Clara Kim
Sept. 19, 1997

EBM Conference

Use of low-molecular weight for the treatment of acute symptomatic pulmonary embolism.

Clinical Scenario: 50 y.o. WM from California with pulmonary embolus documented by a high probability V/Q scan. He does notwant to be hospitalized as he has a return flight back home on the following day and inquires about other options.

Clinical Bottom Lines:
1. Treatment of acute pulmonary embolw with low-molecular weight heparin did not show a statistically significant difference when compared with unfractionated hepadn with regards to a combined outcome event, defined as death, recurrent thromboembolism, or major bleeding. This end point was assessed in the first eight days of treatment and during days 9-90 of therapy.
2. Of the 612 patients enrolled in this study, 518 patients were successfully studied to evaluate the change from day 1 to day 8 in the extent of scintigraphically detectable pulmonary vascular obstruction, expressed as a percentage. From day 1 to day 8, the decrease in pulmonary vascular obstruction was not statistically significant between treatment regimens.

Evidence: A multicentered, randomized, unblinded trial of 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular weight heparin (tinzaparin) given once daily
in a fixed dose, or adjusted IV unfractionate2 heparin.

Table 4 OUTCOME EVENTS ACCORDING TO TREATMENT
GROUP

Comments.
1. Unblinded, randomized clinical trial with biases minimized by having all suspected recurrences of venous thromboembolism confirmed by objective tests and all critical events assessed by an independent adjudication committee.
2. One of the first studies in the last two decades to address the use of low molecular weight heparin in acute pulmonary embolus, previously listed as one of the exclusion criteria.
3. Of the 612 patients included in this study, 201 assigned to unfractionated heparin and 222 assigned to low-molecular weight heparin received therapeutic doses of unfractionated heparin for 24 hours or less before randomization. The remaining 189 patients did not receive any unfractionated heparin prior to the start of this study. The results addressing these differences in the
patients were not included in this study.
4. Although the cost of low-molecular weight heparin is greater than IV heparin, this cost analysis does not take into account the added costs from laboratory monitoring, daily hospital costs, inconvenience/hazards of intravenous lines balanced against patient preferences.
5. Based on the inclusion criteria and the base-line characteristics of the study patients, one can argue in defense of its generalizability to one's own clinic population.
6. The low event rate in the overall study population reduced the statistical power of the study to detect a significant difference between treatment groups. Had the trend favoring low-molecular weight heparin continued, almost 10,000 patients would have been required for the study to show a statistically significant difference.
7. Future studies comparing treatment of acute pulmonary embolism with low-molecular weight heparin vs. coumadin alone would be enlightening as if still found to be as safe and effective, one can truly take advantage of the benefit of less stringent laboratory monitoring. In addition, more long-term follow-up may reveal new information.

Reference: Simonneau et al. A Comparison of Low-Molecular Weight Heparin with Unfractionated Heparin for Acute PulmonaryEmbolism.