Clot busting with catheter no better than anticoagulants for DVT
Clearing blood clot by means of pharmacomechanical catheter-directed thrombolysis, ie, blood clot removal with specialized devices which also deliver fibrinolytic drug directly to the clot, in addition to standard of care with anticoagulation did not lower the risk of developing post-thrombotic syndrome (PTS) as previously believed, but instead, increased the risk of major bleeding in patients with acute proximal deep-vein thrombosis (DVT) compared with anticoagulation alone, according to the ATTRACT* trial.
“What we know now is that we can spare most patients the need to undergo a risky and costly treatment,” said lead author and study principal investigator Professor Suresh Vedantham of Washington University School of Medicine in St. Louis, Louis, Missouri, US.
Over 2 years of follow-up, the primary outcome of PTS incidence was similar between the pharmacomechanical thrombolysis vs the anticoagulation-alone control groups (47 percent vs 48 percent, risk ratio [RR], 0.96; p=0.56). [N Engl J Med 2017;377:2240-2252]
The rate of recurrent venous thromboembolism (VTE) was also not significantly different over 2 years (12 percent vs 8 percent; p=0.09).
However, early major bleeding events (within 10 days) were more common in the pharmacomechanical thrombolysis than the control groups (1.7 percent vs 0.3 percent; p=0.049).
“We are dealing with a very sharp double-edged sword here,” said Vedantham. “None of us was surprised to find that this treatment is riskier than blood-thinning drugs alone. 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.”
Pharmacomechanical thrombolysis led to reduced PTS severity compared with control at all visits between 6 and 24 months as assessed by the Villalta score and Venous Clinical Severity Score (VCSS; p=0.03 for the comparison at 24 months using VCSS, p≤0.01 for all other comparisons). Fewer patients experienced moderate-to-severe PTS with pharmacomechanical thrombolysis vs control (18 percent vs 24 percent, RR, 0.73; p=0.04).
Pharmacomechanical thrombolysis-treated patients also had less leg pain than controls at 10 days (p=0.02) and 30 days (p=0.03) based on the Likert pain scale.
Despite improvements in disease severity and leg pain, improvement in quality of life at 2 years from baseline were not significantly different between the two treatment groups.
Potential benefit to select patients
The multicentre, open-label, phase III trial randomized 692 patients (median age 53 years, 62 percent males) with acute proximal DVT in a 1:1 ratio to pharmacomechanical thrombolysis in addition to anticoagulation or anticoagulation alone.
According to the researchers, the finding that pharmacomechanical thrombolysis did not prevent PTS was consistent in per-protocol analyses as well as across all prespecified subgroups.
“This study will advance patient care by helping many people avoid an unnecessary procedure,” said Vedantham. “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.”
Based on secondary and subgroup analyses, patients with acute iliofemoral DVT or more severe symptoms might still benefit from pharmacomechanical thrombolysis, although the researchers cautioned that the study was not powered for secondary outcomes. Also, missing assessments of PTS and incomplete follow-up may limit the findings.
“The ATTRACT trial will provide crucial guidance in designing further targeted studies to determine who is most likely to benefit from this procedure as a first-line treatment,” suggested Vedantham.
Meanwhile, the approach should be reserved as second-line treatment for select patients who have severe limitations of leg function due to DVT and who are not responsive to anticoagulants, advised Vedantham.