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Thrombolytic therapy for pulmonary embolism. BACKGROUND: Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may 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 haemorrhage. This is the fourth update of the Cochrane review first published in 2006. OBJECTIVES: To assess the effects of thrombolytic therapy for acute pulmonary embolism. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS: We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.

Thrombolytic therapy for pulmonary embolism. 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 may 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 haemorrhage. This is the third update of the Cochrane review first published in 2006. OBJECTIVES: To assess the effects of thrombolytic therapy for acute pulmonary embolism. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 April 2018. We undertook reference checking to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for 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 review authors (JY, QH) assessed the eligibility and quality of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with 95% confidence interval (CI) or the mean difference (MD) with 95% CI. We assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: We identified no new studies for inclusion in this 2018 update. We included in the review 18 trials with a total of 2197 participants. We were not able to include one study in the meta-analysis because it provided no data that we could extract. Most of the studies carried a high risk of bias because of high or unclear risk related 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 (OR 0.57, 95% CI 0.37 to 0.87, 2167 participants, P = 0.01, low-quality evidence) and recurrence of PE (OR 0.51, 95% CI 0.29 to 0.89, 1898 participants, P = 0.02, low-quality evidence). Effects on mortality weakened when we excluded from analysis four studies at high risk of bias (OR 0.66, 95% CI 0.42 to 1.06, 2054 participants, P = 0.08). The incidence of major and minor haemorrhagic events was higher in the thrombolytics group than in the control group (OR 2.90, 95% CI 1.95 to 4.31, 1897 participants, P < 0.001, low-quality evidence; OR 3.09, 95% CI 1.58 to 6.06, 1553 participants, P = 0.001, very low-quality evidence, respectively). We downgraded the quality of the evidence to low or very low because of design limitations, potential influence of pharmaceutical companies, and small sample sizes. Length of hospital stay (mean difference (MD) -0.89, 95% CI -3.13 to 1.34) and quality of life were similar between the two treatment groups. 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 the small number of participants involved warrant caution when results are interpreted. Similarily, fewer participants from the thrombolytics group required escalation of treatment. None of the included studies reported on post-thrombotic syndrome or compared the costs of different treatments. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that thrombolytics reduce death following acute pulmonary embolism compared with heparin. The included studies used a variety of thrombolytic drugs. Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause major and minor haemorrhagic events and stroke. More high-quality, blinded randomised controlled trials assessing safety and cost-effectiveness of therapies for pulmonary embolism are required.

Thrombolytic therapy for pulmonary embolism. BACKGROUND: 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. OBJECTIVES: To assess the effects of thrombolytic therapy in patients with acute pulmonary embolism. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two authors (BD and QH) assessed the eligibility and quality of trials and extracted data. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.