Patient: WF in her mid-40's with 3 week history of worsening right lower
extremity edema and chronic shortness of breath presented to ED and
underwent bilateral lower extremity dopplers. This demonstrated bilateral
DVTs, including one large, unilateral, above-the-knee clot. The patient
subsequently underwent a chest CT which showed a unilateral saddle pulmonary
embolus. After returning from her CT scan, the patient became acutely
hypotensive.

Question: Are IVC filters in combination with thrombolytics prognostically
favorable compared to thrombolytics alone in the treatment of patients with
DVT?

Article: Temporary Vena Cava Filters and Ultrahigh Streptokinase
Thrombolysis Therapy: A Clinical Study. 2000. Lorch, et al. Cardiovascular
and Interventional Radiology. 23: 273-278.

Description of Study:
1. Materials and Methods
· Retrospective, observational study
· Patient population: 45 consecutive patients age 38.5 +/- 14.8 years
(age range: 17.6 to 60.1 years) with iliac or iliocaval thrombosis not older
than 14 days. No contraindications to thrombolysis existed.
· Before thrombolysis and filter implantation and after treatment, all
patients underwent phlebography +/- phlebo-CT. Doppler ultrasound done
daily during thrombolytic treatment to monitor progression of thrombolysis.
Radiological studies interpreted by same radiologists.
· 4 types of temporary vena cava filters were used.
· Thrombolysis therapy was started immediately after filter insertion.
Patients premedicated with Clemastine (Tavist Ò), Ranitidine, and
Methylprednisolone.
· The maximum duration of thrombolysis was 5 days but could be stopped
earlier if complete recanalization of all venous levels above the calf veins
was achieved or if adverse side effects occurred.
2. Results
· Average duration of thrombolysis therapy was 3.7 +/- 0.9 days.
· Effects of thrombolysis therapy
Complete thrombolysis Thrombolysis success > 50% Thrombolysis success
< 50% No success or thrombus progression
26 patients (58%) 10 patients (22%) 5 patients (11%) 2
patients (4%)
    *Therapy success was not adequately assessed in 2 patients (4%).
· Complications - Twelve patients (27%) suffered from complications
from thrombolysis therapy including hematuria (n=4), fever (n=2), allergic
reaction to streptokinase (n=1), bleeding complications not related to the
puncture site (n=5), and bleeding at the puncture site (n=9).
Eleven patients (24%) suffered complications from the vena cava filter
including dislocation/bending, access issues (infection, thrombosis),
thrombus in filter, and procedural errors. One patient who underwent
filter placement and thrombolytic therapy died from a fatal PE. Post-mortem
exam reveals bilateral fresh emboli and disappearance of a previously
diagnosed pelvic vein clot. The filter was dislocated and folded back. It
remained unclear whether the dislocation was a primary or secondary event,
perhaps caused by resuscitation measures.
· Conclusion: Fatal PE as a complication of thrombolytics of pelvic or
caval thrombosis can not be safely prevented by the temporary vena cava
filter.

Analysis of Study:
1. Are the results valid?
A. Was the sample of patients representative? Maybe
- The only clear exclusion criteria was any patient was
contraindications to receiving thrombolytics. Otherwise, the patients were
chosen in consecutive manner.
- However, the study does not clearly define the sample with regard to
existing comorbid conditions that can ultimately affect the
outcome/complication rate of the treatment in question. Additionally, the
initial sample size is fairly small and is composed of more women than men
(34 vs. 11).
B. Were the patients sufficiently homogenous with respect to prognostic
risk? No
- All patients had iliac or ileocaval DVTs, the researchers do not say
how they determined that clots were no older than 14 days.
- The study does not mention co-morbid conditions that might increase
one's risk for treatment complication (e.g. pre-existing right heart failure
or other cardiac conditions, thrombophilic states, obesity, medications,
baseline functional level, etc).
C. Was the follow-up complete? No
- The study only evaluated acute outcomes of filter placement and
thrombolytics. It fails to follow patients months to years following
therapy, and therefore we do not know whether there were complications
associated with filter removal or even worse, whether PE's recurred at a
later point in time.
- Two patients were removed from the initial, small sample because of
inability to adequately assess therapy success.
D. Were objective and unbiased outcome criteria used? Yes
- The radiographic studies used to evaluate clot progression were
similar for all patients, and the radiologists who interpreted
phlebobgraphy, ultrasound, and CT's were the same.
2. What are the results?
       A. How likely are the outcomes over time? Unsure
- The study focuses on the short term outcome of patients with DVTs
receiving therapeutic intervention, but neglects to comment on long term
recurrence.
B. How precise are the estimates of likelihood? Not applicable...

3. How can I apply the results to patient care?
A. Were the study patients and their management similar to those in my
patient? No
- Similar with respect to age and gender, but again, baseline comorbid
conditions unclear
- Method of diagnosis differs somewhat in that DVTs at UNC usually
determined initially by Doppler rather than phlebography.
- Only a small portion of the sample patients (n=5) had
radiographically proven PE. For our patient with PE and hemodynamic
changes, urgency to treat is obviously greater since clinical decline
portends much poorer prognosis. Similarly, despite the study's conclusion
that fatal PEs as a complication of thrombolytics can not be definitively
prevented by temporary vena cava filters, a filter in the setting of acute
hemodynamic changes and known large clot burden theoretically seems to offer
more protection from PE than thrombolytics alone.
B. Was Follow-up sufficiently long? No
- Given that this study examined the use of temporary filters, it
would be important to know outcome during the time the filter was in place
as well as following removal of the filter (e.g. were there PE events in the
subsequent days while the filter was in place; did the incidence of PE's
significantly increase after filter removal)
C. Can I use the results in the management of patients in my practice?
Possibly

Comments: IVC filters have not been clinically investigated for the
management of massive PE, in particular those with cardiopulmonary
instability manifesting as hypotension, RV dysfunction, or acute respiratory
failure. There remain ethical concerns in subjecting young patients to
lifelong anticoagulation or chronic venous stasis complications with the
placement of an IVC filter as opposed to treatment with thrombolysis when
there are no contraindications.
________________________________________________________________________
Review of Types of Trials

I. Experimental Trial - a study in which the experimenter controls the
conditions; typically an intervention is tested.
a. Quasi-experiment - an experiment in which the investigator is not
able to randomize subjects to conditions because of lack of control over
assignment of subjects or timing of intervention.
b. Controlled Clinical Trial - Study on human subjects, usually with a
clinical condition to evaluate the efficacy of treatment regimen or
behavioral intervention.
1. Randomized - Each study participant is sorted with equal likelihood
to tx or control
a.) Double Blind - Neither patient nor staff know which patient is the
control or intervention group.
b.) Double Blind with crossover design - double blinded trial where
participants are switched from intervention to control in the middle of the
trial and vice versa.
2. Nonrandomized
c. Controlled Community Trials - An experiment in which a unit of
allocation to receive a therapeutic or preventative regimen is an entire
community.
1. Randomized
2. Nonrandomized

         II. Observation Trial - a detailed report from a group of
clinical subjects with related disease
                symptomatology, exposure history, or response to treatment.
a. Case Series - A report on a series of patients with an outcome of
interest. No control group is involved.
b. Cross Sectional Study (aka Prevalence Study) - study that originates
in the present at a single point in time where each person in a study
population is assessed for disease status and exposure. Exposure and
outcome determined simultaneously.
c. Case Control Study (aka Retrospective Study)- study that involves
the identification of person with disease (outcome of interest) and control
patients without the same outcome, and looking back to see if they had the
exposure of interest.
d. Cohort Study (aka Prospective Study) - a study that involves
identification of two groups (cohorts) of patients, one which received the
exposure of interest, and one which did not, and following these cohorts
forward for the outcome of interest.
__________________________________________________________________
References:
Deshpande, K., Hatem, C., Karwa, M., Ulrich, H., Aldrich, T., & Kvetan, V.
2002. The use of inferior vena cava filter as a treatment modality for
massive pulmonary embolism. A case series and review of pathophysiology.
Respiratory Medicine. 96: 984-989.

Lorch, H., Zwaan, M., Siemers, H., Wagner, T., Kagel, C., & Weiss, H. 2000.
Temporary Vena Cava Filters and Ultrahigh Streptokinase Thrombolysis
Therapy: A Clinical Study. Cardiovascular and Interventional Radiology.
23:273-278.