JC PEITHO Trial

JOURNAL CLUBBy Nicholas Ngua

Emergency UnitUHW

Fibrinolysis for Patients with Intermediate Risk Pulmonary EmbolismPEITHO Trial

Published in N Engl J Med 2014; 370:1402-1411 April 10 2014

by Meyer et al

Background Acute right ventricular pressure overload –

determinant of severity and clinical outcome for PE

Submassive PE/Intermediate risk - controversial

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?

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

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

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

Results Primary Outcome

All cause mortality or hemodynamic decompesation at 7 days

Thrombolysis 2.6% vs Placebo 5.6% (p=0.02, NNT=33)

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)

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)

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

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

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.

THE HEART PATHWAYRANDOMISED TRIALIdentifying 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

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

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 ?

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

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

Test Under Investigation The HEART Pathway

Gold Standard Usual Care No protocol Encouraged to follow ACC/AHA Guideline

Results Primary Outcome

Rate of objective cardiac testing within 30 days HEART Pathway 56.7% vs Usual Care 68.8%

(p=0.048)

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)

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

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

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