Catheter-Directed Thrombolysis in Iliofemoral DVT Reduces Risk of Postthrombotic Syndrome

December 13, 2011

December 13, 2011 (San Diego, California) — Catheter-directed thrombolysis significantly reduced the risk of postthrombotic syndrome (PTS) at 24 months compared with standard therapy in patients with deep vein thrombosis (DVT), according to the results of a new study [1]. The addition of thrombolysis also increased venous patency after six months but was associated with an increased risk of bleeding, including three major and five clinically relevant nonmajor bleeding events.

"Current guidelines recommend use of anticoagulant therapy, which is really to stop the growth of the thrombus, but it doesn't dissolve the clot," senior investigator Dr Per Morten Sandset (University of Oslo, Norway) told the media during a press conference announcing the results."This means that a great number of patients will develop residual vein thrombosis after treatment. Most of the patients will also have damage to the valves, and this over time, probably years, will lead to postthrombotic syndrome, which is characterized by pain, swelling of the leg, cramping, sometimes eczema, and also in some severe cases venous ulcers."

To heartwire , Sandset said that acute DVT of the lower limbs occurs in approximately one person per 1000 individuals per year and is associated with significant morbidity, meaning there are approximately 250 000 to 300 000 affected individuals per year in the US. Treatment with anticoagulation usually involves low-molecular-weight heparin for five to 10 days followed by warfarin for a minimum of three months, although some high-risk patients might receive lifelong anticoagulation. Still, even with adequate anticoagulation and compression stockings for acute proximal DVT, approximately one in four patients are at risk for developing PTS.

The results of the study, known as CAVENT, were presented during the late-breaking clinical-trials session at the American Society of Hematology 2011 Annual Meeting by lead investigator Dr Tone Rønnaug Enden (University of Oslo) and published today in the Lancet.

Around Since the 1990s

Systemic thrombolysis with intravenous streptokinase in the setting of acute DVT has been tested in the past, and while it reduced the risk of PTS, it was associated with significant bleeding complications. In contrast, catheter-directed thrombolysis, which has been used since the 1990s, is a treatment where physicians advance the catheter into the affected vein and through the thrombotic segment. Through multiple side holes in the catheter, alteplase, at a significantly reduced dose, is delivered directly into the clot.

In CAVENT, an open-label study that included 209 patients with a first-time iliofemoral DVT, investigators randomized 108 patients to placebo and 101 patients to catheter-directed thrombolysis within 21 days from symptom onset. After 24 months, 37 patients treated with catheter-directed thrombolysis in addition to anticoagulation developed PTS, compared with 55 patients in the anticoagulation-only control arm (41.1% vs 55.6%; p=0.047). When investigators performed an intention-to-treat analysis, the absolute reduction in PTS events increased from 14.5% to 17.0%. At six months, iliofemoral patency was observed in 58 patients treated with thrombolysis compared with 45 patients in the control arm (65.9% vs 47.4%; p=0.012).

The number-needed-to-treat to reduce one PTS event with catheter-directed thrombolysis was seven, report investigators. The benefits of treatment, however, were offset with an increased risk of bleeding. Overall, 20 patients treated with thrombolysis had a bleeding event, including three major and five clinically relevant nonmajor bleeds. There were no deaths, pulmonary embolisms, or cerebral hemorrhages related to thrombolysis.

Sandset said that of the three major bleeding events, two were the result of the procedure, including one that resulted from the puncture site at the popliteal vein. He noted that the study was conducted in four medical centers in Norway and not all physicians were familiar with the therapy. As a result, the bleeding events are slightly higher than he expects them to be when these physicians gain more clinical experience. One of the strengths of the study, he added, was that the primary end point of CAVENT was a functional-outcome measure and that the study included patients at higher risk for PTS given the location of the DVT.

"If you have trained personnel, radiologists that can do the procedure, and you have a patient with extensive thrombosis, in the upper thigh and up into the iliac veins, and a low risk of bleeding, then my recommendation is that these patients also receive catheter-directed thrombolysis," Sandset told heartwire . "We're taking this approach in my hospital, and in Norway as a whole, to recommend this therapy to patients. If the patient doesn't have thrombosis into the upper thigh, we would opt for conventional anticoagulant therapy, either with warfarin or with one of the new anticoagulants."

Speaking during the late-breaking clinical-trials session, Enden agreed, saying the treatment should be considered in patients with acute iliofemoral DVT and no apparent risk of bleeding. Enden said the results of CAVENT should be taken into account when the clinical guidelines are revised.

Study Will Help Preserve Limb Function

In an editorial accompanying the study [2], Drs Lawrence Hoffman and William Kuo (Stanford University School of Medicine, CA) state that catheter-directed thrombolysis has been around for 20 years but the lack of data supporting its benefit and safety has prevented the therapy from taking off. Data from CAVENT, they state, "will help to preserve limb function in many patients with DVT by reducing the risk of incurable and debilitating postthrombotic syndrome."

In addressing the CAVENT study specifically, they point out that 55% of patients in the control arm developed PTS, a number that is too high. To heartwire , Sandset agreed that the incidence of PTS at two years is high but noted the study included patients with extensive thrombosis in the upper thigh and into the iliac veins. The editorialists suggest that iliofemoral stenting following catheter-directed thrombolysis, a practice widely used in the US, might reduce the high rate of PTS. In CAVENT, 23 patients received angioplasty and 15 received venous stenting.

The editorialists also suggest that catheter-directed treatment be performed for one to 1.5 days and should not exceed two days, because a clot that doesn't dissolve within this time frame is likely chronic in nature rather than acute and is unlikely to respond to thrombolysis.

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