Multivessel Disease in STEMI:FIXTHECULPRITand GOBACK

TOBED!

David Cox, MDFSCAI FACCLehigh Valley Health Network

Allentown PAControversiesand Advancements

2016

Disclosure

• Medical Advisory Board: Abbott Vascular,Boston Scientific, theMedicinesCompany

Lehigh Valley Hospital

2016 YTD 533 PCI 112 STEMI 21%

FY2016 1419 PCI 333 STEMI 23%

FY2015 1293 PCI 259 STEMI 20%

What we aren’t talking about

Why th is is Im p ortan t!

Mr. and Mrs . Z’s 50 th Wedding Annivers a ry

Asweet story no one should argue with

Challenging Dogma• Everyone in shock should get all

their arteriesopened: IRAculpritand all the rest

• Doesopeningnon-culprit artery withTIMI 3 flow and segmental normalwall motion improve shockoutcomes?

P rima ry Endpoint:

Morta lity a nd/or

S e ve re re na l fa ilure 30 da ys

CULPRIT-SHOCK Tria l

Patients in ca rdiogenic shockafte r AMI

Ka the te rla bor:PCI a ll re levant s tenoses

Group 2Culprit Les ion only PCI +

potentia l s ta gedReva scula riza tion

Check In- and exclus ion crite ria

Informed consent(4 diffe rent ve rs ions)

Randomiza tion

Cath lab:PCI culprit le s ion only

Group 1Immedia te Multives se l PCI

Not suitable :CULPRIT-SHOCK

Regis try

How to win thisdebate

• A COMMON PROBLEM

• 40-50%of patientswith STEMI haveMVdisease

• Nature of non-culprit disease: a mixedbag of challenges!

How to win thisdebate

• Me: Fix the culprit IRAwith a perfectresult

Leave the rest for thoughtfulapproach—LATER!

• Tim: Just fix them all after you fixthe infarct artery…..Don’t be lazy!

NON-IRA: What we don’t know

• Fix it during infarct

• Stent before discharge…..?FFR

• Stent in a few weeks…..? FFR

• Get a stress test and go fromthere

• Fix only if symptoms

Why NOTdo all the blockages?

Benefits

• Avoid risk of second procedure• Decrease infarct size by increasing

collateral flow?• Reduce recurrent MI?• Reduce length of stay?• Reduce recurrent ischemia?

Why NOTdo all the blockages?

• Increase infarct size

–Non-IRAPCI related no-reflow, ST

• Contrast induced nephropathy

• Increase cost with no clinical benefit

• Do they all need another PCI?

• Risks

Tim is tricky: Watch out for him!

• He will quote meta-analysesthat areflawed and confounded by includingobservation registriesor RCT’swithsmall trials!

• He will show multiple anecdotalexamplesto try and prove hispoint!

JAMA. 2014;312(19):2019-2027:

2015 ACC/AHA/SCAI Focus ed Updateon PPCI for Pa tien ts With STEMI

J Am Coll Cardiol 2016;67:1235-1250

2013 Recommendation 2015 Focused Update

Recommendation

Comment

Class III: Harm Class IIb

PCI should not be

performed in a

noninfarct artery at the

time of primary PCI in

patients with STEMI who

are hemodynamically

stable. (LOE:B)

PCI of a noninfarct artery

may be considered in

selected patients with

STEMI and multivessel

disease who are

hemodynamically stable,

either at the time of

primary PCI or as a

planned staged

procedure . (LOE: B-R)

Modified

recommendation

(changed class from III:

Harm to IIb and

expanded time frame in

which multivessel PCI

could be performed).

How to win thisdebate

• Why am I right?

• Common sense!

Overes timation of Non-CulpritS tenos is Severity in STEMI (n=81)

Donmez E, e t a l. Int J Cardiovasc Imaging 2016;32:1471-1476

’Critica lly na rrowe d ’ non–culprit a rte rie s a t time of P P CI

de e me d ‘non-critica l’ during control corona ry a ngiogra phy in 13.3%

Ove re s tim a tio n o f No n -Cu lp rit S te n o s isS e ve rity in S e ttin g o f S TEMI (n =122)

Thim T, e t a l. Open Heart 2016;3:000427

Contras t dos e in CO vs MV PPCI:Increas ed Ris k of CI-AKI

Wald DS, et a l. N Engl J Med 2013;369:1115-23.Gershlick AH, e t a l. J Am Coll Cardiol 2016;65:963-72

Gurm, HS et a l. J Am Coll Cardiol 2011;58:907-914

CO (cc) MV (cc) Pvalue

PRAMI 200 (150-260) 300 (210-380) < 0.001

CVLPRIT 190 (150-250) 250 (190-330) < 0.0001

Kevin R. Bainey, Shamir R.Mehta , Tony Lai, Robert C.Wels h

Ame rica n He a rt J ourna l,

Volume 167, Is s ue 1, 2014,

1–14.e 2

Confounded: Sicker patientswith MVdzget fixed ….more likely to expire

Wald DSet al. N Engl JMed 2013;369:1115-1123 Gershlick JAm Coll Cardiol. 2015 Mar 17;65(10

PRAMI Trial: 50%or >, Same setting

Variable Preventive

PCI(N=234)

Medical Rx

(N=231)

HR(95%CI) Pvalue

Cardiac death

or MI

11 27 0.36 (0.18-0.73 0.004

Cardiac Death 4 11 0.34 (0.11-0.73) NS

Wald NEJM 2013

Cvlprit Trial: 70%or >, imd or staged

Variable Medical Rx

(N=146)

PCI

(N=150)

HR(95%CI) P

value

All-cause

mortality

6 (4.1) 2 (1.3) 0.32 (0.06,

1.60)

0.14

Heart failure 9 (6.2) 4 (2.7) 0.43 (0.13,

1.39)

0.14

FFRto guide revascularisation in non-infarct related artery territories

• Randomised 627 STEMI patientsto receive culprit-only orcomplete revascularisation staged before DC.

• FFRused to guide N-IRAPCI in complete group• FFRused if lesion diameter stenosis50-90%.

50-90% DS all had FFR: Stent if ч 0.80

or

> 90%DS(no FFR)

DANAMI 3 – PRIMULTI Trial:FFR-Guided PCI reduced revasc with

no difference in death or MI

IRAonly(n =313)

Completerevascularisation

(n =314)HR[95%CI] p

All-causedeath 11(4%) 15(5%)1·4 [0·63–

3·0]0·43

Ischemia-drivenrevascularisation*

52 (17%) 17(5%)0·31 [0·18–

0·53]<0·001

So far, RCTnot definitive

• PRAMI: 5 years to recruit, excluded many,stopped early by DSMB

• Culprit: small, MACEpositive, not individualcomponents

• Danami-3: FFRdriven if 50-90%..1/3 50-90%FFRnot ischemic

• None address issue of safety re: go home andcome back

Primary endpoint according to severity of non-infarctrelated stenosis– DANAMI-3-PRIMULTI

Add DANAMI -3 and PRAGUE

Meta analyses less convincing

combined endpoint of death / recurrent myocardial infarction.

Me ta -An a lys is o f 7 RCTsMV vs . CO-P CI S tra te g y fo r S TEMI (n =1,939)

Elgendy IY, et a l. Ca the ter Cardiovsac Interv 2016;88:501-505

Clin ic a l Ou tc o m e sOutc ome Inc id ence (Comple te %/Culp rit %) RR 95% CI P-va lue I2%

Morta lity or MI 7.8/10.4 0.69 0.42–1.12 0.14 51

MACE 14.7/24.4 0.61 0.45–0.81 <0.001 54

All-causemorta lity

4.6/5.6 0.85 0.57–1.26 0.41 0

MI 5.2/6.0 0.74 0.38–1.44 0.38 49

Urgentrevascula riza tion

9.2/19.0 0.46 0.29–0.70 <0.001 61

Major bleeding 2.2/2.5 0.83 0.41–1.71 0.62 1

Contra s t-inducednephropa thy

1.6/1.7 0.94 0.42–2.12 0.89 0

Call MomIS Tim rea lly going

to a rgue we s hould fixa ll non-cu lprit b lockages

a t the s ame time ….bas edon thes e s mall RCT’s and

mx meta ’s I can ’tunders tand?

CTOdrivesexcessmortality in MVD

• CTO in non-IRA in 10%of STEMI patients

• Reduced LV function in MVD patients mainly driven by presence of CTO

Van der Schaaf e t a l, Heart, 2006Claessen et a l. JACC: Cardiovascular Interventions , 2009

s ubs tudy from the HORIZONS-AMI tria l

Claessen BE et alEur Heart J 2012

Explore Trial Design

Patients with

STEMI + CTO

LVEFand LVEDV

MRI at 4 month

• De s ig nGloba l, multi-cente r, randomized, prospectivetwo-arm tria l with e ithe r PCI of the CTO or noCTO inte rvention afte r STEMI.Blinded eva lua tion of endpoints .

• P a tie n ts

Patients with STEMI trea ted with pPCI andwith a non-infa rct re la ted CTO.

• Ob je c tive

CTO-PCI < 7d No CTO-PCI

1:1

To de te rmine whether PCI of the CTOwithin 7 days afte r STEMI results in ahigher LVEF and a lower LVEDVassessed by MRI a t 4 months

Henriques JPet al, JACC, 2016

EXPLORETrial Outcome

- Early CTO-PCI :

- not associated with higher LVEFand lower LVEDV @ 4 months

Henriques JPet al, JACC, 2016

CTO-PCI in the LAD was associated with higher LVEF@ 4 months

47.2±12.3%vs. 40.4±11.9%, p=0.02

Henriques JPet al, JACC, 2016

COMPLETEStudy Design

Ongoing Trials

n Immediate

Strategy

Subsequent Strategy

for Untreated Non-

Culprit Lesions

FFR

Strategy

COMPARE-

ACUTE

800 Culprit Only vs

FFRGuided

Complete

Guideline Based

PCI in Culprit

Only Group

DS> 50%- FFR

(blinded in culprit

only group)

COMPLETE 3900 Culprit Only

In Both Groups

Staged Complete

Revasc (PCI)

Within 6 weeks

DS50-70%- FFRDS> 70%- Stent

FULL

REVASC

4052 Culprit Only vs

FFRGuided

Complete During

Index Admission

(Immediate or

Staged)

PRAMI CONTROL

Symptom or

ischaemia driven

revasc only. No

mandatory

ischaemia testing

DS50-90%- FFRDS> 90%- Stent

STEMI

Significant N-IRA lesion

Will the patient be better off/worse offif it is treated with PCI?

Final thoughtsWhat I have to concede to Tim:

meta of 7 RCT’sshowsno increase inCIN with MVPCI same settingorbefore DC

What Tim has to concede to me:

If Danami 3 isright and 31%of 50-90%lesionsare FFRnegative…..we willbe doinga lot of unnecessary stenting!

Final thoughts

• No one trial will likely settle thisdebate

• BEA DOCTOR..No-Reflow in IRA, don’t ’play with fire in non-IRA!

• At least we have some data to makechoices and not end up in Guideline-Jail

• More powerful studieson the way

Most of my call nights…

See what Tim comesup withBut I think….I won!