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.
BACKGROUND: Standard treatment for deep vein thrombosis (DVT) aims to reduce immediate complications. Use of thrombolytic clot removal strategies (i.e. thrombolysis (clot dissolving drugs), with or without additional endovascular techniques), could reduce the long-term complications of post-thrombotic syndrome (PTS) including pain, swelling, skin discolouration, or venous ulceration in the affected leg. This is the fourth update of a Cochrane Review first published in 2004.
OBJECTIVES: To assess the effects of thrombolytic clot removal strategies and anticoagulation compared to anticoagulation alone for the management of people with acute deep vein thrombosis (DVT) of the lower limb.
SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 21 April 2020. We also checked the references of relevant articles to identify additional studies.
SELECTION CRITERIA: We considered randomised controlled trials (RCTs) examining thrombolysis (with or without adjunctive clot removal strategies) and anticoagulation versus anticoagulation alone for acute DVT.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. We assessed the risk of bias in included trials with the Cochrane 'Risk of bias' tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we calculated the risk ratio (RR) with the corresponding 95% confidence interval (CI). We pooled data using a fixed-effect model, unless we identified heterogeneity, in which case we used a random-effects model. The primary outcomes of interest were clot lysis, bleeding and post thrombotic syndrome.
MAIN RESULTS: Two new studies were added for this update. Therefore, the review now includes a total of 19 RCTs, with 1943 participants. These studies differed with respect to the thrombolytic agent, the doses of the agent and the techniques used to deliver the agent. Systemic, loco-regional and catheter-directed thrombolysis (CDT) strategies were all included. For this update, CDT interventions also included those involving pharmacomechanical thrombolysis. Three of the 19 included studies reported one or more domain at high risk of bias. We combined the results as any (all) thrombolysis interventions compared to standard anticoagulation. Complete clot lysis occurred more frequently in the thrombolysis group at early follow-up (RR 4.75; 95% CI 1.83 to 12.33; 592 participants; eight studies) and at intermediate follow-up (RR 2.42; 95% CI 1.42 to 4.12; 654 participants; seven studies; moderate-certainty evidence). Two studies reported on clot lysis at late follow-up with no clear benefit from thrombolysis seen at this time point (RR 3.25, 95% CI 0.17 to 62.63; two studies). No differences between strategies (e.g. systemic, loco-regional and CDT) were detected by subgroup analysis at any of these time points (tests for subgroup differences: P = 0.41, P = 0.37 and P = 0.06 respectively). Those receiving thrombolysis had increased bleeding complications (6.7% versus 2.2%) (RR 2.45, 95% CI 1.58 to 3.78; 1943 participants, 19 studies; moderate-certainty evidence). No differences between strategies were detected by subgroup analysis (P = 0.25). Up to five years after treatment, slightly fewer cases of PTS occurred in those receiving thrombolysis; 50% compared with 53% in the standard anticoagulation (RR 0.78, 95% CI 0.66 to 0.93; 1393 participants, six studies; moderate-certainty evidence). This was still observed at late follow-up (beyond five years) in two studies (RR 0.56, 95% CI 0.43 to 0.73; 211 participants; moderate-certainty evidence). We used subgroup analysis to investigate if the level of DVT (iliofemoral, femoropopliteal or non-specified) had an effect on the incidence of PTS. No benefit of thrombolysis was seen for either iliofemoral or femoropopliteal DVT (six studies; test for subgroup differences: P = 0.29). Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included four trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion.
AUTHORS' CONCLUSIONS: Complete clot lysis occurred more frequently after thrombolysis (with or without additional clot removal strategies) and PTS incidence was slightly reduced. Bleeding complications also increased with thrombolysis, but this risk has decreased over time with the use of stricter exclusion criteria of studies. Evidence suggests that systemic administration of thrombolytics and CDT have similar effectiveness. Using GRADE, we judged the evidence to be of moderate-certainty, due to many trials having small numbers of participants or events, or both. Future studies are needed to investigate treatment regimes in terms of agent, dose and adjunctive clot removal methods; prioritising patient-important outcomes, including PTS and quality of life, to aid clinical decision making.
AIM: traitement thrombolytique induit rapidement la dissolution du caillot que l'anticoagulation chez les patients présentant une embolie pulmonaire aiguë (PE), mais est associée à un risque accru d'hémorragie. Nous avons examiné les risques et les avantages de la thérapie thrombolytique dans la gestion des patients atteints de PE aiguë.
MÉTHODES ET RÉSULTATS: Nous avons systématiquement examinés études randomisées contrôlées comparant un traitement thrombolytique systémique ainsi que l'anticoagulation par anticoagulation seule chez les patients souffrant d'EP aiguë. Quinze essais impliquant 2057 patients ont été inclus dans notre méta-analyse. En comparaison avec l'héparine, un traitement thrombolytique a été associée à une réduction significative de la mortalité globale (OU; 0,59, IC 95%: 0,36 à 0,96). Cette réduction ne était pas statistiquement significative après exclusion des études, y compris PE à haut risque (OR; 0,64, IC 95%: 0,35 à 1,17). Le traitement thrombolytique a été associée à une réduction significative du critère combiné de décès ou l'escalade de traitement (OR: 0,34, IC 95%: 0,22 à 0,53), la mortalité liée au PE (OR: 0,29; IC 95%: 0,14 à 0,60) et PE récidive (OR: 0,50; IC 95%: 0,27 à 0,94). Hémorragie majeure (OU; 2,91, IC 95%: 1,95 à 4,36) et hémorragies mortelles ou intracrânienne (OR: 3,18, IC à 95%: 1.25 à 8.11) étaient significativement plus fréquents chez les patients recevant la thrombolyse.
CONCLUSIONS: Le traitement thrombolytique réduit la mortalité totale, PE récidive, et la mortalité liées PE chez les patients souffrant d'EP aiguë. La diminution de la mortalité globale est toutefois pas significative chez les patients hémodynamiquement stables avec PE aiguë. Le traitement thrombolytique est associée à une augmentation de l'hémorragie majeure et fatale ou intracrânienne.
IMPORTANCE: Le traitement thrombolytique peut être bénéfique dans le traitement de certains patients souffrant d'embolie pulmonaire. À ce jour, aucune analyse n'a eu la puissance statistique suffisante pour déterminer si la thérapie thrombolytique est associée à une amélioration de la survie, par rapport à l'anticoagulation conventionnelle.
OBJECTIF: Déterminer les avantages de la mortalité et les risques hémorragiques associés à la thérapie thrombolytique par rapport à l'anticoagulation dans l'embolie pulmonaire aiguë, y compris le sous-ensemble de patients hémodynamiquement stables avec dysfonction ventriculaire droite (embolie pulmonaire à risque intermédiaire).
SOURCES DE DONNÉES: PubMed, la Cochrane Library, EMBASE, EBSCO, Web of Science, et les bases de données CINAHL de création à 10 Avril 2014.
SÉLECTION DES ÉTUDES: Les études admissibles ont été randomisés essais cliniques comparant la thérapie thrombolytique vs traitement anticoagulant chez les patients atteints d'une embolie pulmonaire. Seize essais comprenant 2115 individus ont été identifiés. Huit essais comprenant 1775 patients spécifiés inclusion des patients atteints de risque intermédiaire embolie pulmonaire.
EXTRACTION DE DONNÉES ET SYNTHÈSE: Deux auteurs ont extrait indépendamment les données au niveau du procès, y compris nombre de patients, les caractéristiques des patients, la durée du suivi, et les résultats.
LES RÉSULTATS ET MESURES PRINCIPALES: Les principaux résultats étaient la mortalité toutes causes confondues et les saignements majeurs. Les résultats secondaires étaient risque d'embolie récurrente et une hémorragie intracrânienne (ICH). Peto odds ratio (OR) et les estimations associées IC à 95% ont été calculées en utilisant un modèle à effets fixes.
RÉSULTATS: L'utilisation de thrombolytiques était associée à une plus faible mortalité toutes causes confondues (OR, 0,53; IC 95%, 0,32 à 0,88; 2,17% [23/1061] vs 3,89% [41/1054] avec des anticoagulants; nombre nécessaire à traiter [NNT ] = 59) et de plus grands risques de saignements majeurs (OR, 2,73; IC 95%, 1,91 à 3,91; 9,24% [98/1061] vs 3,42% [36/1054], le nombre nécessaire pour nuire [NNH] = 18) et ICH (OR, 4,63; IC 95%, 1,78 à 12,04; 1,46% [15/1024] vs 0,19% [2/1019]; NNH = 78). Le saignement majeur n'a pas augmenté de façon significative chez les patients de 65 ans et plus jeunes (OR, 1,25; IC 95%, 0,50 à 3,14). Thrombolyse a été associée à un risque plus faible de l'embolie pulmonaire récurrente (OR, 0,40; IC 95%, 0,22 à 0,74; 1,17% [12/1024] vs 3,04% [31/1019]; NNT = 54). In-risque intermédiaire des essais d'embolie pulmonaire, la thrombolyse a été associée à une mortalité plus faible (OR, 0,48; IC 95%, 0,25 à 0,92) et plus d'événements hémorragiques majeurs (OR, 3,19; IC à 95%, 2,07 à 4,92).
CONCLUSIONS ET PERTINENCE: Chez les patients présentant une embolie pulmonaire, y compris ceux qui étaient hémodynamiquement stables avec dysfonction ventriculaire droite, la thérapie thrombolytique a été associée à des taux inférieurs de mortalité toutes causes et des risques accrus de saignements majeurs et ICH. Cependant, les résultats peuvent ne pas appliquer aux patients présentant une embolie pulmonaire qui sont hémodynamiquement stable sans dysfonction ventriculaire droite.
BACKGROUND: In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups. METHODS AND RESULTS: An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients. CONCLUSIONS: Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding. CLINICAL TRIAL REGISTRATION URL: www.anzctr.org.au. Unique identifier: ACTRN12611000684921.
CONTEXTE: L'efficacité de la thérapie thrombolytique chez les patients présentant une embolie pulmonaire submassive (PE) reste incertaine. méta-analyses antérieures ont pas séparément rapporté la proportion de patients avec PE submassive.
OBJECTIF: Nous avons évalué l'effet de la thérapie thrombolytique sur la mortalité, PE récurrente, une détérioration clinique nécessitant un traitement escalade et des saignements chez les patients atteints submassive PE.
MÉTHODES: Le MEDLINE, les bases de données Embase et Cochrane Library ont cherché à identifier tous les essais pertinents randomisés contrôlés comparant la thérapie thrombolytique adjuvante avec de l'héparine seule comme traitement initial chez les patients atteints PE submassive aiguë, et rapportés mortalité à 30 jours ou les résultats cliniques à l'hôpital.
RÉSULTATS: Un total de 1510 patients ont été inclus dans cette méta-analyse. Aucune différence significative n'a été apparente dans le critère composite de décès toutes causes confondues ou PE récurrente entre le bras de thérapie thrombolytique adjuvante et le bras de l'héparine seule (3,1% contre 5,4%; RR, 0,64 [0,32 à 1,28]; P = 0,2) . la thérapie thrombolytique adjuvante réduit significativement l'incidence du critère composite de décès toutes causes confondues ou détérioration clinique (3,9% vs 9,4%; RR, 0,44; P <0,001). Il n'y avait aucune association statistiquement significative pour les saignements majeurs quand la thérapie thrombolytique adjuvante a été comparé à la thérapie de l'héparine seule (6,6% vs 1,9%; P = 0,2).
CONCLUSIONS: Cette méta-analyse montre que la thérapie thrombolytique adjuvante ne réduit pas significativement le risque de mortalité ou de PE récurrente chez les patients atteints PE submassive aiguë, mais adjuvant la thérapie thrombolytique empêche la détérioration clinique nécessitant l'escalade du traitement chez les patients atteints PE submassive aiguë. Bleeding évaluation des risques pourrait être l'approche la plus efficace pour améliorer les résultats cliniques et avantages spécifiques au patient.
OBJECTIF: L'objectif de cette revue systématique était d'évaluer l'efficacité et l'innocuité du traitement thrombolytique chez les patients présentant une embolie pulmonaire submassive (PE).
MÉTHODES: Une recherche électronique a été effectuée sur la base des bases de données de MEDLINE, Embase, Science Citation Index (SCI), et la Bibliothèque Cochrane. Nous avons inclus des essais prospectifs, randomisés et cliniques en thrombolyse avec l'héparine seule chez les adultes qui ont eu des signes de dysfonction ventriculaire droite et normotension. Les principaux critères d'évaluation comprennent la mortalité, PE récurrente, et le risque de saignement. Le risque relatif (RR) et les intervalles de confiance pertinents 95% ont été déterminées par la variable dichotomique.
RÉSULTATS: Seulement sept études impliquant 594 patients répondaient aux critères d'inclusion pour un examen plus approfondi. L'effet cumulatif de la thrombolyse, par rapport à l'héparine par voie intraveineuse, a démontré aucune différence statistiquement significative de la mortalité (2,7% contre 4,3%; RR = 0,64 [0,29 à 1,40]; P = 0,27) ou PE récurrent (2% contre 5%; RR = 0,44 [0,19 à 1,05], p = 0,06). Le traitement thrombolytique n'a pas augmenté d'hémorragie majeure par rapport à l'héparine par voie intraveineuse (4,5% versus 3,3%; RR = 1,16 [0,51 à 2,60]; P = 0,73), mais il a été associé à une hémorragie mineure a augmenté (41% contre 9%; RR = 3,91 [1,46 à 10,48], p = 0,007).
CONCLUSION: En comparaison avec l'héparine seule, ni la mortalité ni récurrente PE est réduit par thrombolyse chez les patients avec PE submassive, et il ne révèle pas un risque accru de saignement majeur. En outre, la thrombolyse produit également le risque accru de saignement mineur; cependant, aucune preuve suffisante vérifie le bénéfice thrombolytique dans cette revue, parce que le nombre de patients inclus dans les essais est limité. Par conséquent, un grand essai clinique en double aveugle est nécessaire pour prouver les résultats de cette méta-analyse.
CONTEXTE: Les patients atteints de thrombose veineuse profonde (TVP) aiguës peuvent sans risque être traités en ambulatoire. Toutefois, le rôle du traitement ambulatoire des patients diagnostiqués avec une embolie pulmonaire (EP) est controversée. Nous avons cherché à déterminer l'innocuité de prise en charge ambulatoire des patients ayant une embolie pulmonaire.
MATÉRIEL ET MÉTHODES: Une stratégie de recherche systématique de la littérature a été réalisée en utilisant Medline, Embase, le registre Cochrane des essais contrôlés et tous les commentaires EBM. Proportions communs pour les différents résultats ont été calculés.
Résultats: Un total de 1258 patients ont été inclus dans la revue systématique. Le taux de thromboembolie veineuse (TEV) récurrente chez les patients atteints PE gérée en ambulatoire était de 1,47% (IC 95%: 0,47 à 3,0%; I (2): 65,4%) au cours de la période de suivi de trois mois. Le taux d'accidents mortels PE était de 0,47% (IC 95%: 0,16 à 1,0%; I (2): 0%). Les taux de saignements majeurs et d'hémorragies intracrâniennes mortelles étaient de 0,81% (IC 95%: 0,37 à 1,42%; I (2): 0%) et 0,29% (IC 95%: 0,06 au 0,68%; I (2): 0% ), respectivement. Le taux global de mortalité trois mois était de 1,58% (IC 95%: 0,71 à 2,80%; I (2): 45%). Les taux d'événements étaient similaires, s'ils emploient des modèles de stratification du risque plutôt que d'utiliser gestalt clinique pour sélectionner les patients appropriés pour la gestion des soins ambulatoires.
CONCLUSIONS: Indépendamment des méthodes de stratification des risques utilisées, le taux d'événements indésirables associés aux soins ambulatoires traitement PE semble faible. Méta-analyse basée sur notre examen systématique et une mise en commun, les patients à faible risque avec embolie pulmonaire aiguë peuvent sans risque être traités en ambulatoire si les circonstances de la maison sont suffisantes.
Coumarins (e.g., warfarin) are used for the treatment and prophylaxis of venous and arterial thromboembolism. Unfortunately, their use is limited by bleeding. In deciding whether to initiate coumarin therapy, the therapeutic benefits must be weighed against the potential risk of bleeding for each individual patient. The major determinants of coumarin-related bleeding are the intensity of anticoagulant effect as measured by the International Normalized Ratio, patient characteristics, concomitant use of other drugs, and the length of anticoagulant therapy. At the initiation of coumarin therapy, the risk factors for bleeding can be identified by the COUMARINS acronym and by one of the bleeding prediction models. During ongoing therapy with coumarins, the risks and benefits of therapy should be reassessed periodically. This article reviews the current evidence for the prediction and prevention of coumarin-related bleeding.
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.
