Recommendations
21.

Consider pharmacological systemic thrombolytic therapy for patients with PE and haemodynamic instability (see also recommendation 15).

Relative values of different outcomesAll cause mortality, VTE related mortality and major bleeding were considered the most important outcomes to determine the benefits of the intervention.
Trade off between clinical benefits and harmsThe evidence suggests that treatment with pharmacological thrombolytic therapy may have advantages over anticoagulation in the relative reduction of overall mortality and VTE related mortality. However, pharmacological thrombolytic therapy is associated with the increased risk of harm from major bleeding.

The overall balance of benefit and harm will be dependent on the baseline risk of death from PE compared against the risk of bleeding. Therefore there is an overall clinical benefit for patients with increased risk of death, but lower risk of bleeding. There is overall harm if the treatment is applied to patients with lower risk of death but higher risk of bleeding.

In the evidence reviewed, the baseline risk of mortality i.e. from the heparin alone group in the haemodynamically unstable subgroup is approximately 14% whilst in the haemodynamically stable subgroup it is 4%. Therefore the absolute risk reduction for all cause mortality with thrombolytic therapy is higher in the unstable subgroup (approximately 66 fewer per 1000 patients) than in the stable group (approximately 15 fewer per 1000 patients).

The GDG considered pharmacological thrombolytic therapy to have an overall benefit in the haemodynamically unstable subgroup but not the stable subgroup.
Economic considerationsNo economic evidence was found on this population.

Thrombolytic therapy is likely to increase initial costs of material and length of stay. The overall effectiveness of the interventions is determined by their impact on mortality, the recurrence of PE or DVT, the risk of chronic thromboembolic pulmonary hypertension and the risk of bleeding. As the baseline risks are higher in the haemodynamically unstable population, thrombolytic treatment is likely to be cost-effective for this group.
Quality of evidenceThe quality of evidence for all cause mortality, VTE related mortality and major bleeding was very low due to study limitations, indirectness of evidence and very serious imprecision. Various definitions of severity were used for the studies reviewed, and there were no clear differentiation between patients with haemodynamically stable and unstable PE.

The values for VTE recurrence were not pooled because most of the studies have a very short time of follow up and were poorly reported.

The potential of bias and uncertainty in the clinical evidence led the GDG to make recommendations where treatments should be considered for haemodynamically unstable patients rather than offered. The treatment should be considered by the clinician and patient preference should be taken into account when feasible.
Other considerationsThis recommendation was based on the clinical evidence and supported by GDG opinion, and therefore it is a “consider” recommendation. It will be important to discuss the options with patients when feasible.

The GDG considered the risk of mortality from PE compared to the risk of bleeding as the most important factors in the decision of whether to offer treatment. In haemodynamically unstable patients, there is a higher risk of mortality and the benefit from the reduction of mortality outweighed the risk of bleeding in this group. However within this group there is likely to be heterogeneity and treatment should be considered on a patient to patient basis.

The GDG also considered that there are important limitations in the evidence reviewed:
  • The baseline risk of mortality for the haemodynamically unstable group may be higher, from 15 to 50% based on epidemiological studies and risk registries.
  • The risk of bleeding in current practice may be lower than in studies; the studies used pulmonary angiography to confirm PE which is invasive and could put the patients at higher risk of bleeding.
The evidence available was only for pharmacological therapy and therefore only this has been recommended. Many of the studies were unclear as to whether they had used systemic or catheter-directed pharmacological thrombolytic therapy. As there is a higher risk of bleeding from the puncture site with catheter directed thrombolysis and as it is less widely available, the GDG included the term ‘systemic’ on consensus.

Recommendations for anticoagulation treatment for patients with confirmed PE are detailed in the Pharmacological chapter (Section 7.5 Recommendations and link to evidence)

From: 9, Thrombolytic therapy for PE

Cover of Venous Thromboembolic Diseases
Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing [Internet].
NICE Clinical Guidelines, No. 144.
National Clinical Guideline Centre (UK).
Copyright © 2012, National Clinical Guideline Centre.

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