showing TTP

Image by Erhabor Osaro

TORONTO—Adding the anti-von Willebrand factor nanobody caplacizumab to standard therapy can provide clinical benefits for patients with

acquired thrombotic thrombocytopenic purpura (TTP), according to research presented at the 2015 ISTH Congress.

In the phase 2 TITAN trial, patients who received caplacizumab and standard therapy had a significantly shorter time to platelet normalization than patients who received standard therapy and placebo.

Caplacizumab was also associated with a shorter time to troponin, creatinine, and lactate dehydrogenase (LDH) normalization, as well as a reduced need for plasma exchange (PE).

However, some patients relapsed after stopping caplacizumab, and the majority of these relapses could be linked to unresolved disease activity. The drug also increased the risk of mild-to-moderate bleeding compared to placebo.

Flora Peyvandi, MD, PhD, of the University of Milan in Italy, presented data from the TITAN trial at ISTH as abstract LB006. Information on using ADAMTS13 activity for treatment monitoring in the TITAN trial was also presented at the meeting, as abstract OR363.

TITAN was sponsored by Ablynx, the company developing caplacizumab.

The study enrolled 75 patients with acquired TTP from January 2011 to January 2014. Patients were randomized to receive caplacizumab (n=36) or placebo (n=39).

All patients also received the current standard of care, which is, primarily, multiple PEs. The protocol for the study was adapted in September 2013 to allow 1 day of PE prior to study enrollment.

Patients in the caplacizumab arm immediately received an intravenous bolus dose of 10 mg and then a 10 mg subcutaneous dose of the drug daily until 30 days had elapsed after the final PE. Patients in the control arm received placebo at the same time points.

Platelet responses and relapse

The study’s primary endpoint was the time to platelet normalization. And patients in the caplacizumab arm achieved platelet normalization at more than twice the rate of patients in the placebo arm (overall hazard rate ratio=2.2, P=0.005).

Among patients with no prior PE, the median time to platelet normalization was 3 days in caplacizumab-treated patients (n=34) and 4.9 days in controls (n=35). Among patients with 1 prior PE, the median time to platelet normalization was 2.4 days in the caplacizumab arm (n=2) and 4.3 days in the placebo arm (n=4).

In the caplacizumab arm, a higher proportion of patients achieved a complete remission, and fewer patients had exacerbations of TTP. The complete remission rates were 81% and 46%, respectively. And the exacerbation rates were 8% and 28%, respectively.

However, the rate of exacerbation and/or relapse at up to 1 month of follow-up was the same in both arms, at 28%.

Seven patients relapsed within 10 days of stopping caplacizumab. All of these patients had continuous low ADAMTS13 activity (<10%) during and near the end of treatment.

Cardiac, renal, and tissue responses

Additional analyses revealed that patients in the caplacizumab arm had a faster time to troponin normalization than those in the placebo arm. At baseline, 53% of caplacizumab-treated patients and 46% of controls had elevated troponin. The median time to normalization was 9 days and 27 days, respectively.

Patients in the caplacizumab arm also had a faster time to creatinine normalization than those in the placebo arm. At baseline, 31% of caplacizumab-treated patients and 41% of controls had elevated creatinine. The median time to normalization was 4 days and 6 days, respectively.

And patients in the caplacizumab arm had a faster time to LDH normalization than those in the placebo arm. At baseline, 91% of caplacizumab-treated patients and 87% of controls had elevated LDH. The median time to normalization was 3 days and 4 days, respectively.

However, the investigators said they could not rule out a possible effect of PE therapy on LDH, creatinine, and troponin levels.

Need for PE

Results showed that caplacizumab could reduce the need for PE, at least while patients continued to receive the drug.

Patients in the caplacizumab arm required fewer PEs during the daily PE treatment period and the overall treatment period. But this benefit was lost during the 1-month follow-up period, which is reflective of the increased number of relapses, according to the investigators.

During the daily PE treatment period, the mean number of PE days was 5.9 in the caplacizumab arm and 7.9 in the placebo arm. During the overall treatment period, it was 7.7 and 11.7 days, respectively. And during the overall treatment and follow-up period, it was 10.2 and 11.7 days, respectively.

Adverse events

The investigators said caplacizumab increased the risk of bleeding events, but these were readily managed.

Treatment-emergent adverse events (AEs) occurred in 97% of patients in the caplacizumab arm and 100% of patients in the placebo arm. Eight percent of caplacizumab-treated patients discontinued treatment due to AEs, but none of the controls did.

Fifty-four percent of patients in the caplacizumab arm had a bleeding event, as did 38% of patients in the placebo arm. Eighty percent of the bleeding events in the caplacizumab arm were mild. Three patients required drug treatment. None required von Willebrand factor or factor VIII substitution.

Serious AEs occurred in 57% of caplacizumab-treated patients and 51% of controls. Serious bleeding events occurred in 6% and 5%, respectively.

Micrograph showing TTP

Image by Erhabor Osaro

TORONTO—Adding the anti-von Willebrand factor nanobody caplacizumab to standard therapy can provide clinical benefits for patients with

acquired thrombotic thrombocytopenic purpura (TTP), according to research presented at the 2015 ISTH Congress.

In the phase 2 TITAN trial, patients who received caplacizumab and standard therapy had a significantly shorter time to platelet normalization than patients who received standard therapy and placebo.

Caplacizumab was also associated with a shorter time to troponin, creatinine, and lactate dehydrogenase (LDH) normalization, as well as a reduced need for plasma exchange (PE).

However, some patients relapsed after stopping caplacizumab, and the majority of these relapses could be linked to unresolved disease activity. The drug also increased the risk of mild-to-moderate bleeding compared to placebo.

Flora Peyvandi, MD, PhD, of the University of Milan in Italy, presented data from the TITAN trial at ISTH as abstract LB006. Information on using ADAMTS13 activity for treatment monitoring in the TITAN trial was also presented at the meeting, as abstract OR363.

TITAN was sponsored by Ablynx, the company developing caplacizumab.

The study enrolled 75 patients with acquired TTP from January 2011 to January 2014. Patients were randomized to receive caplacizumab (n=36) or placebo (n=39).

All patients also received the current standard of care, which is, primarily, multiple PEs. The protocol for the study was adapted in September 2013 to allow 1 day of PE prior to study enrollment.

Patients in the caplacizumab arm immediately received an intravenous bolus dose of 10 mg and then a 10 mg subcutaneous dose of the drug daily until 30 days had elapsed after the final PE. Patients in the control arm received placebo at the same time points.

Platelet responses and relapse

The study’s primary endpoint was the time to platelet normalization. And patients in the caplacizumab arm achieved platelet normalization at more than twice the rate of patients in the placebo arm (overall hazard rate ratio=2.2, P=0.005).

Among patients with no prior PE, the median time to platelet normalization was 3 days in caplacizumab-treated patients (n=34) and 4.9 days in controls (n=35). Among patients with 1 prior PE, the median time to platelet normalization was 2.4 days in the caplacizumab arm (n=2) and 4.3 days in the placebo arm (n=4).

In the caplacizumab arm, a higher proportion of patients achieved a complete remission, and fewer patients had exacerbations of TTP. The complete remission rates were 81% and 46%, respectively. And the exacerbation rates were 8% and 28%, respectively.

However, the rate of exacerbation and/or relapse at up to 1 month of follow-up was the same in both arms, at 28%.

Seven patients relapsed within 10 days of stopping caplacizumab. All of these patients had continuous low ADAMTS13 activity (<10%) during and near the end of treatment.

Cardiac, renal, and tissue responses

Additional analyses revealed that patients in the caplacizumab arm had a faster time to troponin normalization than those in the placebo arm. At baseline, 53% of caplacizumab-treated patients and 46% of controls had elevated troponin. The median time to normalization was 9 days and 27 days, respectively.

Patients in the caplacizumab arm also had a faster time to creatinine normalization than those in the placebo arm. At baseline, 31% of caplacizumab-treated patients and 41% of controls had elevated creatinine. The median time to normalization was 4 days and 6 days, respectively.

And patients in the caplacizumab arm had a faster time to LDH normalization than those in the placebo arm. At baseline, 91% of caplacizumab-treated patients and 87% of controls had elevated LDH. The median time to normalization was 3 days and 4 days, respectively.

However, the investigators said they could not rule out a possible effect of PE therapy on LDH, creatinine, and troponin levels.

Need for PE

Results showed that caplacizumab could reduce the need for PE, at least while patients continued to receive the drug.

Patients in the caplacizumab arm required fewer PEs during the daily PE treatment period and the overall treatment period. But this benefit was lost during the 1-month follow-up period, which is reflective of the increased number of relapses, according to the investigators.

During the daily PE treatment period, the mean number of PE days was 5.9 in the caplacizumab arm and 7.9 in the placebo arm. During the overall treatment period, it was 7.7 and 11.7 days, respectively. And during the overall treatment and follow-up period, it was 10.2 and 11.7 days, respectively.

Adverse events

The investigators said caplacizumab increased the risk of bleeding events, but these were readily managed.

Treatment-emergent adverse events (AEs) occurred in 97% of patients in the caplacizumab arm and 100% of patients in the placebo arm. Eight percent of caplacizumab-treated patients discontinued treatment due to AEs, but none of the controls did.

Fifty-four percent of patients in the caplacizumab arm had a bleeding event, as did 38% of patients in the placebo arm. Eighty percent of the bleeding events in the caplacizumab arm were mild. Three patients required drug treatment. None required von Willebrand factor or factor VIII substitution.

Serious AEs occurred in 57% of caplacizumab-treated patients and 51% of controls. Serious bleeding events occurred in 6% and 5%, respectively.

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

TORONTO – In atrial fibrillation (AF) patients who must discontinue dabigatran for elective surgery, the risk of both stroke and major bleeding can be reduced to low levels using a formalized strategy for stopping and then restarting anticoagulation, according to results of a prospective study presented at the International Society on Thrombosis and Haemostasis Congress.

Among key findings presented at a press conference at the ISTH 2015 Congress, no strokes were recorded in more than 500 patients managed with the protocol, and the major bleeding rate was less than 2%, reported the study’s principal investigator, Dr. Sam Schulman, professor of hematology and thromboembolism, McMaster University, Hamilton, Ont.

Data from this study (Circulation 2015) were reported at the press conference alongside a second study of perioperative warfarin management. Both studies are potentially practice changing, because they supply evidence-based guidance for anticoagulation in patients with AF.

Courtesy International Society of Thrombosis and Haemostasis

Based on the findings from these two studies, “it is important to get this message out” that there are now data available on which to base clinical decisions, reported Dr. Schulman, who is also president of the ISTH 2015 Congress. His data were presented alongside a study that found no benefit from heparin bridging in AF patients when warfarin was stopped 5 days in advance of surgery.

In the study presented by Dr. Schulman, 542 patients with AF who were on dabigatran and scheduled for elective surgery were managed on a prespecified protocol for risk assessment. The protocol provided a time for stopping dabigatran before surgery based on such factors as renal function and procedure-related bleeding risk. Dabigatran was restarted after surgery on prespecified measures of surgery complexity and severity of consequences if bleeding occurred.

The primary outcome evaluated in the study was major bleeding in the first 30 days. Other outcomes of interest included thromboembolic complications, death and minor bleeding.

Major bleeding was observed in 1.8% of patients, a rate that Dr. Schulman characterized as “low and acceptable” in the context of expected background bleeding rates. There were four deaths, but all were unrelated to either bleeding or arterial thromboembolism. The only thromboembolic complication was a single transient ischemic attack. Minor bleeding occurred in 5.2%.

On the basis of the protocol, about half of the patients discontinued dabigatran 24 hours before surgery. No patient discontinued therapy more than 96 hours prior to surgery. The median time to resumption of dabigatran after surgery was 1 day, but the point at which it was restarted ranged between hours and 2 days. Bridging, which describes the injection of heparin for short-term anticoagulation, was not employed preoperatively but was used in 1.7% of cases postoperatively.

At the press conference, data also were reported from the BRIDGE study. That study, published online in the New England Journal of Medicine (2015 June 22; epub ahead of print ), found that bridging was not an effective strategy in AF patients who discontinue warfarin prior to elective surgery. In the press conference, Dr. Thomas L. Ortel, hematology/oncology division, Duke University Medical Center, Durham, N.C., agreed with Dr. Schulman that this is an area where evidence is needed to guide care.

In the absence of data, “physicians do whatever they think is best,” Dr. Schulman noted at the press conference. Referring to strategies for stopping anticoagulants for surgery in patients with AF, Dr. Schulman said, “some of them stop the blood thinner too early because they are afraid that the patient is going to bleed during surgery and instead the patient can have a stroke. Some stop too late, and the patient can have bleeding.”

The data presented at the meeting provide an evidence base for clinical decisions. Dr. Schulman suggested that these data are meaningful for guiding care.

Dr. Ortel disclosed grant/research support from Eisai and Pfizer. Dr. Schulman had no disclosures.

Patient undergoing CT scan

Photo by Angela Mary Butler

TORONTO—A CT scan of the abdomen and pelvis does not improve cancer detection in people with unexplained venous thromboembolism (VTE), results of the SOME trial suggest.

“Unexplained blood clots have long been thought of as a possible early warning sign of cancer, with previous studies suggesting that up to 10% of patients with unexplained clots will be diagnosed with cancer within the year,” said Marc Carrier, MD, of Ottawa Hospital Research Institute in Ontario, Canada.

“Some clinical guidelines recommend a CT scan of the abdomen and pelvis in these patients, in addition to other cancer screening, but there has been very little evidence to know if the added CT scan is helpful. We did this study to find out.”

Dr Carrier and his colleagues described this research in an article published in NEJM and in a presentation given at the 2015 ISTH Congress (abstract LB001*).

The trial involved 854 patients treated at 9 Canadian centers who had an unexplained VTE—deep vein thrombosis, pulmonary embolism, or both.

The patients were randomized to receive basic cancer screening or basic cancer screening plus a CT scan of the abdomen and pelvis. Basic cancer screening included blood work and a chest X-ray, in addition to gender-specific screening (such as a breast exam, Pap smear, and prostate exam) if it had not been conducted in the last year.

Overall, 33 patients (3.9%) had a new diagnosis of occult cancer during the 1-year follow-up period.

There was no significant difference in the rate of diagnosis between the patients who received only basic screening and the patients who underwent CT as well—3.2% (14/431) and 4.5% (19/423), respectively (P=0.28).

Likewise, there was no significant difference in the number of cancers that were not diagnosed by the screening strategies. Basic screening failed to uncover 4 cancers (29%), and basic screening plus CT failed to reveal 5 cancers (26%, P=1.0).

In addition, there was no significant difference between the screening strategies in the time to cancer diagnosis or cancer-related mortality. The mean time to cancer diagnosis was 4.2 months in the basic screening group and 4.0 months in the CT group (P=0.88). And the rate of cancer-related mortality was 1.4% and 0.9%, respectively (P=0.75).

“Although it is tempting to believe that more cancer screening is always better, our study shows that this is not necessarily the case,” Dr Carrier said. “And in fact, unnecessary CT scanning has real risks. It can cause stress and anxiety in patients, as well as radiation exposure, and it can lead to over-investigation of false-positive findings. Our study means many patients will now be able to avoid this.”

That could lead to significant savings for the healthcare system, according to the researchers. For example, approximately 30,000 Canadians suffer from an unexplained VTE every year, and a CT scan costs approximately $300. So avoiding unnecessary CT scans could result in a potential saving of $9 million per year in Canada alone.

*Information in the abstract differs from that presented at the meeting.

Patient undergoing CT scan

Photo by Angela Mary Butler

TORONTO—A CT scan of the abdomen and pelvis does not improve cancer detection in people with unexplained venous thromboembolism (VTE), results of the SOME trial suggest.

“Unexplained blood clots have long been thought of as a possible early warning sign of cancer, with previous studies suggesting that up to 10% of patients with unexplained clots will be diagnosed with cancer within the year,” said Marc Carrier, MD, of Ottawa Hospital Research Institute in Ontario, Canada.

“Some clinical guidelines recommend a CT scan of the abdomen and pelvis in these patients, in addition to other cancer screening, but there has been very little evidence to know if the added CT scan is helpful. We did this study to find out.”

Dr Carrier and his colleagues described this research in an article published in NEJM and in a presentation given at the 2015 ISTH Congress (abstract LB001*).

The trial involved 854 patients treated at 9 Canadian centers who had an unexplained VTE—deep vein thrombosis, pulmonary embolism, or both.

The patients were randomized to receive basic cancer screening or basic cancer screening plus a CT scan of the abdomen and pelvis. Basic cancer screening included blood work and a chest X-ray, in addition to gender-specific screening (such as a breast exam, Pap smear, and prostate exam) if it had not been conducted in the last year.

Overall, 33 patients (3.9%) had a new diagnosis of occult cancer during the 1-year follow-up period.

There was no significant difference in the rate of diagnosis between the patients who received only basic screening and the patients who underwent CT as well—3.2% (14/431) and 4.5% (19/423), respectively (P=0.28).

Likewise, there was no significant difference in the number of cancers that were not diagnosed by the screening strategies. Basic screening failed to uncover 4 cancers (29%), and basic screening plus CT failed to reveal 5 cancers (26%, P=1.0).

In addition, there was no significant difference between the screening strategies in the time to cancer diagnosis or cancer-related mortality. The mean time to cancer diagnosis was 4.2 months in the basic screening group and 4.0 months in the CT group (P=0.88). And the rate of cancer-related mortality was 1.4% and 0.9%, respectively (P=0.75).

“Although it is tempting to believe that more cancer screening is always better, our study shows that this is not necessarily the case,” Dr Carrier said. “And in fact, unnecessary CT scanning has real risks. It can cause stress and anxiety in patients, as well as radiation exposure, and it can lead to over-investigation of false-positive findings. Our study means many patients will now be able to avoid this.”

That could lead to significant savings for the healthcare system, according to the researchers. For example, approximately 30,000 Canadians suffer from an unexplained VTE every year, and a CT scan costs approximately $300. So avoiding unnecessary CT scans could result in a potential saving of $9 million per year in Canada alone.

*Information in the abstract differs from that presented at the meeting.

Patient undergoing CT scan

Photo by Angela Mary Butler

TORONTO—A CT scan of the abdomen and pelvis does not improve cancer detection in people with unexplained venous thromboembolism (VTE), results of the SOME trial suggest.

“Unexplained blood clots have long been thought of as a possible early warning sign of cancer, with previous studies suggesting that up to 10% of patients with unexplained clots will be diagnosed with cancer within the year,” said Marc Carrier, MD, of Ottawa Hospital Research Institute in Ontario, Canada.

“Some clinical guidelines recommend a CT scan of the abdomen and pelvis in these patients, in addition to other cancer screening, but there has been very little evidence to know if the added CT scan is helpful. We did this study to find out.”

Dr Carrier and his colleagues described this research in an article published in NEJM and in a presentation given at the 2015 ISTH Congress (abstract LB001*).

The trial involved 854 patients treated at 9 Canadian centers who had an unexplained VTE—deep vein thrombosis, pulmonary embolism, or both.

The patients were randomized to receive basic cancer screening or basic cancer screening plus a CT scan of the abdomen and pelvis. Basic cancer screening included blood work and a chest X-ray, in addition to gender-specific screening (such as a breast exam, Pap smear, and prostate exam) if it had not been conducted in the last year.

Overall, 33 patients (3.9%) had a new diagnosis of occult cancer during the 1-year follow-up period.

There was no significant difference in the rate of diagnosis between the patients who received only basic screening and the patients who underwent CT as well—3.2% (14/431) and 4.5% (19/423), respectively (P=0.28).

Likewise, there was no significant difference in the number of cancers that were not diagnosed by the screening strategies. Basic screening failed to uncover 4 cancers (29%), and basic screening plus CT failed to reveal 5 cancers (26%, P=1.0).

In addition, there was no significant difference between the screening strategies in the time to cancer diagnosis or cancer-related mortality. The mean time to cancer diagnosis was 4.2 months in the basic screening group and 4.0 months in the CT group (P=0.88). And the rate of cancer-related mortality was 1.4% and 0.9%, respectively (P=0.75).

“Although it is tempting to believe that more cancer screening is always better, our study shows that this is not necessarily the case,” Dr Carrier said. “And in fact, unnecessary CT scanning has real risks. It can cause stress and anxiety in patients, as well as radiation exposure, and it can lead to over-investigation of false-positive findings. Our study means many patients will now be able to avoid this.”

That could lead to significant savings for the healthcare system, according to the researchers. For example, approximately 30,000 Canadians suffer from an unexplained VTE every year, and a CT scan costs approximately $300. So avoiding unnecessary CT scans could result in a potential saving of $9 million per year in Canada alone.

*Information in the abstract differs from that presented at the meeting.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

TORONTO – Idarucizumab is a promising agent that quickly and safely reverses the anticoagulant effects of dabigatran whether the goal is to control serious bleeding or to permit urgent surgery, according to interim results of a multicenter trial.

Idarucizumab is a monoclonal antibody that binds to dabigatran to reverse its activity. The data, presented by Dr. V. Charles Pollack Jr. at the International Society on Thrombosis and Haemostasis congress, involved the first 90 patients of an ongoing trial with a planned enrollment of 300. The data from this trial, called REVERSE-AD, were published online simultaneously with the June 22 presentation at the congress (N. Engl. J. Med 2015 [doi:10.1056/NEJMoa1502000]).

Courtesy International Society on Thrombosis and Haemostasis

“Non–vitamin K antagonist oral anticoagulants (NOACs) are generally safer than warfarin, and provide similar or improved efficacy in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of venous thromboembolism,” Dr. Pollack said in an interview. “Nonetheless, serious bleeding events may occur with NOAC use, and patients taking one of these agents occasionally require urgent surgery or other intervention for which normal hemostasis is required,” added Dr. Pollack, chair of the department of emergency medicine at Pennsylvania Hospital in Philadelphia.

In RE-VERSE AD (a study of the reversal effects of idarucizumab on active dabigatran), the first 90 patients were divided into two distinct groups. Group A, with 51 patients, included those on dabigatran with serious bleeding. Group B, with 39 patients, required reversal of dabigatran for urgent or emergent procedures. In both, idarucizumab provided a median maximum reversal of 100% (95% confidence interval, 100-100) of the anticoagulation effect within 4 hours.

Clotting assays were normalized almost immediately in almost 90% of patients, and the effect was durable, with 80% having measured dabigatran levels reflecting no significant anticoagulation 24 hours later, Dr. Pollack said.

“Clinical outcomes were quite good in this multimorbid patient population, with restoration of hemostasis as reported by local investigators achieved in less than 12 hours when assessable, and with 92% of surgical patients being reported as having normal hemostasis at the time of the procedure,” he said.

Idarucizumab was generally well tolerated in the patient population. “There were no serious adverse events related to the reversal agent ... and only one patient experienced a thrombotic complication within 72 hours, and that patient had not been restarted on any antithrombotic medications,” Dr. Pollack said.

“The study is ongoing,” he added, “but these interim results show rather convincingly that idarucizumab completely and safely reverses the anticoagulant effects of dabigatran within minutes.”

In addition, Dr. Pollack said the availability of a specific reversal agent for dabigatran would enhance its safety margin, and thus alleviate the fears of providers who may hesitate to use a NOAC because of the lack of an “antidote.”

“In fact, most such cases can already be successfully and safely managed with general support and ‘tincture of time’ (the half-life of dabigatran is much shorter than that of warfarin), but having a specific ‘go-to’ option could streamline the care of the most significantly compromised patients,” he said.

Dr. Pollack emphasized, however, that idarucizumab is a specific reversal agent for dabigatran, not an antidote. “To me, the latter would imply that idarucizumab immediately stops bleeding associated with active use of dabigatran,” he said.

Providers should realize that while idarucizumab seems capable of removing dabigatran-induced coagulopathy from the list of concerns when managing a patient with serious bleeding or before a “sharp” procedure, bleeding is a multifaceted issue that also may be due to traumatized blood vessels, other causes of coagulopathy such as liver disease, or concurrent use of antiplatelet medications, he said.

“The patient with a serious or life-threatening bleed on dabigatran will likely need additional care to investigate and manage such concerns,” Dr. Pollack said. “But at least idarucizumab can specifically, safely, and rapidly address the primary consideration.

“The safety of anticoagulation therapy with dabigatran is further enhanced with idarucizumab, a specific reversal agent that won’t need to be used often, but the availability of which would be reassuring to prescribers,” he concluded.

Boehringer Ingelheim sponsored RE-VERSE AD. Idarucizumab was given a fast-track status by the Food and Drug Administration, and BI submitted a new drug application in March 2015, according to the company.

Dr. Pollack reported receiving personal fees from BI, Janssen, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Disclosures for all the investigators are available at NEJM.org.

TORONTO—Interim results of a phase 3 study suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of

dabigatran in real-world situations.

In the RE-VERSE AD trial, idarucizumab normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

In addition, researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

These results have been published in NEJM and presented at the 2015 ISTH Congress (abstract LB005). The study was sponsored by Boehringer Ingelheim, the company developing idarucizumab and dabigatran.

“The interim analysis from RE-VERSE AD is important for healthcare professionals as it provides the first insights into the effect of a specific reversal agent to a non-vitamin K antagonist oral anticoagulant during real-world emergency situations,” said study investigator Charles Pollack, MD, of the University of Pennsylvania in Philadelphia.

Because RE-VERSE AD was designed to evaluate how idarucizumab would perform in real-world situations, severely ill or injured patients were eligible for enrollment. The interim analysis included data from 90 patients in emergency settings who were taking dabigatran and required reversal.

The patients were divided into 2 groups: those with uncontrolled or life-threatening bleeding complications, such as intracranial hemorrhage or severe trauma (group A, n=51), and patients requiring emergency surgery or an invasive procedure (group B, n=39).

The primary endpoint of the study is the degree to which 5 g of idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.

The researchers were able to evaluate the percentage of reversal by dTT in 68 patients (40 in group A and 28 in group B) and the percentage of reversal by ECT in 81 patients (47 in group A and 34 in group B).

The dTT was normalized in 98% of evaluable patients in group A and 93% in group B. The ECT was normalized in 89% of evaluable patients in group A and 88% in group B.

At 12 hours and 24 hours, the dTT was below the upper limit of the normal range in 90% of evaluable patients in group A and 81% in group B. The ECT was below the upper limit of the normal range in 72% of evaluable group A patients and 54% of evaluable group B patients.

Among the 35 evaluable patients in group A, hemostasis was restored at a median of 11.4 hours. Among the 36 patients in group B who underwent a procedure, 33 had normal intraoperative hemostasis. Two patients had mildly abnormal hemostasis, and 1 patient had moderately abnormal hemostasis.

“As observed in earlier research in volunteers, idarucizumab reversed the anticoagulant effect of dabigatran in patients completely within minutes, even in those rare critical care situations studied in RE-VERSE AD,” Dr Pollack said.

“These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.”

Twenty-one patients (13 in group A and 8 in group B) experienced serious adverse events during the study.

This included 18 events that led to death, 5 thrombotic events, 2 cases of gastrointestinal hemorrhage, a postoperative wound infection, a case of delirium, a case of right ventricular failure, and a case of pulmonary edema. (Some patients had more than one serious adverse event.)

TORONTO—Interim results of a phase 3 study suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of

dabigatran in real-world situations.

In the RE-VERSE AD trial, idarucizumab normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

In addition, researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

These results have been published in NEJM and presented at the 2015 ISTH Congress (abstract LB005). The study was sponsored by Boehringer Ingelheim, the company developing idarucizumab and dabigatran.

“The interim analysis from RE-VERSE AD is important for healthcare professionals as it provides the first insights into the effect of a specific reversal agent to a non-vitamin K antagonist oral anticoagulant during real-world emergency situations,” said study investigator Charles Pollack, MD, of the University of Pennsylvania in Philadelphia.

Because RE-VERSE AD was designed to evaluate how idarucizumab would perform in real-world situations, severely ill or injured patients were eligible for enrollment. The interim analysis included data from 90 patients in emergency settings who were taking dabigatran and required reversal.

The patients were divided into 2 groups: those with uncontrolled or life-threatening bleeding complications, such as intracranial hemorrhage or severe trauma (group A, n=51), and patients requiring emergency surgery or an invasive procedure (group B, n=39).

The primary endpoint of the study is the degree to which 5 g of idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.

The researchers were able to evaluate the percentage of reversal by dTT in 68 patients (40 in group A and 28 in group B) and the percentage of reversal by ECT in 81 patients (47 in group A and 34 in group B).

The dTT was normalized in 98% of evaluable patients in group A and 93% in group B. The ECT was normalized in 89% of evaluable patients in group A and 88% in group B.

At 12 hours and 24 hours, the dTT was below the upper limit of the normal range in 90% of evaluable patients in group A and 81% in group B. The ECT was below the upper limit of the normal range in 72% of evaluable group A patients and 54% of evaluable group B patients.

Among the 35 evaluable patients in group A, hemostasis was restored at a median of 11.4 hours. Among the 36 patients in group B who underwent a procedure, 33 had normal intraoperative hemostasis. Two patients had mildly abnormal hemostasis, and 1 patient had moderately abnormal hemostasis.

“As observed in earlier research in volunteers, idarucizumab reversed the anticoagulant effect of dabigatran in patients completely within minutes, even in those rare critical care situations studied in RE-VERSE AD,” Dr Pollack said.

“These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.”

Twenty-one patients (13 in group A and 8 in group B) experienced serious adverse events during the study.

This included 18 events that led to death, 5 thrombotic events, 2 cases of gastrointestinal hemorrhage, a postoperative wound infection, a case of delirium, a case of right ventricular failure, and a case of pulmonary edema. (Some patients had more than one serious adverse event.)

TORONTO—Interim results of a phase 3 study suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of

dabigatran in real-world situations.

In the RE-VERSE AD trial, idarucizumab normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

In addition, researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

These results have been published in NEJM and presented at the 2015 ISTH Congress (abstract LB005). The study was sponsored by Boehringer Ingelheim, the company developing idarucizumab and dabigatran.

“The interim analysis from RE-VERSE AD is important for healthcare professionals as it provides the first insights into the effect of a specific reversal agent to a non-vitamin K antagonist oral anticoagulant during real-world emergency situations,” said study investigator Charles Pollack, MD, of the University of Pennsylvania in Philadelphia.

Because RE-VERSE AD was designed to evaluate how idarucizumab would perform in real-world situations, severely ill or injured patients were eligible for enrollment. The interim analysis included data from 90 patients in emergency settings who were taking dabigatran and required reversal.

The patients were divided into 2 groups: those with uncontrolled or life-threatening bleeding complications, such as intracranial hemorrhage or severe trauma (group A, n=51), and patients requiring emergency surgery or an invasive procedure (group B, n=39).

The primary endpoint of the study is the degree to which 5 g of idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.

The researchers were able to evaluate the percentage of reversal by dTT in 68 patients (40 in group A and 28 in group B) and the percentage of reversal by ECT in 81 patients (47 in group A and 34 in group B).

The dTT was normalized in 98% of evaluable patients in group A and 93% in group B. The ECT was normalized in 89% of evaluable patients in group A and 88% in group B.

At 12 hours and 24 hours, the dTT was below the upper limit of the normal range in 90% of evaluable patients in group A and 81% in group B. The ECT was below the upper limit of the normal range in 72% of evaluable group A patients and 54% of evaluable group B patients.

Among the 35 evaluable patients in group A, hemostasis was restored at a median of 11.4 hours. Among the 36 patients in group B who underwent a procedure, 33 had normal intraoperative hemostasis. Two patients had mildly abnormal hemostasis, and 1 patient had moderately abnormal hemostasis.

“As observed in earlier research in volunteers, idarucizumab reversed the anticoagulant effect of dabigatran in patients completely within minutes, even in those rare critical care situations studied in RE-VERSE AD,” Dr Pollack said.

“These data demonstrate that use of idarucizumab can help physicians focus on other vital aspects of emergency management beyond anticoagulant reversal in dabigatran-treated patients.”

Twenty-one patients (13 in group A and 8 in group B) experienced serious adverse events during the study.

This included 18 events that led to death, 5 thrombotic events, 2 cases of gastrointestinal hemorrhage, a postoperative wound infection, a case of delirium, a case of right ventricular failure, and a case of pulmonary edema. (Some patients had more than one serious adverse event.)

Warfarin tablets

TORONTO—Bridge anticoagulant therapy appears to be unnecessary in patients with atrial fibrillation (AFib) undergoing elective surgery, according to researchers.

In the BRIDGE study, AFib patients who stopped all anticoagulant therapy before elective surgery had no higher risk of thrombosis and a lower risk of major bleeding than patients who were given bridge therapy with low-molecular weight heparin after stopping warfarin.

This research was presented at the 2015 ISTH Congress (abstract LB002) and published in NEJM.

“Bridging has been controversial because there has been a lack of data demonstrating that it’s necessary, so people don’t know what to do,” said study author Thomas L. Ortel, MD, PhD, of Duke University Medical Center in Durham, North Carolina.

“You can go to 5 different doctors, and some will bridge, and others won’t. It just depends on what they feel they can safely do. This trial gives a firm answer to that question.”

The trial enrolled 1884 patients with AFib and atrial flutter. Roughly half received bridge therapy with dalteparin, and the other half received a placebo while halting their warfarin for up to 13 days around their elective surgeries. Patients were followed for up to 37 days after their procedures.

Among patients who stopped all anticoagulant therapy, the incidence of arterial thrombosis was 0.4%, compared to 0.3% for patients who received bridge therapy (P=0.01 for noninferiority).

Major bleeding events were significantly less common among the non-bridging group. They occurred in 1.3% of patients who were not on anticoagulant therapy and 3.2% of patients who received bridge therapy (P=0.005 for superiority).

“Bridging does not improve the outcome for stroke prevention but increases the risk of major bleeding complications,” Dr Ortel said. “That’s the counter balance. We’re not doing patients any good, and we are potentially hurting them.”

Dr Ortel noted that these findings are specific to AFib patients who take warfarin and should not be generalized to other types of patients or other anticoagulants. But the results will be taken into consideration by organizations that develop guidelines.

“This is the first study to provide high-quality clinical trial data demonstrating that, for patients with atrial fibrillation who need a procedure and who need to come off warfarin, they can simply stop and restart,” Dr Ortel said. “They do not need to be bridged.”

Warfarin tablets

TORONTO—Bridge anticoagulant therapy appears to be unnecessary in patients with atrial fibrillation (AFib) undergoing elective surgery, according to researchers.

In the BRIDGE study, AFib patients who stopped all anticoagulant therapy before elective surgery had no higher risk of thrombosis and a lower risk of major bleeding than patients who were given bridge therapy with low-molecular weight heparin after stopping warfarin.

This research was presented at the 2015 ISTH Congress (abstract LB002) and published in NEJM.

“Bridging has been controversial because there has been a lack of data demonstrating that it’s necessary, so people don’t know what to do,” said study author Thomas L. Ortel, MD, PhD, of Duke University Medical Center in Durham, North Carolina.

“You can go to 5 different doctors, and some will bridge, and others won’t. It just depends on what they feel they can safely do. This trial gives a firm answer to that question.”

The trial enrolled 1884 patients with AFib and atrial flutter. Roughly half received bridge therapy with dalteparin, and the other half received a placebo while halting their warfarin for up to 13 days around their elective surgeries. Patients were followed for up to 37 days after their procedures.

Among patients who stopped all anticoagulant therapy, the incidence of arterial thrombosis was 0.4%, compared to 0.3% for patients who received bridge therapy (P=0.01 for noninferiority).

Major bleeding events were significantly less common among the non-bridging group. They occurred in 1.3% of patients who were not on anticoagulant therapy and 3.2% of patients who received bridge therapy (P=0.005 for superiority).

“Bridging does not improve the outcome for stroke prevention but increases the risk of major bleeding complications,” Dr Ortel said. “That’s the counter balance. We’re not doing patients any good, and we are potentially hurting them.”

Dr Ortel noted that these findings are specific to AFib patients who take warfarin and should not be generalized to other types of patients or other anticoagulants. But the results will be taken into consideration by organizations that develop guidelines.

“This is the first study to provide high-quality clinical trial data demonstrating that, for patients with atrial fibrillation who need a procedure and who need to come off warfarin, they can simply stop and restart,” Dr Ortel said. “They do not need to be bridged.”

Warfarin tablets

TORONTO—Bridge anticoagulant therapy appears to be unnecessary in patients with atrial fibrillation (AFib) undergoing elective surgery, according to researchers.

In the BRIDGE study, AFib patients who stopped all anticoagulant therapy before elective surgery had no higher risk of thrombosis and a lower risk of major bleeding than patients who were given bridge therapy with low-molecular weight heparin after stopping warfarin.

This research was presented at the 2015 ISTH Congress (abstract LB002) and published in NEJM.

“Bridging has been controversial because there has been a lack of data demonstrating that it’s necessary, so people don’t know what to do,” said study author Thomas L. Ortel, MD, PhD, of Duke University Medical Center in Durham, North Carolina.

“You can go to 5 different doctors, and some will bridge, and others won’t. It just depends on what they feel they can safely do. This trial gives a firm answer to that question.”

The trial enrolled 1884 patients with AFib and atrial flutter. Roughly half received bridge therapy with dalteparin, and the other half received a placebo while halting their warfarin for up to 13 days around their elective surgeries. Patients were followed for up to 37 days after their procedures.

Among patients who stopped all anticoagulant therapy, the incidence of arterial thrombosis was 0.4%, compared to 0.3% for patients who received bridge therapy (P=0.01 for noninferiority).

Major bleeding events were significantly less common among the non-bridging group. They occurred in 1.3% of patients who were not on anticoagulant therapy and 3.2% of patients who received bridge therapy (P=0.005 for superiority).

“Bridging does not improve the outcome for stroke prevention but increases the risk of major bleeding complications,” Dr Ortel said. “That’s the counter balance. We’re not doing patients any good, and we are potentially hurting them.”

Dr Ortel noted that these findings are specific to AFib patients who take warfarin and should not be generalized to other types of patients or other anticoagulants. But the results will be taken into consideration by organizations that develop guidelines.

“This is the first study to provide high-quality clinical trial data demonstrating that, for patients with atrial fibrillation who need a procedure and who need to come off warfarin, they can simply stop and restart,” Dr Ortel said. “They do not need to be bridged.”