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 21st 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.

Tapson said he has received research funding from Sanofi-Aventis and
has consulted for that company as well as Eisai, which markets
dalteparin (Fragmin), another LMWH indicated for VTE prophylaxis,
and Bayer. Goldhaber said he has received research funding from and
has consulted for Sanofi-Aventis, but not in connection with
EXCLAIM; he also reports having consulted for Eisai, Boehringer-
Ingelheim, GlaxoSmithKline, and Bristol-Myers Squibb.

Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous
thromboembolism prophylaxis in acutely ill medical patients with
recent reduced mobility: The EXCLAIM study. 2007 Congress of the
International Society on Thrombosis and Hemostasis; July 7-13, 2007;
Geneva, Switzerland. Late-breaking clinical trials, abstract O-S-
001.
Hull RD, Schellong SM, Tapson VF, et al. Extended-duration
thromboprophylaxis in acutely ill medical patients with recent
reduced mobility: Methodology for the EXCLAIM study. J Thromb
Thrombolysis 2006; 22:31-38.