A Cochrane review included 18 trials with a total of 2197 participants. 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.
A systematic review including 8 RCTs with a total of 453 subjects was abstracted in DARE. Follow-up ranged from 3 days to 12 months. In the quantitative synthesis, 7 out of 8 RCTs found no differences in the resolution of the thrombus in both treatment groups after the start of therapy. No statistically significant differences in mortality were observed between patients treated with only heparin and those treated also with some type of thrombolytic drug. There was no difference in the incidence of relapses. Patients receiving thrombolytic therapy showed a 2.5 fold risk of suffering some type of haemorrhage than patients not receiving it (OR 2.6, 95% CI 1.6 to 4.4).
Another systematic review including 9 randomized trials (461 patients) comparing thrombolytic therapy to heparin and 6 RCTs (481 patients) comparing efficacy and safety of one thrombolytic versus another was assessed in DARE. Thrombolytic therapy resulted in more rapid clot resolution, but with 5 to 7 days, both treatments produced similar improvements in pulmonary perfusion. Based on data from a small, randomized study, thrombolysis appears to reduce mortality in patients with shock due to massive pulmonary embolism.