Tutorial 1a



Article: A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Acute Pulmonary Embolism

Authors: Simonneau G, Sors H, Charbonnier B, et al

Publication: NEJM 1997;337:663-9

Study: multicenter trial comparing continuous unfractionated heparin with once daily LMWH (tinzaparin) in patients with acute symptomatic PE

Inclusion Criteria: consecutive patients over 18 yrs old with clinical suspicion of PE diagnosed by pulmonary angiography, high prob VQ scan, or indeterminate VQ with DVT confirmed by venography or US

Exclusion Criteria: massive PE requiring thrombolytics or embolectemy; active bleeding; contraindication to anticoagulation; anticoagulation for >24 hrs prior to study entry; life expectancy <3 mo; severe hepatic or renal failure; noncompliance likely; pregnancy

Step 1: Are the results of the study valid?

Step 1a: Was there randomization?

Yes


Step 1b: Was there excessive loss to follow-up?

No


Step 1c: Was there an intention to treat analysis?

Yes


Step 1d: Was the study blinded?

No


Step 1e: Were treatment groups similar other than intervention?

Yes

Step 2: What are the results?

 Outcome

(90 day)

 Unfractionated

Heparin

(N=308)

 LMWH

(N=304)

 ARR  RR  RRR  NNT
 Death  14  12  0.6%  86.8%  13.2%  167

 Recurrent

Thromboembolism

 6  5  0.3%  84.1%  15.9%  323
 Major Bleeding  8  6  0.6%  75.8%  24.2%  159
 Combined Event  22  18  1.2%  82.9%  17.1%  82

* Confidence intervals were not given for the above data. When calculated using the worksheet from the Oxford Center for EBM, the CI's were non significant (the values crossed zero). The above results for ARR, RR, RRR, NNT really have no meaning since the results are not significant but are shown as an exercise in calculating these values.

Step 3: Will the results help in caring for my patients?

Limitations
1. unblinded study but used objective criteria to define outcome event and the data on potential events were reviewed by an independent committee unaware of treatment
2. 69% of patients received therapeutic unfractionated heparin prior to the study drug for a mean duration of 18 hrs (201 patients in the unfractionated heparin group and 222 patients in the LMWH group)
3. follow up was limited to 3 months
4. no comment on length of hospitalization

Conclusion

LMWH is as safe and effective as unfractionated heparin in the treatment of patients with symptomatic PE according to this study. Keep in mind the above limitations of the study design when applying the data to your own patients.