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Three Part Question

In [patients with Acute Pulmonary Embolus after thrombolytic] does [treatment with unfractionated heparin (UFH) or Low Molecular Weight Heparin] reduce [adverse outcomes]?

Clinical Scenario

A 72 year old gentleman is admitted to the Emergency Department Resuscitation suite. He is hypoxic, hypotensive with right ventricular strain on ECG and a CT scan performed showed a large saddle embolus. He is given thrombolytic therapy and you are asked to prescribe ongoing anticoagulation. You wonder if there is any evidence to support the use of a unfractionated heparin infusion as compared to a Low Molecular Weight Heparin to reduce adverse outcomes?

Search Strategy

Ovid MEDLINE(R) 1946 to March Week 4 2017
[exp Pulmonary Embolism/ OR exp Venous Thromboembolism] AND {exp Thrombolytic Therapy/ OR Thrombolysis.mp.] AND [exp unfractionated heparin.mp. OR exp Heparin/] AND [exp Heparin, Low-Molecular-Weight/] LIMIT to Human AND English Language

Search Outcome

Altogether 40 papers were found through Medline, 2 of which were relevant to the three part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ucar et al 2015 Turkey	121 Patients over the age of 18 who had a massive PTE (pulmonary thromboembolism) who have undergone thrombolytic treatment randomised to LMWH (n=60) or UFH (n=61) group.	Randomised controlled parallel group study.	Frequency of Death, Major Haemorrhage, Minor haemorrhage, and any adverse events	The occurrence of any adverse event and each individual type of adverse event (death, major haemorrhage, all haemorrhage, any adverse events) were all lower in the LMWH group compared to UFH group, the differences were not, however, statistically significant with all p-values ≥0.27	This was a single centre study and due to the low rate of occurance of major haemorrhage it lacked the statistical power to give any significant findings and larger trials would be required to confirm results.
Senturk et al. 2015 Turkey	249 patients with acute PE (both massive and submassive) who required thrombolysis were categorized into two groups depending on treatment with Low Molecular Weight Heparin (LMWH) or UFH (Unfractionated Heparin)	Prospective, observational multicenter trial	Difference in 30-day mortality, major and minor haemorrhage between LMWH and UFH grouping.	There was a nonsignificant unadjusted 2-sided P value either major or minor haemorrhage. No significant difference between the LMWH and the UFH group for 30-day mortality (P-value 0.082)	This was an observational study rather then a controlled trial between the two treatment modalities. The patient groupings were not randomised, though a regression analysis was performed for calculating 30-day mortality. The data was collected prospectively, however the study was designed retrospectively.

Comment(s)

There are a surprising lack of studies looking into the treatment post thrombolysis, specifically looking at a head to head comparison between the two most used treatment modalities of LMWH or UFH. There are numerous studies looking into both of these options as initial therapy for pulmonary thromboembolism but few assessing use post thromblytic therapy. Both of the studies showed a slight decrease in adverse events in the LMWH grouping however there was no statistically significant difference shown in either study in adverse effects, including mortality rates, major and minor haemorrhage, between the two treatment modalities following thrombolysis.

Clinical Bottom Line

There has been no statistically significant difference found in adverse outcomes including mortality, major haemorrhage and minor haemorrhage between the use of LMWH or UFH to treat acute pulmonary thromboembolism after trombolytic treatment, therefore local and national guidance should be followed as to which modality is used.

References

1. Ucar, E.Y., Akgun, M., Araz, O. et al. Comparison of LMWH Versus UFH for Hemorrhage and Hospital Mortality in the Treatment of Acute Massive Pulmonary Thromboembolism After Thrombolytic Treatment Lung 2015; 121-127:
2. Senturk, A., Ucar, E., Berk, S. et al. Should Low-Molecular-Weight Heparin be Preferred Over Unfractionated Heparin After Thrombolysis for Severity Pulmonary Embolism? Clinical and Applied Thrombosis/Hemostasis 2015; 395-399: