This document summarizes two randomized controlled trials related to pulmonary embolism and chest pain management. The first trial found that thrombolysis with tenecteplase for intermediate risk pulmonary embolism reduced mortality and decompensation at 7 days compared to placebo, but increased bleeding risks. The second trial found that using the HEART pathway criteria for chest pain allowed for fewer cardiac tests, more early discharges, and shorter hospital stays compared to usual care, without increasing safety 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. THE HEART PATHWAY
RANDOMISED TRIAL
Identifying Emergency Department Patients With Acute
Chest Pain for Early Discharge
Circ Cardiovasc Qual Outcomes. 2015;8:195-203,
published online before print March 3 2015
by Mahler et al

15. Background
 US trial
 AHA guideline - objective cardiac testing for low
risk - resource, low pick up rate
 Observational study using HEART pathway able
to early discharge >20% patients with acute
chest pain
 with negative predictive value (NPV) for a
MACE >99% at 30 days

16. Clinical Question
 Can HEART Pathway meaningfully reduce
objective cardiac testing, increase early
discharges and reduce index hospital length of
stay compared with usual care while
maintaining high sensitivity & NPV (99%) for
MACE ?

17. Design
 Randomised Controlled, Single-center
 N = 282
 HEART Pathway (n=141)
 Usual Care (n=141)
 Setting : Tertiary academic center in US (104,000
patients per year with 24hr consultant cover)
 Convenience Sampling (6 days excluding Saturday,
80 hours per week)
 Stratified Randomisation (presence of known
coronary disease including previous
revascularisation)
 Enrollement : Sept 2012 – Feb 2014

18. Population
Inclusion Criteria
 ≥ 21 yr old
 ACS symptoms
 ECG
 Troponin (ADVIA Centaur
platorm TnI-Ultra assay)
Exclusion Criteria
 New STE
 Hypotension
 Life expectancy < 1 yr
 Non cardiac
 Previous enrollment
 Non English speaking
 Incapacity/unwilling
to consent

19. Test Under Investigation
 The HEART Pathway
Gold Standard
 Usual Care
 No protocol
 Encouraged to follow ACC/AHA Guideline

22. Results
 Primary Outcome
 Rate of objective cardiac testing within 30 days
 HEART Pathway 56.7% vs Usual Care 68.8%
(p=0.048)

23. Results
 Secondary Outcome
 Early discharge rate
 HEART Pathway 39.7% vs Usual Care 18.4%
(p=0.0001)
 Index LOS
 HEART Pathway 9.9 hours vs Usual Care 21.9
hours (p=0.013)
 Safety Events
 MACE within 30 days
 0 in all low risk HEART Pathway (n=66)

24. Conclusion
 Use of HEART Pathway significantly decreased
objective testing, early discharge rate of ~40 %,
cut median LOS by 12 hours.
 No MACE at 30 days

25. Questions
 Comment on the trial randomisation
 What is allocation concealment? Was this
present in this study?
 Give three strengths & three limitations of this
trial
 At the end of this journal club, Dr Jo Mower asks
you whether it should be introduced in your
department. Give four reasons why you might
want to institute in your department

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