Catheter-Directed Thrombolysis Beneficial for Proximal DVT

In the treatment of patients with a high proximal deep vein thrombosis (DVT) and low risk of bleeding, catheter-directed thrombolysis should be considered in addition to conventional antithrombotic treatment, according to data published online December 13, 2011, ahead of print in the Lancet. The findings were released in conjunction with a presentation at the American Society of Hematology 53rd Annual Meeting in San Diego, CA.

For the CaVenT (Catheter-directed Venous Thrombolysis) study, Per Morten Sandset, MD, of Oslo University Hospital (Oslo, Norway), and colleagues looked at 209 patients from 20 Norwegian hospitals with a first-time iliofemoral DVT. The patients were randomized within 21 days of symptom onset to conventional treatment with heparin and warfarin followed by additional warfarin (target INR of 2.0-3.0) with (n = 101) or without (n = 108) adjunctive catheter-directed thrombolysis with alteplase.

Post-Thrombotic Syndrome Risk Reduced 

After 24 months, follow-up was available for 189 patients (90%; 99 control, 90 thombolysis). The incidence of post-thrombotic syndrome, as measured by Villalta score, was lower in the catheter arm at 24 months, and iliofemoral patency was lower in the control group at 6 months (table 1).

Table 1. Short- and Long-term Outcomes

The difference in the incidence of post-thrombotic syndrome corresponds to an absolute risk reduction of 14.4% (95% CI 0.2-27.9), and a number needed to treat of 7 (95% CI 4-502). Twenty bleeding complications occurred related to catheter-directed thrombolysis, including 3 major and 5 clinically relevant bleeds. There were no deaths, pulmonary embolisms, or cerebral hemorrhages related to catheter-directed thrombolysis.

Mean duration of additional thrombolysis was 2.4 days. Overall, catheter-directed thrombolysis enabled complete thrombolysis in 43 patients, and partial lysis (50%-99%) in 37. Ten patients had unsuccessful (< 50%) lysis including 2 technical failures and 2 terminated early due to bleeding complications. 

Functional Outcomes Key 

Dr. Sandset and colleagues observed that determining appropriate outcomes for the trial was problematic, as there was no uniform definition of endpoints in the literature. “Previous DVT studies only looked for recurrent DVT on anticoagulant treatment, which is at best a poor surrogate endpoint,” Dr. Sandset told TCTMD in an e-mail communication. “Rather, we [thought] that functional outcomes should be used. I believe our study is the first to ever use a functional outcome in a DVT study, and my position is that future studies should include functional outcomes and not only recurrent thrombosis.”

Dr. Sandset said he was surprised by the high rate of post-thrombotic syndrome in the study and attributed it to the overall proximal extension of the DVTs. “I believe that the burden of DVT has been neglected, maybe because there has been no treatment to prevent long-term sequelae and because of the long lag time between the acute event and the development of [post-thrombotic syndrome],” he said. “In our study, there was no difference in [post-thrombotic syndrome] after 6 months. After 24 months, the rate was nearly doubled in the control groups as compared to 6 months, but was reduced in the interventional arm.”

Dr. Sandset said his team will continue to follow the patients for 5 years and is interested to see if the differences between the 2 groups will continue to increase. Ultimately, he said, these findings support the “results of numerous case series and uncontrolled studies and therefore significantly expand our evidence base. Our study supports the use of [catheter-directed therapy] in specialized centers with experience with the procedure, but further studies, such as the ongoing ATTRACT study in the United States, are needed, and also studies that implement use of additional devices and procedures.”

More Effective Thrombolysis—But at What Price?

For Mahmood K. Razavi, MD, of the St. Joseph Hospital Heart and Vascular Center (Orange, CA), studying efficacy of additional catheter-directed thrombolysis for patients with DVT is not as important as reducing complication rates.

“We’ve known for a long time, based on our observational practice, that when we lyse patients with DVT and get rid of the clot, the incidence of post-thrombotic syndrome significantly drops,” he told TCTMD in a telephone interview. “The big concern has always been: At what price?”

In addition to being concerned by the high number of bleeding events observed in this study, Dr. Razavi noted that the incidence of post-thrombotic syndrome in the catheter-directed thrombolysis group was higher than he would have liked, attributing this to a “surprisingly low number of stents used in the iliac systems of the patients.”

In the United States, closer to half of patients who undergo DVT thrombolysis have some degree of anatomic obstruction in either the iliac or the common femoral venous system, which requires stenting, Dr. Razavi said. “Having only 15% of the patients stented here was a bit low, and that has to do with a couple of [factors]. One is probably the tolerance for stent [use] in Europe versus the United States. Also, these appear to be experienced stenters, but it seems to me that they may be shy or concerned about stents in the iliac venous system, which they shouldn’t be.”

Although Dr. Razavi cautioned that this dual therapy is not a replacement for standard anticoagulation therapy, he said that additional thrombolysis would be beneficial in patients with proximal DVT, with a reasonable life expectancy, and no contraindications or risk of bleeding.

“These types of studies need to be confirmed before the wider population of patients and physicians buy into it and make an additional treatment standard of care,” he concluded. “We also have to prove that this can be done with a lower complication rate. We need to look at more devices and understand the value of devices in patients with DVT and, most importantly, if we can do single-session treatment of patients with DVT to make this an outpatient procedure.”

Will Help Preserve Limb Function

In an editorial accompanying the study, Lawrence V. Hofmann, MD and William T. Kuo, MD, of Stanford University School of Medicine (Stanford, CA), write that “the incidence of post-thrombotic syndrome in the [catheter-directed thrombolysis] group was still too high—differences in patient selection and procedural technique probably contributed to this finding.”

They also comment on the low incidence of adjunctive venous stenting, noting that “underlying anatomic venous stenosis is clearly one of several risk factors for acute DVT and therefore must be addressed.”

“[These] pivotal trial data will help to preserve limb function in many patients with DVT by reducing the risk of incurable and debilitating post-thrombotic syndrome,” they concluded. “Their trial thereby serves as a powerful motivation to undertake [catheter-directed thrombolysis] for symptomatic acute lower extremity DVT.”

Study Details

Baseline demographic characteristics were similar between the 2 arms. The mean age was 51.5 years and 37% of the patients were female. Mean duration of symptoms was 6.6 days.

By catheter (Uni*Fuse Infusion Catheter, Angiodynamics, Latham, NY), the researchers injected up to 20 mg of alteplase once hourly for up to 4 days. Unfractionated heparin was given simultaneously as a continuous intravenous infusion and the dose was adjusted to keep activated partial thromboplastin time at 1.2-1.7 times higher than the upper normal limit.

 

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Sources:
1. Enden T, Haig Y, Kløw N-E, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): A randomized controlled trial. Lancet. 2011;Epub ahead of print.

2. Hofmann LV, Kuo WT. Catheter-directed thrombolysis for acute DVT. Lancet. 2011;Epub ahead of print.

 

 

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