3. Background
The use of both chemical and mechanical modes of VTE prophylaxis
are standard practice in hospitals today for both medical and surgical
patients…Why?
The incidence of DVT without prophylaxis:
In medical patients: 10-20%
In surgical patients: 40-60%
4. Background
Current CHEST guidelines
recommend using prophylaxis
in patients at increased risk of
thrombosis
However, there is no conclusive evidence that prophylaxis
results in decreased overall mortality in medical patients
5. Objective
“ To evaluate the effect of pharmacologic
thromboprophylaxis on the rate of death
from any cause in acutely ill medical
patients
6. Design
International
No U.S. sites
Funding and study drug Multicenter
supplied by Sanofi Randomized
(manufacturer of Lovenox®)
Double-blind
Placebo-controlled
Parallel-group
7. Design Intervention
Enoxaparin
40 mg SQ injection (0.9% Saline)
for 6 – 14 days
plus
Graduated Compression Stockings
Knee-high (15 mmHg to 10 mmHg)
8. Design Intervention
The study drug was discontinued in the following cases:
“Intercurrent illness” or adverse event
CrCl < 30 ml/min
Plt < 50,000/mm3
Definite VTE requiring treatment
HIT
9. Design Subjects
Age 40+
Hospitalized within the last 48 hours
Anticipated hospital stay of at least 6 days
At least one of the following conditions on admission:
− Acute decompensated heart failure
− Active cancer
− Severe systemic infection plus at least one of the following:
∙ Chronic pulmonary disease
∙ Obesity (BMI 30+)
∙ H/o VTE
∙ Age 60
At least one of the following health status scores at randomization:
− American Society of Anesthesiologist health status score of ≤ 3
− Eastern Cooperative Oncology Group performance status score of ≤ 2
10. Outcomes
Primary
EFFICACY
1) All-cause mortality at day 30
Secondary
2) All-cause mortality at day 14 and day 90
3) Cardiopulmonary death at days 14, 30, and 90
4) Sudden death or fatal PE at days 14, 30, and 90
Primary
1) “Major hemorrhage” during treatment
SAFETY
Secondary
2) Clinically relevant nonmajor bleeding during treatment
3) Minor bleeding during treatment
4) Various measures of ADEs
11. Statistics
Assuming a 7% rate of death in the placebo group
Assuming 5% lost to follow-up
90% power to detect a 25% relative risk reduction
Requires 8300 subjects
14. Outcomes
No significant
differences between the
two study groups
Over half of the subjects
were admitted for a
severe systemic
infection
No break-down of high-
vs. low-risk patients
No mention of patients’
use of HRT
15. Outcomes
No significant differences
between the two study groups for
any of the efficacy measures
Power was not met
The event rate in both groups (4.8-
4.9%) was lower than expected
(7%)
14-day mortality from sudden
death or pulmonary embolism
approaches significance
16. Outcomes
Significantly increased risk of any bleed in the enoxaparin group
Risk of major bleeding approaches significance
17. Conclusions
Still no solid data to show pharmacologic VTE prophylaxis in medical
patients is associated with reduced mortality
Results from this trial may have been affected by:
− Use of GCS on all patients
− No stratification of high- vs. low-risk patients
− 30-day mortality may be too far removed from intervention
− May not reduce overall mortality, but may reduce mortality from
pulmonary emboli
