Procedure deemed unnecessary in most DVT patients

Image by Kevin MacKenzie

Researchers have found evidence to suggest that pharmacomechanical catheter-directed thrombolysis is largely inappropriate as first-line treatment for patients with acute proximal deep vein thrombosis (DVT).

The team found that anticoagulation plus pharmacomechanical thrombolysis was no more effective than anticoagulation alone for preventing post-thrombotic syndrome (PTS).

Additionally, patients who received pharmacomechanical thrombolysis had a higher risk of major bleeding.

The researchers reported these findings in NEJM.

The trial, known as the ATTRACT study, was designed to determine whether performing pharmacomechanical thrombolysis as part of initial treatment for patients with DVT would reduce the number of patients who later develop PTS.

“The clinical research in deep vein thrombosis and post-thrombotic syndrome is very important to the clinical community and of interest to the National Heart, Lung, and Blood Institute [NHLBI],” said Andrei Kindzelski, MD, PhD, the NHLBI program officer for the ATTRACT trial.

“This landmark study, conducted at 56 clinical sites, demonstrated, in an unbiased manner, no benefits of catheter-directed thrombolysis as a first-line deep vein thrombosis treatment, enabling patients to avoid an unnecessary medical procedure. At the same time, ATTRACT identified a potential future research need in more targeted use of catheter-directed thrombolysis in specific patient groups.”

The study included 692 patients who were randomized to receive anticoagulation alone or anticoagulation plus pharmacomechanical thrombolysis.

Anticoagulation consisted of unfractionated heparin, enoxaparin, dalteparin, or tinzaparin for at least 5 days, overlapped with long-term warfarin, as well as the prescription of elastic compression stockings.

Pharmacomechanical thrombolysis consisted of catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting.

Results

The study’s primary outcome was the development of PTS between 6 and 24 months of follow-up.

There was no significant difference in PTS incidence between the treatment arms. PTS occurred in 47% (157/336) of patients in the pharmacomechanical-thrombolysis group and 48% (171/355) of patients in the control group (risk ratio=0.96, P=0.56).

Pharmacomechanical thrombolysis did reduce the severity of PTS, however. The incidence of moderate-to-severe PTS was 24% in the control group and 18% in the pharmacomechanical-thrombolysis group (risk ratio=0.73; P=0.04).

Severity scores for PTS were significantly lower in the pharmacomechanical-thrombolysis group than the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for each time point).

There was no significant difference between the treatment arms in the incidence of recurrent venous thromboembolism (VTE) over the 24-month follow-up period. Recurrent VTE was observed in 12% of patients in the pharmacomechanical-thrombolysis group and 8% of controls (P=0.09).

On the other hand, there was a significant increase in the incidence of major bleeding within 10 days in the pharmacomechanical-thrombolysis group. The incidence was 1.7% (n=6) in the pharmacomechanical thrombolysis group and 0.3% (n=1) in the control group (P=0.049).

“None of us was surprised to find that this treatment [pharmacomechanical thrombolysis] is riskier than blood-thinning drugs alone,” said study author Suresh Vedantham, MD, of Washington University School of Medicine in St. Louis, Missouri.

“To justify that extra risk, we would have had to show a dramatic improvement in long-term outcomes, and the study didn’t show that. We saw some improvement in disease severity but not enough to justify the risks for most patients.”

While the results indicate that most patients should not undergo pharmacomechanical thrombolysis, the data also hint that the benefits may outweigh the risks in some patients, such as those with exceptionally large clots.

“This is the first large, rigorous study to examine the ability of imaging-guided treatment to address post-thrombotic syndrome,” Dr Vedantham said. “This study will advance patient care by helping many people avoid an unnecessary procedure.”

“The findings are also interesting because there is the suggestion that at least some patients may have benefited. Sorting that out is going to be very important.”

For now, pharmacomechanical thrombolysis should be reserved for use as a second-line treatment for some carefully selected patients who are experiencing particularly severe limitations of leg function from DVT and who are not responding to anticoagulation alone, Dr Vedantham added.

This research was sponsored by NHLBI. Additional funding was provided by Boston Scientific, Covidien (now Medtronic), and Genentech, which provided recombinant tissue plasminogen activator for the study. Compression stockings were donated by BSN Medical.

Image by Kevin MacKenzie

Researchers have found evidence to suggest that pharmacomechanical catheter-directed thrombolysis is largely inappropriate as first-line treatment for patients with acute proximal deep vein thrombosis (DVT).

The team found that anticoagulation plus pharmacomechanical thrombolysis was no more effective than anticoagulation alone for preventing post-thrombotic syndrome (PTS).

Additionally, patients who received pharmacomechanical thrombolysis had a higher risk of major bleeding.

The researchers reported these findings in NEJM.

The trial, known as the ATTRACT study, was designed to determine whether performing pharmacomechanical thrombolysis as part of initial treatment for patients with DVT would reduce the number of patients who later develop PTS.

“The clinical research in deep vein thrombosis and post-thrombotic syndrome is very important to the clinical community and of interest to the National Heart, Lung, and Blood Institute [NHLBI],” said Andrei Kindzelski, MD, PhD, the NHLBI program officer for the ATTRACT trial.

“This landmark study, conducted at 56 clinical sites, demonstrated, in an unbiased manner, no benefits of catheter-directed thrombolysis as a first-line deep vein thrombosis treatment, enabling patients to avoid an unnecessary medical procedure. At the same time, ATTRACT identified a potential future research need in more targeted use of catheter-directed thrombolysis in specific patient groups.”

The study included 692 patients who were randomized to receive anticoagulation alone or anticoagulation plus pharmacomechanical thrombolysis.

Anticoagulation consisted of unfractionated heparin, enoxaparin, dalteparin, or tinzaparin for at least 5 days, overlapped with long-term warfarin, as well as the prescription of elastic compression stockings.

Pharmacomechanical thrombolysis consisted of catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting.

Results

The study’s primary outcome was the development of PTS between 6 and 24 months of follow-up.

There was no significant difference in PTS incidence between the treatment arms. PTS occurred in 47% (157/336) of patients in the pharmacomechanical-thrombolysis group and 48% (171/355) of patients in the control group (risk ratio=0.96, P=0.56).

Pharmacomechanical thrombolysis did reduce the severity of PTS, however. The incidence of moderate-to-severe PTS was 24% in the control group and 18% in the pharmacomechanical-thrombolysis group (risk ratio=0.73; P=0.04).

Severity scores for PTS were significantly lower in the pharmacomechanical-thrombolysis group than the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for each time point).

There was no significant difference between the treatment arms in the incidence of recurrent venous thromboembolism (VTE) over the 24-month follow-up period. Recurrent VTE was observed in 12% of patients in the pharmacomechanical-thrombolysis group and 8% of controls (P=0.09).

On the other hand, there was a significant increase in the incidence of major bleeding within 10 days in the pharmacomechanical-thrombolysis group. The incidence was 1.7% (n=6) in the pharmacomechanical thrombolysis group and 0.3% (n=1) in the control group (P=0.049).

“None of us was surprised to find that this treatment [pharmacomechanical thrombolysis] is riskier than blood-thinning drugs alone,” said study author Suresh Vedantham, MD, of Washington University School of Medicine in St. Louis, Missouri.

“To justify that extra risk, we would have had to show a dramatic improvement in long-term outcomes, and the study didn’t show that. We saw some improvement in disease severity but not enough to justify the risks for most patients.”

While the results indicate that most patients should not undergo pharmacomechanical thrombolysis, the data also hint that the benefits may outweigh the risks in some patients, such as those with exceptionally large clots.

“This is the first large, rigorous study to examine the ability of imaging-guided treatment to address post-thrombotic syndrome,” Dr Vedantham said. “This study will advance patient care by helping many people avoid an unnecessary procedure.”

“The findings are also interesting because there is the suggestion that at least some patients may have benefited. Sorting that out is going to be very important.”

For now, pharmacomechanical thrombolysis should be reserved for use as a second-line treatment for some carefully selected patients who are experiencing particularly severe limitations of leg function from DVT and who are not responding to anticoagulation alone, Dr Vedantham added.

This research was sponsored by NHLBI. Additional funding was provided by Boston Scientific, Covidien (now Medtronic), and Genentech, which provided recombinant tissue plasminogen activator for the study. Compression stockings were donated by BSN Medical.

Image by Kevin MacKenzie

Researchers have found evidence to suggest that pharmacomechanical catheter-directed thrombolysis is largely inappropriate as first-line treatment for patients with acute proximal deep vein thrombosis (DVT).

The team found that anticoagulation plus pharmacomechanical thrombolysis was no more effective than anticoagulation alone for preventing post-thrombotic syndrome (PTS).

Additionally, patients who received pharmacomechanical thrombolysis had a higher risk of major bleeding.

The researchers reported these findings in NEJM.

The trial, known as the ATTRACT study, was designed to determine whether performing pharmacomechanical thrombolysis as part of initial treatment for patients with DVT would reduce the number of patients who later develop PTS.

“The clinical research in deep vein thrombosis and post-thrombotic syndrome is very important to the clinical community and of interest to the National Heart, Lung, and Blood Institute [NHLBI],” said Andrei Kindzelski, MD, PhD, the NHLBI program officer for the ATTRACT trial.

“This landmark study, conducted at 56 clinical sites, demonstrated, in an unbiased manner, no benefits of catheter-directed thrombolysis as a first-line deep vein thrombosis treatment, enabling patients to avoid an unnecessary medical procedure. At the same time, ATTRACT identified a potential future research need in more targeted use of catheter-directed thrombolysis in specific patient groups.”

The study included 692 patients who were randomized to receive anticoagulation alone or anticoagulation plus pharmacomechanical thrombolysis.

Anticoagulation consisted of unfractionated heparin, enoxaparin, dalteparin, or tinzaparin for at least 5 days, overlapped with long-term warfarin, as well as the prescription of elastic compression stockings.

Pharmacomechanical thrombolysis consisted of catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting.

Results

The study’s primary outcome was the development of PTS between 6 and 24 months of follow-up.

There was no significant difference in PTS incidence between the treatment arms. PTS occurred in 47% (157/336) of patients in the pharmacomechanical-thrombolysis group and 48% (171/355) of patients in the control group (risk ratio=0.96, P=0.56).

Pharmacomechanical thrombolysis did reduce the severity of PTS, however. The incidence of moderate-to-severe PTS was 24% in the control group and 18% in the pharmacomechanical-thrombolysis group (risk ratio=0.73; P=0.04).

Severity scores for PTS were significantly lower in the pharmacomechanical-thrombolysis group than the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for each time point).

There was no significant difference between the treatment arms in the incidence of recurrent venous thromboembolism (VTE) over the 24-month follow-up period. Recurrent VTE was observed in 12% of patients in the pharmacomechanical-thrombolysis group and 8% of controls (P=0.09).

On the other hand, there was a significant increase in the incidence of major bleeding within 10 days in the pharmacomechanical-thrombolysis group. The incidence was 1.7% (n=6) in the pharmacomechanical thrombolysis group and 0.3% (n=1) in the control group (P=0.049).

“None of us was surprised to find that this treatment [pharmacomechanical thrombolysis] is riskier than blood-thinning drugs alone,” said study author Suresh Vedantham, MD, of Washington University School of Medicine in St. Louis, Missouri.

“To justify that extra risk, we would have had to show a dramatic improvement in long-term outcomes, and the study didn’t show that. We saw some improvement in disease severity but not enough to justify the risks for most patients.”

While the results indicate that most patients should not undergo pharmacomechanical thrombolysis, the data also hint that the benefits may outweigh the risks in some patients, such as those with exceptionally large clots.

“This is the first large, rigorous study to examine the ability of imaging-guided treatment to address post-thrombotic syndrome,” Dr Vedantham said. “This study will advance patient care by helping many people avoid an unnecessary procedure.”

“The findings are also interesting because there is the suggestion that at least some patients may have benefited. Sorting that out is going to be very important.”

For now, pharmacomechanical thrombolysis should be reserved for use as a second-line treatment for some carefully selected patients who are experiencing particularly severe limitations of leg function from DVT and who are not responding to anticoagulation alone, Dr Vedantham added.

This research was sponsored by NHLBI. Additional funding was provided by Boston Scientific, Covidien (now Medtronic), and Genentech, which provided recombinant tissue plasminogen activator for the study. Compression stockings were donated by BSN Medical.