Geneva, Switzerland - Low-molecular-weight-heparin (LMWH) prophylaxis in nonsurgical patients at increased risk for venous thromboembolism (VTE) should be extended for about a month after hospital discharge, suggests a randomized trial in which the strategy was associated with a significant 44% reduction in risk of VTE events [1]. The benefit came at the cost of a small but significant increase in the risk of bleeding complications, mostly minor ones.

The Extended Clinical Prophylaxis in Acutely Ill Medical Patients (EXCLAIM) trial, conducted primarily in North America and Europe, randomized patients immobilized in the hospital with acute medical conditions who had been put on subcutaneous enoxaparin (Lovenox/Clexane, Sanofi-Aventis) to continue it or receive a placebo after discharge. The preliminary results were presented here this week at the 2007 Congress of the International Society on Thrombosis and Hemostasis.

Dr Samuel Z Goldhaber (Brigham and Women's Hospital, Boston, MA), who wasn't involved in EXCLAIM but was on hand for the study's oral presentation, said it "appears to have been rigorously conducted" and, although it has yet to be subjected to formal peer review, the results are "extremely promising and may in fact be a very major breakthrough."

Although several randomized trials support the use of short-term VTE prophylaxis for patients like those in EXCLAIM, Goldhaber observed for heartwire, extending it beyond the first seven to 10 days "is an unknown clinical area." The risks appear to extend long after that early period, he said.

"We need more extensive information before changing current medical practice," according to Goldhaber. In particular, the extended-prophylaxis regimen's potential for bleeding complications needs further exploration, he said. "Nevertheless, I think individual practitioners should take EXCLAIM into account now when they are making individual patient care decisions at the time of hospital discharge."

Although extended-duration anticoagulant prophylaxis is routine for patients immobilized after major surgery, formal guidelines and even clinical-trial support have been lacking for high-risk medical patients. "That's why EXCLAIM is a landmark study," Dr Victor F Tapson (Duke University Medical Center, Durham, NC), one of the trial's lead investigators, said to heartwire. "In the medically ill, now we have very good data suggesting that prolonged prophylaxis makes sense."

In EXCLAIM, 5101 hospitalized patients with varying levels of immobility—with onset within the previous three days for reasons that included cancer, ischemic stroke, heart failure, respiratory failure, and infections—received subcutaneous enoxaparin 40 mg/day for an average of 10 days on an open-label basis [2]. Most of the patients were then randomized in the double-blind phase to receive either placebo or continued prophylaxis at the same dosage, which continued for a mean of 28 additional days.

The significant reduction in risk of VTE events persisted out to 90 days; the rates for extended prophylaxis and placebo then were 3.0% and 5.2%, respectively (p=0.0015). All-cause mortality at six months didn't differ between the groups (10.1% and 8.9%, respectively; p=0.18).

Tapson said the rates of total, major, and minor bleeding events during the extended-duration prophylaxis phase of the study were low in both groups and that the significant increases with enoxaparin were in line with expectations and didn't appear clinically important. There was one instance of fatal bleeding, an intracranial hemorrhage in the enoxaparin group, he said. But in a trial of this kind and size, "it could have been in either group."

"Nowadays, our culture is changing so that we're discharging sicker, higher-risk patients than we ever did before," Goldhaber observed. Their risk of VTE complications is probably increased after discharge, he speculated, because they are no longer getting encouragement to move around from nurses and physical therapists. Extended-duration prophylaxis may help reduce that risk, he said.