SAN DIEGO – Catheter-directed thrombolysis added to standard therapy for deep vein thrombosis reduced the risk of post-thrombotic syndrome by 14.5%, but at an increased cost of bleeding among 209 patients in a randomized, controlled trial.

At 2 years, 55.6% of patients receiving standard treatment with anticoagulation and compression stockings developed post-thrombotic syndrome (PTS), compared with 41.1% receiving catheter-directed thrombolysis (CDT) plus standard therapy (P = .047) in the multicenter CaVenT study.

The number needed to treat to prevent one PTS was seven, Dr. Per Morten Sandset and his colleagues will report in a late-breaking abstract to be presented Dec. 13 at the annual meeting of the American Society of Hematology. About one in four patients is still at risk for developing PTS after adequate treatment with anticoagulation and compression stockings.

The CaVenT (Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis) trial provides much-needed prospective, randomized data on CDT, and is unique in that it focuses on functional rather than surrogate outcomes used in previous trials and case series, Dr. Sandset said at a press briefing in which he discussed the findings.

Still, the study is small and unlikely to change practice or resolve the controversy that has surrounded the use of early fibrinolysis since systemic thrombolytic therapy was introduced decades ago.

"For the first time, we have the evidence to support this type of treatment for centers that have developed this methodology, but I also believe we need further study," said Dr. Sandset, a professor in the division of specialized medicine and surgery at Oslo University in Oslo, Norway.

Briefing moderator Dr. Charles Abrams, associate chief of hematology-oncology at the University of Pennsylvania School of Medicine in Philadelphia, said CaVenT provides the best randomized data to date, but that many clinicians, particularly in the United States, have been hesitant to adopt early fibrinolysis because of the increased risk of a serious bleeding complication.

"This is a tantalizing trial, but I don’t think ... when I’m back at my own institution that the next patient I see with a deep vein thrombosis is probably going to get it," he said.

Both men said results are eagerly awaited from the ongoing phase III, randomized ATTRACT trial evaluating CDT with blood-thinning drugs in 692 patients with proximal DVT. The cohort is three times larger than that of the CaVenT trial, but results from the North American trial are not expected possibly until 2015.

CaVenT randomized 209 patients who presented at 20 hospitals in Norway with their first acute iliofemoral DVT and symptoms present for up to 21 days to CDT with alteplase (Activase) followed by standard treatment or standard treatment alone. In all, 189 patients were evaluable for analysis. Their average age was 51.5 years (range 18-75 years), and 36% were women.

CDT significantly increased the rate of iliofemoral patency at six months from 47.4% with standard therapy to 65.9% (P = .012), Dr. Sandset said.

Importantly, patients who regained iliofemoral patency at six months had significantly less PTS at 2 years than those who experienced insufficient recanalization (36.9% vs. 61.3%, P less than .001). In all, 80 of the 90 patients in the CDT arm had successful lysis.

Bleeding complications were reported in 20 patients in the CDT arm and none in the control arm. Five bleeding events were clinically relevant and three were major, including compartment syndrome of the calf requiring surgery, abdominal wall hematoma requiring transfusion, and an inguinal puncture site hematoma.

No deaths, pulmonary embolisms, strokes or other complications with a permanently reduced outcome were reported, Dr. Sandset said.

"CDT should be considered in patients with acute iliofemoral DVT and no apparent risk of bleeding," he said, adding that the results should be taken into account when guidelines are revised.

One of the problems for clinicians managing patients with DVT is that PTS can vary from simple heaviness in the leg to a constantly swollen leg that can impair the patient’s ability to walk or hold a steady job, Dr. Abrams said.

"Patients with bigger clots and clots higher up in their thigh get more persistent symptoms, but you really can’t predict all that well who will have a bad long-term complication," he said in an interview. "And the downside of this is that the administration of this drug in other trials has led to bleeding complications in 5% of patients, and 2% of that 5% are either strokes or retroperitoneal bleeding."

PTS was identified using the Villalta clinical scale (J Thromb. Haemost. 2009;7:884-8) comprised of five patient-related venous symptoms (pain, cramps, heaviness, paraesthesia and pruritus) and six clinician-rated physical signs (pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia and redness). Using a 4-point scale in which 0 was none and 3 was severe, a total score of less than 5 indicated no PTS, 5-14 was mild/moderate PTS and a score of at least 15 or the presence of venous ulcer was severe PTS.

Dr. Abrams noted that older patients are also at greater risk of a bleeding complication than younger patients, and that clinicians will have to weigh the pros and cons of the current findings in this context with their patients.

Dr. Sandset and Dr. Abrams reported no conflicts of interest.☐

Early Thrombolysis Improves Long-term Outcomes After DVT