This randomized controlled trial compared tenecteplase to placebo in 1,005 patients with intermediate risk pulmonary embolism. Patients receiving tenecteplase had a lower combined rate of all-cause mortality or hemodynamic decompensation at 7 days compared to placebo (2.6% vs 5.6%), but they also experienced higher rates of major extracranial bleeding (6.3% vs 1.3%) and stroke (2.4% vs 0.2%). The study demonstrates that thrombolysis reduces early adverse outcomes in intermediate risk PE, but is associated with increased bleeding risks.

1. JOURNAL CLUB
By Nicholas Ngua
Emergency Unit
UHW

2. Fibrinolysis for Patients with
Intermediate Risk Pulmonary
Embolism
PEITHO Trial
Published in N Engl J Med 2014; 370:1402-1411
April 10 2014
by Meyer et al

3. Background
 Acute right ventricular pressure overload –
determinant of severity and clinical outcome for
PE
 Submassive PE/Intermediate risk -
controversial

4. Clinical Question
 Among patients with submassive PE being
treated with unfractionated heparin, does
administration of tenecteplase reduce all-cause
mortality or hemodynamic decompensation at
7 days when compared to placebo?

5. Design
 Multicenter, randomised, double-blind, placebo
controlled trial
 N = 1,005
 Tenecteplase (n=506)
 Placebo (n=499)
 Setting : 76 centers in 13 countries
 Enrollment : 2007 – 2012
 Follow up : 30 days
 Analysis : Intention to treat

6. Population
Inclusion Criteria
 ≥ 18 yr old
 Confirmed PE with
symptoms ≤ 15 days
 RV dysfunction as
defined by
(RVID/LVID >0.9)
 ECHO
 CT Angio
 Elevated Trop
Exclusion Criteria
 Hemodynamic
collapse
 Coagulopathy
 Use of
thrombolytics/IVC
filters/p.
thrombectomy in
prior 4 days
 Uncontrolled HTN

7. Intervention
 Tenecteplase 30mg-50 mg IV – by weight
Control
 Placebo
Both group initiated on UFH immediately after
randomisation with goal aPTT 2.0-2.5X

8. Results
 Primary Outcome
 All cause mortality or hemodynamic
decompesation at 7 days
 Thrombolysis 2.6% vs Placebo 5.6% (p=0.02,
NNT=33)

9. Results
 Secondary Outcome
 All cause mortality at 7 days
 Thrombolysis 1.2% vs Placebo 1.8% (p=0.42)
 All cause mortality at 30 days
 Thrombolysis 2.4% vs Placebo 3.2% (p=0.42)
 Hemodynamic decompensation at 7 days
 Thrombolysis 1.6% vs Placebo 5.0% (p=0.002,
N=29)
 Recurrent PE at 7 days
 Thrombolysis 0.2% vs Placebo 1.0% (p=0.12)

10. Results
 Adverse Events
 Bleeding at 7 days
 Major Extracranial
 Thrombolysis 6.3% vs Placebo 1.3 % (p<0.001, NNH
= 20)
 Stroke at 7 days
 Thrombolysis 2.4% vs Placebo 0.2 % (p=0.003,
NNH = 45)

11. Results
 Subgroup Analysis (Death & Hemodynamic
Decompensation)
 ≤ 75 yrs : Thrombolysis 1.7% vs Placebo 5.1%
 > 75 yrs : Thrombolysis 4.3% vs Placebo 6.7%
 p=0.36
 Subgroup Analysis (Major Extracranial Bleeding)
 ≤ 75 yrs : Thrombolysis 4.1% vs Placebo 1.5%
 > 75 yrs : Thrombolysis 11.1% vs Placebo 0.6%
 p=0.09

12. Conclusion
 Those intermediate risk PE, primary outcome of
early death or hemodynamic decompensation
was reduced after treatment with thrombolysis
but associated with significant increase in risk
of intracranial and other major bleeding

13. Questions
 What is the primary outcome of this study? Do
you think this is appropriate?
 What is intention to treat analysis? Give two
advantages and two disadvantages of this
method of analysis.
 At the end of this journal club, Dr Jo Mower asks
you whether it should be introduced in your
department. Give reasons to support your
stand.

14. THANK YOU
 Next Journal Club on 26 August 2015
 Feedback on how to improve journal club