Qiukui Hao, Bi Rong Dong, Jirong Yue, Taixiang Wu, Guan J Liu

Thrombolytic therapy (powerful anticoagulation drugs) 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 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 the second update of the Cochrane review first published in 2006. To assess the effects of thrombolytic therapy in patients with acute pulmonary embolism. For this update the Cochrane Vascular Group searched their Specialised Register (last searched September 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (last searched Issue 8, 2014). We also searched individual trial collections and private databases, along with bibliographies of relevant articles. We handsearched relevant medical journals. Randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo 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. Two authors (BD and QH) assessed the eligibility and quality of trials and extracted data. We identified 18 trials with a total of 2197 participants for inclusion in the review. We were not able to include one study in the meta-analysis because it had no data to extract. Most of the studies carried a high risk of bias because of high or unclear risk relating to randomisation and blinding. Meta-analysis showed that, compared with heparin alone, or heparin plus placebo, thrombolytics plus heparin can reduce the odds of death (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.37 to 0.87, P = 0.02, low quality evidence) and recurrence of PE (OR 0.51; 95% CI 0.29 to 0.89, P = 0.02, low quality evidence). The effects of death weakened when we excluded four studies at high risk of bias from analysis: OR 0.66, 95% CI 0.42 to 1.06, P = 0.08. The incidence of major and minor haemorrhagic events was higher in the thrombolytics group than in the control group, and this difference was statistically significant (OR 2.90, 95% CI 1.95 to 4.31, P < 0.001, low quality evidence; OR 3.09, 95% CI 1.58 to 6.06, P = 0.001, very low quality evidence, respectively). Length of hospital stay (mean difference (MD) -1.35, 95% CI -4.27 to 1.58) and quality of life were similar between the two treatment groups. Stroke was reported in one study and occurred more often in the thrombolytics group than in the control group, although the confidence interval was wide (OR 12.10, 95% CI 1.57 to 93.39). Limited information from a small number of trials indicated that thrombolytics may improve haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, clinical outcomes and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and small number of participants involved warrant caution when interpreting results. Similarily, fewer patients from the thrombolytics group required escalation of treatment. None of the included studies reported on post-thrombotic syndrome or compared the cost of the different treatments. There is low quality evidence that thrombolytics reduce death following acute pulmonary embolism compared with heparin. Furthermore, thrombolytic therapies included in the review were heterogeneous. Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events and stroke. More high quality double blind RCTs assessing safety and cost-effectiveness are required.