Drugs to dissolve a blood clot lodged in the lungs (pulmonary embolism)

Dong BR, Hao Q, Yue J, Wu T, Liu GJ

Published Online:

July 8, 2009

A blood clot that lodges in the main artery of the lungs (pulmonary embolism) strains the right side of the heart, affects blood circulation and can be fatal. Patients are also at risk of new blood clots forming (recurrence). With large blood clots (massive pulmonary embolism), restoring blood flow is urgently required. Heparin thins the blood but newer drugs that actively break up the clots (thrombolytics) may act more quickly and be more effective. These newer drugs include streptokinase, urokinase and recombinant tissue-type plasminogen activator. The major complication of treatment is bleeding. The review authors searched the literature and were able to combine data from eight randomized controlled clinical trials. The trials involved 679 adult patients who were in a stable condition and randomly assigned to a thrombolytic agent or heparin. Thrombolytics did not show any benefit over heparin in terms of deaths and recurrence of blood clots. Limited information from only three of the trials showed that they were better at improving blood flow through the lungs. Major bleeding events were similar with both therapies.

The evidence is quite weak and more double-blind trials are needed to show if there is a true benefit of thrombolytic therapy for pulmonary embolism.

Abstract (click to read)

Background:

Thrombolytic therapy is usually reserved for patients with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and might reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhages. This is an update of a Cochrane review first published in 2006.

Objectives:

To assess the effectiveness and safety of thrombolytic therapy in patients with acute PE.

Search strategy:

For this update the Cochrane Peripheral Vascular Diseases Review Group searched their Specialised Register (last searched April 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched Issue 2, 2009). We also searched individual trial collections and private databases, along with bibliographies of relevant articles. Relevant medical journals were handsearched.

Selection criteria:

Randomised controlled trials (RCTs) that compared thrombolytic therapy with placebo or heparin or surgical intervention in patients with acute PE. We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug.

Data collection and analysis:

Two authors (DB and WQ) assessed the eligibility and quality of trials and extracted data.

Main results:

We included eight trials, with a total of 679 patients, in this review. Results between thrombolytics compared with heparin alone or placebo and heparin were similar in terms of:
a) death rate: odds ratio (OR) 0.89; 95% confidence interval (CI) 0.45 to 1.78;
b) recurrence of pulmonary embolism: OR 0.63; 95% CI 0.33 to 1.20;
c) major haemorrhagic events: OR 1.61; 95% CI 0.91 to 2.86;
d) minor haemorrhagic events: OR 1.98; 95% CI 0.68 to 5.75.

We found no trials comparing thrombolytic therapy to surgical intervention.

Using recombinant tissue-type plasminogen activator (rt-PA) and heparin together compared to heparin alone appeared to reduce the need for further treatment for in-hospital events (OR 0.35; 95% CI 0.17 to 0.71).

Thrombolytics improved haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment and echocardiograms to a greater extent than heparin alone.

Authors' conclusions:

Based on the limited evidence found we cannot conclude whether thrombolytic therapy is better than heparin for pulmonary embolism. More double-blind RCTs, with subgroup analysis of patients presenting with haemodynamically stable acute pulmonary embolism compared to those patients with a haemodynamic unstable condition, are required.

This record should be cited as:

Dong BR, Hao Q, Yue J, Wu T, Liu GJ. Thrombolytic therapy for pulmonary embolism. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004437. DOI: 10.1002/14651858.CD004437.pub3

Assessed as up to date:

April 21, 2009

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Primary Review Group:

Peripheral Vascular Diseases Group

Health topics:

Heart & circulation > Pulmonary embolism > Treatment: medical approaches

Heart & circulation > Pulmonary embolism > Treatment: surgery

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Drugs to dissolve a blood clot lodged in the lungs (pulmonary embolism)

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