Participant Characteristics Anticoagulants Randomized Trial JAMA

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This clinical investigation that was published in The Journal of the American Medical Association (JAMA) on June 18, 2014, was a collaboration of efforts from PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL since its inception from April 10, 2014. The goal of the study was to perform a systematic review of the literature and determine prespecified inclusion criteria based on relevant studies, which are as follows: randomized controlled design in patients with Pulmonary Embolism (PE) evaluating thrombolytic therapy as an intervention; a comparator group that included any of the following agents: low-molecular-weight heparin (LMWH), vitamin K antagonist, fondaparinux, or unfractionated heparin; and reporting of mortality outcomes. Trials that were compared with different thrombolytic agents against one another or different doses of the same thrombolytic drug were not included.


Pulmonary embolism (PE) is an important cause of morbidity and mortality with more than 100,000 US cases annually and as many as 25% of patients presenting with sudden death. Pulmonary embolism is associated with increased mortality rates for up to 3 months after the index PE event. Multiple studies and meta-analyses have evaluated the role of thrombolytic therapy in PE with largely discordant results.

Several recent trials have evaluated the role of thrombolytics in PE for the patients without definitive results, particularly for the end-point of mortality. Thus, this clinical investigation performed a meta-analysis of all randomized trials of thrombolytic therapy in PE. It aimed to ascertain associations of thrombolytic therapy with bleeding risk and potential mortality benefits, with special attention paid to the subpopulation of patients presenting with intermediate-risk PE.

**Study Selection:**
Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism.

**Main Outcomes and Measures:**
The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model.

**Data Analysis:**
The primary efficacy outcome was all-cause mortality and the primary safety outcome was major bleeding. Secondary efficacy and safety outcomes were risk of a recurrent PE and ICH, respectively. Definitions of major bleeding were according to definitions in the individual trials with ICH included as a major bleeding end-point in any trial that did not prespecify this.

The mortality and major bleeding outcomes were evaluated in the 8 studies that specified therapy for hemodynamically stable PE. In addition, a prespecified analysis was planned to evaluate the primary outcomes for trials published after 2009 (to evaluate the most updated randomized evidence). A priori, another planned exploratory analysis involved the outcomes in patients older than 65 years (trials where the mean age of participants in the thrombolytic group was >65 years), as worse outcomes with thrombolytics in elderly patients have been suggested by a recent large randomized trial of the issue.

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John Snow Labs; The Journal of the American Medical Association (JAMA);

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PubMed, the Cochrane Library, Excerpta Medica dataBASE (EMBASE), EBSCO, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL)


Warfarin Side Effects, Warfarin Dosage, Warfarin Use Monitoring, Anticoagulant Therapy, Pulmonary Embolism Treatment, Novel Anticoagulants, Anticoagulant Study, JAMA Studies, Long-term Oral Anticoagulation Therapy, Anticoagulant Therapy Outcomes

Other Titles

Participant Characteristics Randomized Trial with Anticoagulant Warfarin Side Effects, Participant Characteristics Randomized Trial with Warfarin Dosage Anticoagulants, Participant Characteristics Randomized Trial with Anticoagulant Warfarin Monitoring

SourceDescription of the primary outcomes taken from previous clinical trials published after 2009.stringrequired : 1
Number_of_PatientsDescription of the number of patients involved in the clinical trials reported.integerrequired : 1 level : RAtio
Randomized_TreatmentDescription of the thrombolytic drug used for the patients in the previous clinical trials.stringrequired : 1
Dose_and_CoverageDescription of the dosage and coverage of the thrombolytic drug used for the patients in the previous clinical trials.stringrequired : 1
ComparatorDescription of the Anticoagulant drug used to compare the outcomes from the thrombolytic therapy.stringrequired : 1
Major_Bleeding_CriteriaDescription of the criteria for the bleeding outcomes based on the drug used.stringrequired : 1
Follow_Up_Effect_SizeDescription of the number of patients with major bleeding outcome.string-
Pulmonary_Embolism_LowDescription of the number of patients with low pulmonary embolism outcome.string-
Percentage_Pulmonary_Embolism_LowDescription of the percentage of patients with low pulmonary embolism outcome.numberlevel : Ratio
Pulmonary_Embolism_ModerateDescription of the number of patients with moderate pulmonary embolism outcome.string-
Percentage_Pulmonary_Embolism_ModerateDescription of the percentage of patients with moderate pulmonary embolism outcome.numberlevel : Ratio
Pulmonary_Embolism_HighDescription of the number of patients with high pulmonary embolism outcome.string-
Percentage_Pulmonary_Embolism_HighDescription of the percentage of patients with high pulmonary embolism outcome.numberlevel : Ratio
Pulmonary_Embolism_UnclearDescription of the number of patients with pulmonary embolism with unclear outcomes.integerlevel : Ratio
Percentage_Pulmonary_Embolism_UnclearDescription of the percentage of patients with pulmonary embolism with unclear outcomes.numberlevel : Ratio
AgeDescription of the age range of patients included in the clinical trials.stringrequired : 1
Mean_Range_or_Standard_DeviationDescription of either the mean or "center" of the data points; range or “difference” between the smallest value and largest values; and standard deviation or “value deviates” from the center or predicted average (y intercept).stringrequired : 1
NotesDescription of the special note/notes regarding the age range of the participants in the clinical trial.string-
Number_of_MalesDescription of the number of males included as participants in the clinical trials.integerrequired : 1 level : Ratio
Percentage_of_MalesDescription of the percentage of males included as participants in the clinical trials.numberrequired : 1 level : Ratio
Goldhaber et al, 1993101Alteplase(100 mg)HeparinICH, need for surgery5549.55650.458.54(17)4444.0
MOPETT, 2012121Alteplase(50 mg)Heparin/EnoxaparinNot prespecified8408267.73932.258.50(9.5)5545.5
Fasullo et al, 201172Alteplase(100 mg)HeparinICH, fatal, any transfusion18072100.055.97(16.12)4156.9
Jerjes-Sanchez et al, 19958Streptokinase(1 500 000 IU)HeparinNot prespecified1 to 38100.051.00(22.9)563.0
TIPES, 201058Tenecteplase(30-50 mg)HeparinICH, fatal, need for transfusion, need for surgery758100.068.10(1.85)1322.4
Konstantinides et a1, 2002256Alteplase(100 mg)HeparinICH, fatal, Hemoglobin drop >4 g/dL3015560.58031.3218.262.08(10.47)12247.6
TOPCOAT, 201483Tenecteplase(dose not reported)LMWHICH, need for surgery, Hemoglobin drop >2 g/dL with transfusion583100.055.44(14)4959.0
PEITHO, 20141005Tenecteplase(30-50 mg)Heparin/LMWH/FondaparinuxICH, life-threatening, fatal, need for transfusion301005100.066.15(15.29)47347.1
ULTIMA, 201359Alteplase(max dose 20 mg into PA over 16 h)HeparinICH, spinal, joint, RP, pericardial, Hemoglobin drop >2 g/dL with transfusion9059100.063.01(13.51)2847.5
Ly et al, 197825Streptokinase(250 000 IU loading dose, then 100 000 IU/h for 72 h)HeparinNot prespecified10Cannot exclude potential patients in this category416.028.01976.053.20(23-70)1144.0