Systematic review and meta-analysis for thrombolysis treatment in patients with acute submassive pulmonary embolism

Figures & data

Figure 1 Flow chart of literature screening.

Abbreviation: RCT, randomized controlled trial.

Table 1 Characteristics of included trials in this meta-analysis

Trial	Country	Number (thrombolysis/heparin)	Study patients		Study design		Followed by anticoagulation		Follow-up
			Inclusion	Exclusion#	Intervention	Comparison	Thrombolysis	Heparin
Levine^Citation40	Canada	33/25	Outset <15 days	Shock	Alteplase 0.6 mg/kg IV over 2 minutes	Saline solution placebo	Heparin, warfarin	Heparin, warfarin	10 days
PIOPED^Citation41	USA	9/4	Outset <7 days	Shock	Alteplase 40–80 IV over 90 minutes	Heparin	Heparin, warfarin	Heparin, warfarin	7 days
PAIMS 2^Citation42	Italy	20/16	Outset <10 days	Shock	2-hour infusion of alteplase (10 mg bolus plus 50 mg in 1 hour, plus 40 mg in 2 hours)	Heparin 1,750 IU/hour IV	Heparin, warfarin	Heparin, warfarin	7 days
Goldhaber	USA	46/55	Outset <14 days	Shock	Alteplase 100 mg IV over 2 hours	Heparin 5,000 units as initial dosage, followed by 1,000 units/hour	Heparin, warfarin	Heparin, warfarin	14 days
Konstantinides^Citation43	Germany	118/138	Outset <5 days	Hemodynamic instability	Alteplase 10 mg bolus, followed by 90 mg IV over 2 hours	Placebo	Heparin 1,000 units/hour, warfarin	Heparin 1,000 units/hour, warfarin	30 days
Becattini^Citation44	Italy	28/30	Outset <10 days	Hemodynamic disorder	Tenecteplase 30–50 mg for 5 seconds, followed by 5 mg/10 kg lV over 6 hours	Placebo	Heparin 80 IU/kg IV bolus, followed by 18 IU/kg/hour warfarin	Heparin 80 IU/kg IV bolus, followed by 18 IU/kg/hour warfarin	7 days
Fasullo^Citation45	Italy	37/35	Outset <6 hours	Hemodynamic disorder	Alteplase 10 mg bolus, followed by 90 mg IV over 2 hours	Placebo	Heparin 1,000 units/hour, warfarin	Heparin 1,000 units/hour, warfarin	180 days

Note:

# the patients with contraindications to thrombolytic drugs were excluded.

Abbreviations: IV, intravenous; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2.

Table 2 Methodological quality of included trials

Study	Randomized method	Allocation concealment	Blinding of participants	Incomplete outcome data	Selective reporting	Other potential factors	Description of withdrawal
Levine^Citation40	Unclear	Unclear	Yes	No	Unclear	Unclear	No losses
PIOPED^Citation41	Unclear	Unclear	Yes	Yes	Unclear	Unclear	No losses
PAIMS 2^Citation42	Unclear	Unclear	No	No	Unclear	Unclear	No losses
Goldhaber	Yes	Yes	No	Yes	Unclear	Unclear	Yes
Konstantinides^Citation43	Yes	Yes	Yes	Yes	Unclear	Unclear	No losses
Becattini^Citation44	Yes	Yes	Yes	No	Unclear	Unclear	No losses
Fasullo^Citation45	Yes	Unclear	Yes	No	Unclear	Unclear	No losses

Abbreviations: PIOPED, Prospective Investigation Of Pulmonary Embolism Diagnosis; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2.

Figure 2 Forest plot of the mortality compared to the thrombolysis with heparin for the patients with acute submassive PE.

Notes: The horizontal line represents 95% confidence interval of relative risk (RR), its central blue square is the position of RR, and the black diamond represents overall effect size.
Abbreviations: M–H, Mantel–Haenszel test; CI, confidence interval; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis.

Figure 3 Forest plot of recurrent PE compared to the thrombolysis with heparin for the patients with acute submassive PE.

Notes: The horizontal line represents 95% confidence interval of relative risk (RR), its central blue square is the position of RR, and the black diamond represents overall effect size.
Abbreviations: M–H, Mantel–Haenszel test; CI, confidence interval; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis.

Figure 4 Forest plot of major bleeding compared the thrombolysis with heparin for the patients with acute submassive PE.

Notes: The horizontal line represents 95% confidence interval of relative risk (RR), its central blue square is the position of RR, and the black diamond represents overall effect size.
Abbreviations: M–H, Mantel–Haenszel test; CI, confidence interval; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis.

Figure 5 Forest map of minor bleeding compared the thrombolysis with heparin for the patients of acute submassive PE.

Notes: The horizontal line represents 95% confidence interval of relative risk (RR), its central blue square is the position of RR, and the black diamond represents overall effect size.
Abbreviations: M–H, Mantel–Haenszel test; CI, confidence interval; PAIMS 2, Plasminogen Activator Italian Multicenter Study 2; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis.

Figure 6 Funnel plot of overall effect for mortality versus study precision.

Abbreviations: SE, standard error; RR, relative risk.

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