NICE, FRANCE — Now that safe and effective thrombolytic agents are available for short-term treatment of venous disease, Patrick Mismetti, M.D., has two questions he would like to see answered.
The first is how long to treat venous disease in high-risk patients. The second is, how can clinicians identify those high-risk patients who need long-term preventive therapy?
“We have to evaluate optimal duration of treatment, because there is a place between 6 months and indefinitely,” Dr. Mismetti said at the annual meeting of Cardiovascular and Interventional Radiological Society of Europe. He also called for an epidemiological study to identify patients at high risk of pulmonary embolism.
Physicians need to be able to individualize treatment, balancing the risk of disease recurrence against the risk of bleeding, according to Dr. Mismetti of the Thrombosis Research Group in Saint-Etienne, France.
“We have to try to identify patients at high risk of deep venous disease advancing in order to be aggressive in these patients and to use moderate treatment in other patients,” he said in an interview.
For short-term treatment, he told meeting attendees that low-molecular weight heparin or fondaparinux is preferred. Both are effective and as safe as unfractionated heparin in most patients. Although it is more difficult to administer, he said, unfractionated heparin should be used in patients at risk of major bleeding or severe renal insufficiency.
Long-term treatment reduced recurrences of venous disease in several studies cited by Dr. Mismetti. In one trial, comparing 1 month of therapy after a first episode with 3 months, the rate of recurrence at 1 year fell from 11.4% to 6.4% with the longer treatment (Thromb. Haemost. 1995:74:605–11).
In another study, comparing 1.5 months and 6 months of treatment, the recurrence rates at 2 years were 18.1% and 9.5%, respectively (N. Engl. J. Med. 1995:332:1661–5).
“In both cases, longer duration was associated with significant decrease in deep venous disease recurrences,” Dr. Mismetti said. “However, in certain circumstances, this short treatment of 3 months is not sufficient. We know people who need more treatment.”
For patients who have had a second episode, he cited a study comparing 6 months of treatment to indefinite therapy. Recurrences fell from 20.7% to 2.6% at 4 years with the longer treatment. Risk of major bleeding increased, however, from 2.7% to 8.6% (N. Engl. J. Med. 1997; 336:393–8).
Another placebo-controlled trial was stopped in patients with ideopathic venous disease, he added, because of the high rate of recurrence in patients who did not receive long-term treatment: 27.4% vs. 1.3% (N. Engl. J. Med. 1999;340:901–7).
Although 12 months is now recommended for some patients with idiopathic disease or a second episode, Dr. Mismetti questioned whether that was enough for those at high risk.
Use of a vena cava filter is another issue that needs further study, according to Dr. Mismetti. He was an investigator in the PREPIC (Prévention du Risque d'Embolie Pulmonaire par Interruption Cave) trial, which this summer reported filters reduced risk of pulmonary embolism but increased risk of deep venous thrombosis (Circulation 2005;112:416–22).
Studies are needed to identify the risk factors for recurrence of pulmonary embolism, he said, adding that the group hopes to start a second clinical trial next year.
Scott O. Trerotola, M.D., chair of the meeting session on venous disease, questioned why Dr. Mismetti did not support use of catheter-directed thrombolysis. Dr. Trerotola, of the University of Pennsylvania in Philadelphia, said a randomized study has shown “dramatic improvement” with the technique (Eur. J. Vasc. Endovasc. Surg. 2002;24:209–14).
“I have to present evidence-based medicine, and I try to do it,” Dr. Mismetti replied. “But we have some little experience with this technique, and the weight of deep venous disease recurrence is very high in our small clinical experience.”
“Clearly, for us in the DVT lysis community, the challenge is there to do these trials,” said Dr. Tretorola, noting that several clinical studies are underway.
In an interview, he added that a challenge to validating deep vein thrombolysis is that it works best in clots that are 7–10 days old. Given that many patients are now sent home with low-molecular weight heparin, he said, interventional radiologists often are not called until 2 and 3 weeks later in difficult cases.
“We used to have the opportunity to capture these patients while they were in the hospital and offer treatment for DVT,” he said. “Now we don't, because they're out.”