Efficacy and safety of home treatment versus in hospital treatment with LMWH in patients with non-massive pulmonary embolism

Acute pulmonary embolism (PE) continues to cause morbidity and mortality and
contributes to up to 200.000 deaths annually in the United States.
Intravenous unfractionated heparin (UFH), given as inpatient treatment,
followed by vitamin K antagonists for a period of six months, has been the part
of standard treatment of venous thromboembolism for several years. Several
clinical trials have demonstrated that administration of low molecular weight
heparin (LMWH) once or twice daily is at least as effective as UFH in
preventing recurrent venous thromboembolism (VTE) with comparable safety
regarding the occurrence of major haemorrhages. LMWH's have a number of
advantages over the standard UFH. They can be administered subcutaneously, have
a more predictable anticoagulant response, which renders laboratory control
unnecessary, and make home treatment in patients with VTE potentially feasible.
The results of randomised studies have demonstrated that LMWH is also as
effective as UFH in the treatment of patients with symptomatic acute
non-massive PE.
Among patients with PE, there is a group of patients, which is at low risk for
adverse events and thus may be potentially amenable to outpatient management.
Once this low risk group is identified, a less complex and less
resource-intensive but equally efficacious and safe treatment is warranted,
allowing for earlier discharge or even prevent hospitalisation. Although LWMH
has been widely used for treatment of deep venous thrombosis (DVT) out of
hospital, their use for out of hospital treatment in patients with acute PE has
not been widely studied.
Two prospective cohort studies have been carried out to evaluate the
feasibility of home treatment for acute PE. In the first study, performed in
108 patients, outpatient treatment with LMWH in patients with PE led to
recurrent VTE and major bleeding in 5.6 % and 2.0 % of patients, respectively,
and with rather wide confidence limits around these incidences. Strength of
this study is that a simple triage model to assess eligibility for home
treatment was used. In the second study, a study nurse treated 70 patients at
home. In one patient a recurrent PE occurred (1.4 %) while another patient got
haemoptysis (1.4%). Finally, in a recent study patients presenting with acute
DVT and/or acute PE were randomised to treatment with either Tinzaparin or
Dalteparin once-daily after which vitamin K antagonists (VKA) was continued for
a period of at least three months on an outpatient basis. In this study a
straightforward triage protocol was used to exclude patients with a too high
risk for outpatient treatment. Of the 505 patients randomised only 90 had acute
PE. The composite endpoint of recurrent VTE and major bleeding was not
different between the two treatment groups, being 4.4 % and 5.9 % in the
Dalteparin and Tinzaparin group respectively (p=0.44). Among the PE patients,
only 2 had a recurrent VTE event (1 DVT, 1 PE) while major haemorrhage did not
occur.

In conclusion, while evidence is accumulating that initial home treatment of
patients with acute PE may be feasible and safe, no study has conclusively
demonstrated effective and safe out of hospital treatment in patients with
acute PE. Given this limited evidence, clinicians remain reluctant to routinely
treat patients with non-massive pulmonary embolism at home with LMWH and as a
result, nearly all patients presenting with acute PE still receive initial
treatment at the hospital.

1. To evaluate the efficacy and safety of out of hospital treatment with LMWH
and Vitamin K antagonists in consecutive patients with objectively proven acute
non-massive pulmonary embolism
2. To perform a health economics evaluation in all patients
3. To perform a quality of life evaluation in all patients.

Triage based cohort follow-up study in patients with acute PE treated out of
hospital

Benefit: Patient satisfaction may be higher in home treatment.

Risk: late complications of PE or bleeding can not managed as quick and
effective in a home setting as in a hospital setting