Culprit PCI vs MultiVessel PCI for Acute Myocardial Infarction

Dipti Itchhaporia, MD, FACC, FESC Trustee, American College of Cardiology

Director of Disease Management, Hoag Hospital Robert and Georgia Roth Endowed Chair for Excellence in Cardiac Care

Newport Beach, CA 37th PanHellenic Congress of Cardiology

Athens, Greece

I have no disclosures

Disclosure

Background

30-50% of STEMI patients have additional stenoses other than the infarct related artery1,2

Current guidelines support culprit vessel PCI only

Contemporary studies have, however, suggested complete revascularization3,4

Options: Multivessel PCI at the same time (preventive approach), delayed PCI (staged) or PCI later for sx or ischemia

IRA

Non culprit

1 Jong JA al. Coronary Artery disease 20062 Muller DW et al. Am Heart J 19913 Wald et al. NEJM 20134 Gershlick et al. ESC 2014

IRA Non culprit

O´Gara PT S et al. JACC 2013

2013 STEMI: ACC/AHA Guidelines

PCI is indicated in a non-infarct artery at a time separate from primary PCI in patients who have spontaneous symptoms of myocardial ischemia.

PCI is reasonable in a non-infarct artery at a time separate from primary PCI in patients with intermediate- or high-risk findings on noninvasive testing

I IIa IIb III

I IIa IIb IIIB

PCI of a non-infarct artery at the time of primary PCI in patients without hemodynamic compromise is not indicated

I IIa IIb IIIB

Studies Supporting Class III rec

Hannan JACC Int 2010

Toma EHJ 2010 Vlaar JACC 2011

N 3521 5373 40,280 (meta analysis)

Staged v late 259, 538 Non-IRA = 217 IRA only =1984

Culprit only: low mort.

In hosp mort. Staged v late

0.9 v 2.4%, p=0.04 90d MACE 12.5 v. 5.6%, P= 0.001

MV-PCI highest mort.

1 yr mort, staged v IRA only

1.3 v 3.3%, p=0.04

Non-IRA increased hazard of 90d mort. 2.44

staged PCI – lowest mortality

Take home Culprit only at index but finish job <60d

Non-IRA PCI at STEMI increased mortality

Non-IRA suitable for PCI only during a staged procedure

Rationale for ACC-AHA Guideline Recommendation • Retrospective studies & meta-analysis of nonrandomized and observational studies

Rationale for ACC-AHA Guideline RecommendationToma et al, EHJ (2010;31:1701–1707)

Let us talk about the new studies

But wait

Randomized Trial of Preventive Angioplasty in Myocardial Infarction (PRAMI)

David S. Wald, M.D., Joan K. Morris, Ph.D., Nicholas J. Wald, F.R.S., Alexander J. Chase, M.B., B.S., Ph.D., Richard J. Edwards, M.D., Liam

O. Hughes, M.D., Colin Berry, M.B., Ch.B., Ph.D., Keith G. Oldroyd, M.D., for the PRAMI Investigators

N Engl J Med Volume 369(12):1115-1123

September 19, 2013

Complete revasc

(N=234)Culprit PCI only

(N=231)HR

(95%CI) P value

Pre-specified outcomes

Cardiac death, MI, or refractory angina 21 53 0.35 (0.21-0.58) <0.001

Cardiac death or MI 11 27 0.36 (0.18-0.73) 0.004Cardiac death 4 10 0.34 (0.11-1.08) 0.07Nonfatal MI 7 20 0.32 (0.13-0.75) 0.009Refractory angina w/o CD or MI 12 30 0.35 (0.18-0.69) 0.002Secondary outcomesNoncardiac death 8 6 1.10 (0.38-3.18) 0.86Repeat revascularization 16 46 0.30 (0.17-0.56) <0.001

Median FU 2.3 YearsWald DS et al. N Engl J Med 2013;369:1115-1123

PRAMI: “Preventative” PCI of Non-culprit Lesions after Culprit Lesion Primary PCI in STEMI

Preventive PCI No preventive PCI

21

HR 0.35, p<0.001 (95% CI 0.21-0.58)

65% risk reduction

PRAMI – cardiac death, non fatal MI, refractory angina

N=234 N=231

Wald et al. NEJM 2013

53

PRAMI Trial Conclusions •The preventive multivessel PCI group had a 65% reduction in the relative risk of the primary outcome ( composite of cardiac death, nonfatal MI, or refractory angina) as compared to Culprit PCI group. •Relatively small population •Distribution of composite endpoint differed significantly in their frequency, (e.g. cardiac death=14, nonfatal MI = 27, refractory angina = 42.) •Thus, P values are extremely sensitive to the addition of few events. Only 3 more MIs in the preventive PCI arm would render nonfatal MI non-significant.

A.H. Gershlick, G.P. McCann et al JACC

MARCH 17, 2015

Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing

Primary PCI for STEMI and Multivessel Disease: The CvLPRIT Trial

CvLPRIT study: Complete vs IRA PCI in STEMI

1. 296 STEMI pts-Randomized to complete revascularization( n=150) vs infarct related revascularization (n=146) only.

2. Complete revascularization was performed either at the time of primary PCI or before hospital discharge.

3. Randomization was stratified by infarct location- anterior vs non-anterior and by symptom onset- less than 3 hours or more than 3 hours

4. Primary endpt was a composite of all cause death, recurrent myocardial infarction, heart failure, and ischemia –driven revascularization within 12 months

Cvlprit – Primary Endpoint : 12 Month MACE: Total mortality, Recurrent MI, Heart failure, Revascularization

Gershlick et al. ESC 2014

CvLPRIT Results1. The primary endpoint occurred in 10% of the complete

revascularization group versus 21.2% in the culprit only revascularization group

2. A trend toward benefit was seen early after complete revascularization

3. No significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen.

4. Small study but significant outcome

STEMI Meta-analysis

1. ESC- 2014: CvLPRIT investigator Dr. Anthony Gershlick of the University of Leicester (England) presented a meta-analysis combining the weighted results of PRAMI, CvLPRIT, and two earlier randomized trials: HELP AMI ( Int. J. Cardiovasc. Intervent. 2004;6:128-33 ) and an Italian trial ( Heart 2010;96:662-7 ).

2. The results strongly favored multivessel PCI, with a 45% reduction in mortality and a 61% decrease in recurrent MI, compared with culprit vessel–only PCI at the time of admission for STEMI.

Randomise conventional PPCI, iPOST, deferred stenting

627 Multivessel disease at two centres over a 3 year period

313 IRA PCI only 314 FFR guided complete revascularisation

STEMI < 12 hours

Randomise

(>50% stenosis in non IRA > 2 mm suitable for PCI)

Successful infarct related artery PCI

Primary endpoint- DANAMI3-PRIMULTI median follow up 27 months

Composite 1. All-cause mortality2. Nonfatal MI3. Ischemia driven revascularization of non IRA lesions

  IRA only(n = 313)

Complete revascularization

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

Primary endpoint 68 (22%) 40 (13%) 0·56 [0·38 – 0·83] 0·004 All-cause death 11 (4%) 15 (5%) 1·4 [0·63 – 3·0] 0·43

Nonfatal MI 16 (5%) 15 (5%) 0·94 [0·47 – 1·9] 0·87

Ischemia-driven revascularisation* 52 (17%) 17 (5%) 0·31 [0·18 – 0·53] <0·001

Secondary endpoints         Cardiac death 9 (3%) 5 (2%) 0·56 [0·19 – 1·7] 0·29

Cardiac death or nonfatal MI 25 (8%) 20 (6%) 0·80 [0·45 – 1·45] 0·47

Urgent PCI 18 (6%) 7 (2%) 0·38 [0·16 – 0·92] 0·03

Non-urgent PCI 27 (9%) 8 (3%) 0·29 [0·13 – 0·63] 0·002

DANAMI3-PRIMULTI

* PCI or CABG

Individual components of primary endpoint

Composite

Non fatal MI All cause death

Revascularisation

Subgroup analysis- DANAMI3-PRIMULTI Number of patients Events Hazard Ratio (95% CI) Pinteraction

627 108 0.56 (0.34–0.83)506 88 0.53 (0.34 – 0.82) 0.5121 20 0.75 (0.31 – 1.8)         

339 55 0.33 (0.18 – 0.60) 0.02288 53 0.89 (0.52 – 1.5)         

556 94 0.56 (0.37 – 0.85) 1.071 14 0.55 (0.17 – 1.7)         

410 72 0.67 (0.42 – 1.1) 0.2217 36 0.38 (0.18 – 0.79)  

583 102 0.60 (0.40 - 0.89) -44 6 -  

* there were no events in patients with prior myocardial infarction randomized to complete revascularization

Conclusions : DANAMI3-PRIMULTI

Complete FFR guided revascularization of multivessel CAD in STEMI pts, staged within the index admission, reduced all cause death, reinfarction and repeat revascularization

40% of repeat revascularizations were urgent

Analysis of secondary endpoints showed no difference between groups with regards to all cause death or non fatal re-infarction

PRAGUE 13 Trial

1. 106 pts underwent complete revascularization ( staged day 3- 40- days after intervention) vs 108 pts who received Culprit only PCI

2. Primary composite endpt included all cause death, nonfatal MI and stroke 16% in the pts with multivessel PCI vs 13.9% culprit PCI

3. All cause mortality was 5.7% for multivessel PCI vs 6.5% culprit PCI

4. Bottom line: Demonstrated no difference in favor of

Contemporary Randomized STEMI MVD Trials – Complete Revascularization?

Do All now Do All, stage Do all now use FFR

Date of download: 8/7/2016 Copyright © The American College of Cardiology. All rights reserved.

From: COMPLETE VERSUS CULPRIT-ONLY REVASCULARIZATION IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION AND MULTIVESSEL DISEASE: A META-ANALYSIS OF RANDOMIZED TRIALS

J Am Coll Cardiol. 2016;67(13_S):41-41. doi:10.1016/S0735-1097(16)30042-0

2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention

A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions

© American College of Cardiology Foundation and American Heart Association, Inc. IIB

New Focused PCI guidelines update- October 21, 2015

Conclusions

1. In the past, PCI of nonculprit vessel was Class III- harm 2. Now we have new evidence from recent clinical trials that

treating nonculprit vessels maybe safe and beneficial in selected pts with multivessel disease.

3. ACC withdraws from its ‘Choosing Wisely’ campaign its former recommendation discouraging multivessel revascularization at the time of primary PCI for STEMI. The college cited “new science showing that complete revascularization of all significant blocked arteries leads to better outcomes in some heart attack patients.”

Conclusions

1. New focused update published October 21, 2015 states that treating nonculprit vessel maybe considered in pts with STEMI (Class IIb recommendation)

2. The best timing to treat non-culprit arteries is not known 3. The focused update states ”physicians should integrate

clinical data, lesion severity/complexity and risk of contrast nephropathy to determine optimal strategy.

4. Await Results of the COMPLETE Study- led by Dr Shamir Mehta at McMaster involves 4,000 pts with STEMI and have multivessel disease. Also Compare Acute Trial – Randomized 885 patients, to be completed Nov 2016