JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 68, NO. 10, 2016

2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jacc.2016.05.086

REVIEW TOPIC OF THE WEEK

PCI Strategies in Patients With

ST-Segment Elevation Myocardial
Infarction and Multivessel
Coronary Artery Disease
Eric R. Bates, MD,a Jacqueline E. Tamis-Holland, MD,b John A. Bittl, MD,c Patrick T. OGara, MD,d
Glenn N. Levine, MDe

ABSTRACT
Recent randomized controlled trials have suggested that patients with ST-segment elevation myocardial infarction and
multivessel coronary artery disease may benet more from multivessel percutaneous coronary intervention (PCI)
compared with culprit vessel-only primary PCI. The American College of Cardiology, American Heart Association, and
Society for Cardiovascular Angiography and Interventions recently published an updated recommendation on this topic.
The purpose of this State-of-the-Art Review is to accurately document existing published reports, describe their limitations, and establish a base for future studies. (J Am Coll Cardiol 2016;68:106681)
2016 by the American College of Cardiology Foundation.

pproximately 50% of patients with ST-

(SCAI) guideline for percutaneous coronary inter-

segment

infarction

vention (PCI) and the 2013 ACCF/AHA guideline for

(STEMI) have multivessel (MV) coronary ar-

STEMI recommended that primary PCI should not be

tery disease (CAD) (1). The short-term prognosis after

performed (Class III, Harm) in a noninfarct artery in

STEMI is worse with MV CAD than with single-vessel

patients with STEMI who are hemodynamically stable

CAD (24), perhaps because of additional plaque

(10,11). Additionally, the American College of Cardi-

instability

perfusion

ology (ACC) Appropriate Use Criteria Task Force

caused by endothelial dysfunction, microvascular

labeled PCI of a noninfarct artery at the time of

(5,6);

elevation

impaired

myocardial

myocardial

spasm, or inammation (7); or decreased contractility

primary PCI as inappropriate (12). These recom-

in noninfarct zones (2,8). The long-term prognosis is

mendations arose from historical safety concerns

also worse because of older age, more atherosclerotic

that included an increased potential for procedural

risk factors, higher atherosclerotic disease burden,

complications,

and lower left ventricular ejection fraction in patients

thrombosis. However, more complete acute revascu-

with MV CAD (9).

larization in patients with STEMI may be safer in the

The 2011 American College of Cardiology Founda-

contrast

nephropathy,

current era due to advances in stent technology and

antiplatelet therapy; might decrease mortality, rein-

Society for Cardiac Angiography and Interventions

farction, and repeat revascularization rates; and

(ACCF)/American

Heart

Association

Listen to this manuscripts

audio summary by
Dr. Valentin Fuster.

stent

(AHA)/

tion

JACC Editor-in-Chief

and

From the aDivision of Cardiovascular Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann
Arbor, Michigan; bDivision of Cardiology, Department of Internal Medicine, Mount Sinai St. Lukes Hospital, New York, New York;
c

Munroe Heart and Vascular Institute, Munroe Regional Medical Center, Ocala, Florida; dCardiovascular Division, Department of

Internal Medicine, Brigham and Womens Hospital, Boston, Massachusetts; and the eSection of Cardiology, Michael E. DeBakey
Medical Center, Baylor College of Medicine, Houston, Texas. The authors have reported that they have no relationships relevant
to the contents of this paper to disclose.
Manuscript received March 3, 2016; revised manuscript received April 19, 2016, accepted May 10, 2016.

JACC VOL. 68, NO. 10, 2016

Bates et al.

SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

1067

could reduce hospital length of stay, resource utili-

primary endpoints, and quantitative mortal-

ABBREVIATIONS

zation, and cost. In fact, several recent randomized

ity results; and separated MV primary PCI and

AND ACRONYMS

controlled trials and meta-analyses have supported

staged PCI results. Qualitative results for

this strategy (see later discussion). In response to

MACE, reinfarction, and repeat revasculari-

these reports, the ACC removed the 2012 proscription

zation were tabulated because the studies

against MV primary PCI from the American Board of

were too heterogeneous to permit an accurate

Internal

Wisely

quantitative analysis. Twelve reports were

AHA = American Heart

Campaign in 2014 (13). Additionally, the 2014 Euro-

excluded from this analysis: 4 included pa-

Association

pean Society of Cardiology (ESC)/European Associa-

tients with nonST-segment elevation acute

BCI = Bayesian condence

tion for Cardio-Thoracic Surgery (EACTS) Guidelines

coronary syndromes (2124); 3 did not sepa-

interval

on Myocardial Revascularization and the 2015 ACC/

rate MV primary PCI from staged PCI (2527);

CAD = coronary artery disease

AHA/SCAI Focused Update on Primary PCI committee

2 compared complete versus incomplete

CI = condence interval

assigned

CVO = culprit-vessel only

Medicine

Foundation

new

Class

IIb

Choosing

ACC = American College of

Cardiology

ACCF = American College of

Cardiology Foundation

recommendation,

revascularization (28,29); 2 studied patients

concluding that MV primary PCI may be considered in

with heart failure and cardiogenic shock

ESC = European Society of

selected hemodynamically stable patients with sig-

(30,31); and 1 compared MV primary PCI with

Cardiology

nicant noninfarct artery stenoses (14,15).

single-vessel primary PCI (32).

FFR = fractional ow reserve

Nevertheless, the best strategy for the treatment of

To illustrate the relative effectiveness of

MACE = major adverse

the noninfarct artery in patients with STEMI and MV

CVO versus MV PCI, we used conventional

cardiovascular event(s)

CAD remains an unresolved issue, with important

statistical methods to create forest plots to

MV = multivessel

implications for potentially improving clinical out-

illustrate differences in mortality rates, a

OR = odds ratio

comes in these patients. PCI strategies include: 1)

relevant

culprit vessel-only (CVO) primary PCI with continued

comparing primary PCI strategies in patients

medical management and PCI of noninfarct arteries

with STEMI and MV CAD. We applied a

endpoint

reported

in

all

trials

PCI = percutaneous coronary

intervention

SCAI = Society for

Cardiovascular Angiography

only for spontaneous angina or myocardial ischemia

random effects model to acknowledge the

on stress testing; 2) MV PCI at the time of primary PCI;

variation in study design, treatment dura-

or 3) CVO primary PCI, followed by staged PCI of

tion, and length of follow-up among the

noninfarct arteries later during the index hospitali-

studies. For inductive inference and to

zation or soon after hospital discharge (Central

emulate the random effects model, we used hierar-

Illustration). This review summarizes the data on PCI

chical Bayesian meta-analysis. In the absence of

for patients with STEMI and MV CAD (15).

strong evidence for the superiority of 1 strategy over

and Interventions

STEMI = ST-segment elevation

myocardial infarction

The terms preventive angioplasty (16) and complete

another, we used noninformative priors dened by a

revascularization (1720) have previously been used

treatment effect of 0.00 and precision of 0.0001 to

to describe what we are presently naming MV primary

ensure that the posterior inference would be domi-

PCI and staged PCI. We prefer these terms because

nated by the likelihood of the data (33,34). All ana-

the term preventive has traditionally been used to

lyses were intention-to-treat. Standard meta-analysis

describe noninvasive interventions that attempt to

was performed using the open-source statistical pro-

prevent invasive interventions or major adverse

gram R 3.0.2 and the library package meta 3.8-0 (35).

cardiovascular events (MACE), and because complete

Bayesian computations were run with the open-

revascularization was not routinely attempted in pa-

source program OpenBUGS 3.2.3 (Open Bayesian

tients with chronic total occlusions, other complex

Inference Using Gibbs Sampling), using Markov chain

lesions, or smaller arteries.

Monte Carlo modeling (34,36), linked to R with BRugs

(37).

METHODS

CVO VERSUS MV PRIMARY PCI. We identied 6

A search of the published reports was performed us-

single-center (3843), 8 multicenter (4451), and 3

ing the PubMed database through December 2015. We

case-controlled (5254) observational reports that

included in our analysis previously published reports

compared CVO versus MV primary PCI (Table 1). In

that

and

general, in the current era with new-generation stent

any additional studies that were independently

implantation and dual antiplatelet therapy, there

identied. When possible, we excluded patients with

appeared to be no increased risk for reinfarction when

nonST-segment elevation myocardial infarction,

asymptomatic periprocedural myocardial biomarker

hemodynamic instability, prior brinolytic therapy,

elevations were not counted as events. The risk for

and prior coronary artery bypass surgery. We docu-

repeat revascularization was inconsistently lower

mented

with MV primary PCI in these studies, but was never

were

cited

study

in

design

previous

and

publications

enrollment

periods,

1068

Bates et al.

JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

C E NT R A L I LL U ST R A T I O N PCI Strategies in Patients With STEMI and MV Disease: CVO Primary PCI Versus MV PCI
Strategies

Culprit vessel-only primary PCI

Multivessel primary PCI

Staged PCI

Initial
procedure

Culprit vessel-only PCI

Culprit vessel PCI

and non-culprit vessel PCI

Culprit vessel-only PCI

Daysweeks
later

Non-culprit vessel PCI

for spontaneous ischemia
or intermediate/high risk findings
on noninvasive testing
Reduced contrast volume
Reduced risk of
PCI complications

Pros

Non-culprit vessel PCI

Decreased repeat
revascularization
Decreased hospital length of stay

Time to assess benefit vs. risk

of non-culprit vessel PCI

Prolonged procedure time

Increased repeat
revascularization risk
Cons

Potential reduction in LV recovery

Increased contrast volume

Increased periprocedural MI risk

Additional PCI access risk

Additional procedure costs

Potentially unnecessary PCI of

functionally insignificant stenosis

Bates, E.R. et al. J Am Coll Cardiol. 2016;68(10):106681.

Patients with ST-segment elevation myocardial infarction (STEMI) and multivessel (MV) coronary artery disease may undergo percutaneous coronary intervention (PCI)
using 1 of 3 strategies: 1) culprit vesselonly (CVO) primary PCI; 2) primary PCI followed by MV intervention of additional noninfarct lesions at the time of the primary
procedure; or 3) CVO primary PCI followed by staged PCI of noninfarct lesions later during the index hospitalization or after hospital discharge. Advantages and disadvantages of each strategy are illustrated. LV left ventricular.

contrasted with the total number of additional non-

(17% vs. 35%), but no differences in death or rein-

infarct artery PCI procedures performed initially

farction rates.

to obtain that result. We observed a nonsignicant

Politi et al. (18) randomized 214 patients to CVO

reduction in long-term mortality with CVO compared

primary PCI, MV primary PCI, or staged PCI. Again,

with MV primary PCI using both traditional statistical

repeat revascularization rates were lower with MV

approaches (odds ratio [OR]: 0.83; 95% condence

primary PCI, but there were no differences in death or

interval [CI]: 0.62 to 1.09) and Bayesian approaches

reinfarction rates.

(posterior median OR: 0.83; 95% Bayesian condence

interval [BCI]: 0.59 to 1.15) (Figure 1).

The PRAMI (Preventive Angioplasty in Acute

Myocardial Infarction) trial screened 1,922 patients

Four randomized trials (1619) compared CVO to

and enrolled 465 patients at 5 sites over 5 years (16).

MV primary PCI (Table 2). MACE, reinfarction, and

Recruitment was stopped prematurely by the data

repeat revascularization rates were lower with MV

safety and monitoring board with a mean follow-up of

primary PCI. We observed a nonsignicant increase

23 months due to signicant differences between

in long-term mortality with CVO compared with MV

groups. The sample size was on the basis of an ex-

primary PCI using both traditional statistical ap-

pected annual MACE rate of 20% for CVO primary PCI

proaches (OR: 1.69; 95% CI: 0.98 to 2.89) and Bayesian

and a 30% risk reduction for MV primary PCI at 80%

approaches (OR: 1.66; 95% BCI: 0.84 to 3.28)

power. Thirteen patients did not receive assigned

(Figure 2).

therapy, and 18 were lost to follow-up. The composite

The HELP-AMI (Hepacoat for Culprit or Multivessel

primary outcome of cardiac death, nonfatal reinfarc-

Stenting for Acute Myocardial Infarction) trial ran-

tion, or refractory angina occurred in 21 (9%) patients

domized 69 patients in a 3:1 ratio to MV or CVO pri-

treated with MV primary PCI compared with 53 (22%)

mary PCI (17). There was a nonsignicant reduction

patients treated with CVO primary PCI (hazard ratio

in repeat revascularization with MV primary PCI

[HR]: 0.35; 95% CI: 0.21 to 0.58; p < 0.001). There

JACC VOL. 68, NO. 10, 2016

Bates et al.

SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

T A B L E 1 Observational Trials of CVO Versus MV Primary PCI

First Author (Ref. #)

Year

Design

CVO

MV

61

68

Primary
Endpoint

Follow-Up
(Months)

Mortality,
n (%)

Outcomes for
MV

D, MI, revasc

CVO: 10 (16)
MV: 17 (25)

MACE, MI, revasc similar

Mortality similar

Roe (52)
2001

Case-controlled
Multicenter
19951999

Corpus (38)
2004

Registry
Single-center
19982002

354

26

D, MI, revasc

12

CVO: 42 (12)
MV: 5 (19)

MACE, MI, revasc similar

Mortality similar

Khattab (39)
2008

Sequential cohort
Single-center
20042005

45

28

D, MI, revasc

12

CVO: 3 (7)
MV: 2 (8)

MACE, MI, revasc similar

Mortality similar

Qarawani (40)
2008

Retrospective
Single-center
20012004

25

95

D, MI, CHF, ischemia

12

CVO: 2 (8)
MV: 9 (9.4)

MACE, MI, revasc lower

Mortality similar

Varani (41)
2008

Registry
Single-center
20042007

156

147

Mortality

CVO: 10 (6.6)
MV: 15 (9.9)

Mortality similar

Cavender (44)
2009

Registry
Multicenter
20042007

23,146

2,701

Mortality

In-hospital

CVO: 586 (2.5)

MV: 88 (3.3)

MACE similar
Mortality similar*

Hannan (53)
2010

Case-controlled
Multicenter
20032006

458

458

Mortality

42

CVO: 31 (6.7)
MV: 48 (10.4)

Mortality similar

Toma (45)
2010

Subgroup
Multicenter
20042007

1,984

217

Mortality

CVO: 111 (5.6)

MV: 27 (12.5)

Mortality higher

Dziewierz (46)
2010

Registry
Multicenter
20052007

707

70

Mortality

12

CVO: 57 (8.1)
MV: 11 (15.7)

Mortality similar*

Mohamad (42)
2011

Retrospective
Single-center
20022006

30

Mortality

12

CVO: 3 (10)
MV: 2 (28.6)

MACE similar
Mortality similar

Bauer (47)
2013

Registry
Multicenter
20052008

2,118

419

Mortality

In-hospital

CVO: 72 (3.4)
MV: 6 (1.4)

MI higher
Mortality similar*

Jaguszewski (48)
2013

Registry
Multicenter
20052012

3,833

1,108

Mortality

In-hospital

CVO: 68 (4.4)
MV: 81 (7.3)

MI similar
Mortality similar*

Santos (49)
2014

Registry
Multicenter
20102011

180

77

Mortality

In-hospital

CVO: 14 (7.8)
MV: 2 (2.6)

MI similar
Mortality similar*

Jeger (50)
2014

Registry
Multicenter
20052012

1,467

442

Mortality

12

CVO: 40 (2.7)
MV: 12 (2.7)

MI similar
Revasc lower
Mortality similar

Kim (43)
2014

Registry
Single-center
20062009

155

67

D, MI, revasc

36

CVO: 15 (9.7)
MV: 5 (7.4)

MACE, MI, revasc similar

Mortality similar

Manari (51)
2014

Registry
Multicenter
20022010

706

367

D, MI, TVR

24

CVO: 127 (18.0)

MV: 26 (7.1)

MI, MACE lower

Revasc similar
Mortality lower

Iqbal (54)
2014

Case-controlled
Multicenter
20042011

2,418

403

Mortality

12

CVO: 164 (6.8)

MV: 41 (10.2)

MACE (in-hospital) higher

Mortality higher*

*Adjusted mortality rates.

CHF congestive heart failure; CVO culprit vessel-only; D death; MACE major adverse cardiovascular events; MI myocardial infarction; MV multivessel; PCI
percutaneous coronary intervention; revasc repeat revascularization; TVR target vessel revascularization.

were statistically signicant reductions in the com-

expected MACE rate of 37% for CVO primary PCI and

posite of death and myocardial infarction, and in re-

22% for MV PCI at 80% power. Eighteen patients

fractory angina and repeat revascularization rates in

crossed over, and 19 were lost to follow-up. MV pri-

favor of MV primary PCI.

mary PCI was performed in 97 patients, and staged

The CvLPRIT (Complete Versus Culprit-Lesion

PCI was performed in 42 patients. The composite

Only Primary PCI) trial screened 850 patients and

primary outcome of all-cause death, reinfarction,

enrolled 296 patients at 7 sites over 2 years (19).

heart failure, and ischemia-driven revascularization

The sample size was calculated on the basis of an

at 12 months occurred in 15 (10%) patients with

1069

1070

Bates et al.

JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

F I G U R E 1 Forest Plot of Mortality in Observational Studies Comparing CVO With MV Primary PCI

CULPRIT
Events
Total

Study

Odds Ratio (OR)

MULTIVESSEL
Events Total

Roe (2001)
13
79
19
79
Corpus (2004)
42
354
5
26
Qarawani (2008)
2
25
9
95
Khattab (2008)
3
45
2
28
Varani (2008)
8
156
12
147
Cavender (2009)
1321 25802
246 3134
Hannan (2010)
54
503
59
503
Toma (2010)
111
1984
27
217
Dziewierz (2010)
57
707
11
70
Mohamad (2011)
3
30
2
7
Bauer (2013)
72
2118
6
419
Jaguszewski (2013)
168
3833
81 1108
Santos (2014)
14
180
2
77
Jeger (2014)
40
1467
12
442
Kim (2014)
15
155
5
67
Manari (2014)
127
706
26
367
Iqbal (2014)
164
2418
41
403
Bayesian hierarchical meta-analysis
Fixed effect model
2214 40562
565 7189
Random effects model
Heterogeneity: Isquared=76.6%, tausquared=0.1929, p<0.0001
0.1

0.2

0.5

CVO Better

OR

95%CI

0.62
0.57
0.83
0.93
0.61
0.63
0.91
0.42
0.47
0.28
2.42
0.58
3.16
1.00
1.33
2.88
0.64
0.83
0.75
0.83

[0.28; 1.37]
[0.20; 1.58]
[0.17; 4.11]
[0.15; 5.93]
[0.24; 1.53]
[0.55; 0.73]
[0.61; 1.34]
[0.27; 0.65]
[0.23; 0.95]
[0.04; 2.11]
[1.05; 5.61]
[0.44; 0.76]
[0.70; 14.27]
[0.52; 1.93]
[0.46; 3.82]
[1.85; 4.48]
[0.45; 0.92]
[0.59; 1.15]
[0.67; 0.82]
[0.62; 1.09]

10

MV Better

Mortality rates at longest follow-up are obtained from the studies described in Table 1 comparing culprit vesselonly (CVO) to multivessel (MV)
coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) and MV coronary artery disease (CAD). CI condence interval.

MV PCI compared with 31 (21%) patients with CVO

It should be noted that 2 of the randomized trials

primary PCI (HR: 0.45; 95% CI: 0.24 to 0.84;

that tested CVO versus MV primary PCI included

p 0.009). There were no statistically signicant

patients with staged PCI (18,19), with the results

differences in death, reinfarction, heart failure, or

often included as MV primary PCI in meta-analyses.

repeat revascularization rates, although the trends

Four other randomized trials have tested CVO pri-

favored MV PCI.

mary PCI versus staged PCI (20,5558), with 2 using

T A B L E 2 Randomized Controlled Trials of CVO Versus MV Primary PCI

First Author (Ref. #)

Year

Design

CVO
(n)

MV
(n)

Primary
Endpoint

Follow-Up
(Months)

Mortality
(n)

CV Death
(n)

MI
(n)

Revasc
(n)

12

0 vs. 1

0 vs. 1

1 vs. 1

6 vs. 9

Di Mario (17)
2004

Randomized
multicenter
2004

17

52

Revasc

Politi (18)
2010

Randomized
single-center
20032007

84

65*

Death, MI, rehosp

for ACS, revasc

30, mean

13 vs. 6

10 vs. 4

7 vs. 2

28 vs. 6

Wald (16)
2013

Randomized
multicenter
20082013

231

234

CV death,
MI,
refractory angina

23, mean

16 vs. 12

10 vs. 4

20 vs. 7

46 vs. 16

Gershlick (19)
2015

Randomized
multicenter
20112013

146

150

Death, MI, HF, revasc

12

10 vs. 4

7 vs. 2

4 vs. 2

16 vs. 8

478

501

39 vs. 23

27 vs. 11

32 vs. 12

96 vs. 39

Pooled

*Excludes 65 patients randomized to staged PCI. Includes 42 patients who underwent staged PCI.
ACS acute coronary syndrome; CV cardiovascular; HF heart failure; rehosp rehospitalization; other abbreviations as in Table 1.

JACC VOL. 68, NO. 10, 2016

Bates et al.

SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

1071

F I G U R E 2 Forest Plot of Mortality in Randomized Controlled Trials Comparing CVO With MV Primary PCI

Di Mario (2004)
0
Politi (2010)
13
Wald (2013)
16
Gershlick (2014)
10
Bayesian hierarchical meta-analysis

Odds Ratio (OR)

MULTIVESSEL
Events Total

CULPRIT
Events Total

Study

17
84
231
146

1
6
12
4

52
65
234
150

Fixed effect model

39 478
23
501
Random effects model
Heterogeneity: Isquared=0%, tausquared=0, p=0.8056
0.1

0.2

0.5

CVO Better

OR

95%CI

0.98
1.80
1.38
2.68
1.66
1.70
1.69

[0.04; 25.20]
[0.64; 5.03]
[0.64; 2.98]
[0.82; 8.76]
[0.84; 3.28]
[1.00; 2.91]
[0.98; 2.89]

10

MV Better

Mortality rates at longest follow-up are obtained from trials described in Table 2 comparing CVO with MV and noninfarct coronary intervention
in patients with STEMI and MV CAD. Abbreviations as in Figure 1.

fractional ow reserve (FFR) measurements to guide

The ACC/AHA/SCAI Focused Update recommendation

revascularization

3).

does not distinguish between MV primary PCI and

have

staged PCI, but rather gives 1 recommendation for MV

Additionally,

decisions
small,

(20,55,56)

randomized

(Table
trials

compared MV primary PCI with staged PCI (59,60).

PCI (15).

T A B L E 3 Randomized Controlled Trials of Staged PCI Versus CVO or MV Primary PCI

First Author (Ref. #)

Year

Design

Staged PCI
(n)

CVO
(n)

MV
(n)

Timing of
Staged PCI

Primary
Endpoint

Follow-Up
(Months)

Mortality
(n)

CV Death
(n)

MI
(n)

Revasc
(n)

Death, MI, rehosp

for ACS, revasc

30, mean

4 vs. 13

12 vs. 10

4 vs. 7

8 vs. 28

36

4 vs. 0

N/A

14* vs. 0

27 vs. 14

D, MI, non-IRA
revasc

27, mean

15 vs. 11

5 vs. 9

15 vs. 16

17 vs. 52

Staged PCI vs. CVO primary PCI

Politi (18)
2010

Randomized
Single-center
20032007

65

84

57 days, mean

Ghani (56)
2012

Randomized
single-center
20042007

80

41

<3 weeks

Engstrm (20)
2015

Randomized
Multicenter
20112014

314

313

2 days

Hlinomaz (57)
2015

Randomized
Multicenter
20092013

106

108

340 days

D, MI, stroke

38, mean

6 vs. 7

N/A

11 vs. 8

N/A

Henriques (58)
2015

Randomized
Multicenter
20082015

148

154

<7 days

LVEF, LVED

4 vs. 0

4 vs. 0

5 vs. 3

0 vs. 1

715

700

33 vs. 31

21 vs. 19

49 vs. 34

52 vs. 95

0 vs. 0

0 vs. 0

4 vs. 3

10 vs. 12

30, mean

4 vs. 6

2 vs. 4

4 vs. 2

8 vs. 6

1 vs. 0

N/A

0 vs. 3

0 vs. 2

5 vs. 6

2 vs. 4

8 vs. 8

18 vs. 20

Pooled

LVEF

Staged PCI vs. MV primary PCI

Ochala (59)
2004

Randomized
Single-center
N/A

44

48

27 days, mean

LVEF

Politi (18)
2010

Randomized
Single-center
20032007

65

65

57 days, mean

Death, MI, rehosp

for ACS, revasc

Tarasov (60)
2014

Randomized
Single-center
20112013

43

46

8 days, mean

D, MI, revasc

Pooled

152

159

*Included 5 periprocedural MI.

IRA infarct-related artery; LVED left ventricular end-diastolic diameter; LVEF left ventricular ejection fraction; N/A not available; other abbreviations as in Tables 1 and 2.

1072

Bates et al.

JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

T A B L E 4 Observational Trials of CVO Primary PCI Versus Staged PCI

First Author (Ref. #)

Year

Design

CVO
(n)

Staged PCI
(n)

Timing of
Staged PCI

Primary
Endpoint

Follow-Up
(Months)

Mortality
n (%)

Outcomes for
Staged PCI

12

CVO: 42 (12)
Staged: 12 (9.5)

MACE, MI, revasc higher

Mortality similar

13, mean

CVO: 7 (15.2)
Staged: 1 (1.5)

MACE similar
Periprocedural MI higher
Mortality lower

Corpus (38)
2004

Registry
Single-center
19982002

354

126

In-hospital

D, MI, revasc

Rigattieri (61)
2008

Retrospective
Single-center
20042006

46

64

In-hospital

D, stroke, stent
thrombosis,
Revasc,
ACS hosp

Varani (41)
2008

Registry
Single-center
20042007

156

96

In-hospital

Mortality

CVO: 10 (6.6)
Staged: 2 (2.1)

Mortality similar

Han (62)
2008

Retrospective
Single-center
N/A

149

93

715 days

Cardiac D, MI, TVR

12

CVO: 4 (2.7)
Staged: 3 (3.2)

MACE, revasc similar

Mortality similar

Hannan (53)
2010

Case-controlled
Multicenter
20032006

538

538

<60 days

Mortality

42

CVO: 40 (7.4)
Staged: 30 (5.6)

Mortality similar

Chen (63)
2010

Registry
Single-center
20022009

351

60
150

<1 month
16 months

Mortality

12

CVO: 66 (18.8)
Staged: 13 (6.2)

Mortality lower

Mohamad (42)
2011

Retrospective
Single-center
20022006

30

12

In-hospital

Mortality

12

CVO: 3 (10)
Staged: 2 (16.7)

MACE similar
Mortality similar

Barringhaus (66)
2011

Registry
Multicenter
19992007

1,345

173
130

In-hospital
Outpatient

Mortality

CVO: 106 (7.9)

Staged: 4 (2)

Periprocedural MI higher
Mortality lower

Lee (67)
2012

Registry
Multicenter
20052007

1,106

538

In-hospital

D, MI, revasc

12

CVO: 25 (2.3)
Staged: 9 (1.7)

MACE, MI, revasc similar

Mortality similar

Kim (43)
2014

Registry
Single-center
20062009

155

252

In-hospital

D, MI, revasc

36

CVO: 15 (9.7)
Staged: 11 (4.4)

MACE lower
MI, revasc similar
Mortality similar

Manari (51)
2014

Registry
Multicenter
20022010

706

988

<60 days

D, MI, TVR

24

N/A

MACE, MI lower
Revasc similar
Mortality lower

Ma (64)
2015

Registry
Single-center
20082011

246

201

7 days

D, MACE

55

CVO: 41 (16.7)
Staged: 13 (6.5)

MACE, MI, revasc lower

Mortality lower

Russo (65)
2015

Registry
Single-center
20042011

779

259

In-hospital

Mortality

CVO: 38 (5.0)
Staged: 2 (0.8)

Mortality lower

Toyota (68)
2016

Registry
Multicenter
20052007

630

681

<90 days

Mortality

60

CVO: 95 (16.0)
Staged: 59 (9.5)

MI, revasc similar

Mortality lower

hosp hospitalization; other abbreviations as in Tables 1 and 3.

CVO PRIMARY PCI VERSUS STAGED PCI. We identi-

traditional statistical methods (OR: 0.92; 95% CI: 0.40

ed 9 single-center (38,4143,6165), 4 multicenter

to 2.12) and Bayesian approaches (OR: 0.94; 95% BCI:

(51,6668), 1 case-controlled (53), and 5 randomized

0.31 to 2.09) (Figure 4).

trial (18,20,5558) reports that compared CVO primary

The DANAMI 3-PRIMULTI (Third Danish Study of

PCI versus staged PCI (Tables 3 and 4). Similar to the

Optimal Acute Treatment of Patients with STEMI:

results comparing CVO with MV primary PCI, there

Primary PCI in Multivessel Disease) trial screened

were no obvious differences in reinfarction or repeat

2,212 patients and randomized 627 patients to CVO

revascularization

primary PCI or FFR-guided staged revascularization

rates.

In

the

13 observational

studies, we observed a signicant increase in long-

before hospital discharge at 4 sites over 4 years (20).

term mortality with CVO primary PCI compared with

The sample size was calculated on the basis of an

staged PCI using traditional statistical approaches

expected annual MACE rate of 18% for CVO primary

(OR: 2.18; 95% CI: 1.58 to 3.01) and Bayesian ap-

PCI and a predicted 30% risk reduction for FFR-

proaches (OR: 2.09; 95% BCI: 1.54 to 2.88) (Figure 3).

guided staged PCI at 80% power. In the staged PCI

In 5 randomized trials, mortality rates with CVO pri-

group, 97 patients did not undergo PCI because FFR

mary PCI were no different than staged PCI using

values were >0.80, 6 were referred for coronary

JACC VOL. 68, NO. 10, 2016

Bates et al.

SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

F I G U R E 3 Forest Plot of Mortality in Observational Studies Comparing CVO Primary PCI With Staged PCI

Study

CULPRIT
Events Total

STAGED
Events Total

Odds Ratio (OR)

126
12
354
42
Corpus (2004)
64
1
46
7
Rigattieri (2008)
96
2
156
10
Varani (2008)
93
3
149
4
Han (2008)
538
30
538
40
Hannan (2010)
210
13
351
66
Chen (2010)
12
2
30
3
Mohamad (2011)
303
4
106 1345
Barringhaus (2011)
538
9
25 1106
Lee (2012)
252
11
155
15
Kim (2014)
201
13
246
41
Ma (2015)
259
2
779
38
Russo (2015)
681
59
95 630
Toyota (2016)
Bayesian hierarchical meta-analysis
161 3373
492 5885
Fixed effect model
Random effects model
Heterogeneity: Isquared=50.1%, tausquared=0.1466, p=0.02
0.1

0.2

0.5

CVO Better

OR

95%CI

1.28
11.31
3.22
0.83
1.36
3.51
0.56
6.40
1.36
2.35
2.89
6.59
1.87
2.09
2.20
2.18

[0.65; 2.52]
[1.34; 95.44]
[0.69; 15.02]
[0.18; 3.78]
[0.83; 2.22]
[1.88; 6.54]
[0.08; 3.83]
[2.34; 17.49]
[0.63; 2.93]
[1.05; 5.25]
[1.50; 5.57]
[1.58; 27.51]
[1.33; 2.64]
[1.54; 2.88]
[1.82; 2.67]
[1.58; 3.01]

10

Staged Better

Mortality rates at longest follow-up are obtained from studies described in Table 4 comparing CVO with staged coronary intervention of
noninfarct lesions in patients with STEMI and MV CAD. Staging occurred either in hospital or after hospital discharge. Abbreviations as in
Figure 1.

artery bypass graft surgery, and 19 other patients did

stroke at 38 months was not signicantly different

not undergo PCI for other reasons. The composite

(13.9% vs. 16.0%; p 0.41). The EXPLORE (Evaluating

primary outcome of all-cause mortality, reinfarction,

Xience V and Left Ventricular Function in Percuta-

and ischemia-driven revascularization at a median

neous Coronary Intervention on Occlusions After

follow-up of 27 months occurred in 40 (13%) patients

ST-Elevation Myocardial Infarction) trial randomized

who had FFR-guided staged PCI and 68 (22%) patients

302 patients with a chronic total occlusion to staged

who had CVO primary PCI (HR: 0.56; 95% CI: 0.38 to

PCI of the occluded noninfarct artery within 7 days or

0.83; p 0.004). The improvement in outcome

medical therapy (58). There were no differences in

appeared to be entirely related to a lower rate of

left ventricular ejection fraction, left ventricular end-

routine and urgent repeat revascularization. There

diastolic volume, or clinical events at 4 months.

were no differences in mortality or reinfarction rates.

The 2013 ACCF/AHA STEMI guideline recommends

Three smaller randomized controlled trials tested

PCI of a noninfarct artery before hospital discharge

CVO PCI versus staged PCI. Dambrink et al. (55,56)

only in patients with spontaneous symptoms of

randomized 120 patients to a strategy of CVO pri-

myocardial ischemia (Class I), or in patients with in-

mary PCI or FFR-guided staged PCI. There was no

termediate- or high-risk ndings on noninvasive

signicant difference in left ventricular ejection

testing (Class IIa) (11). Similarly, the 2014 ESC/EACTS

fraction measured at 6 months, nor was there a dif-

guidelines on myocardial revascularization give a

ference in the composite endpoint of mortality,

Class IIa recommendation for staged PCI for symp-

reinfarction, and repeat revascularization at 3 years

toms or ischemia within days to weeks after primary

(35.0% vs. 35.4%; p 0.96). The PRAGUE-13 (Multi-

PCI (14). The 2015 ACC/AHA/SCAI Focused Update

vessel Disease Diagnosed at the Time of PPCI for

gives a Class IIb recommendation for anatomy-based

STEMI: Complete Revascularization Versus Conser-

staged PCI (15).

vative Strategy) trial randomized 214 patients over a

4-year period to undergo CVO primary PCI or staged

MV PRIMARY PCI VERSUS STAGED PCI. We identi-

PCI at 3 to 40 days (57). The primary composite

ed 5 single-center (38,4143,69), 3 multicenter

endpoint of all-cause mortality, reinfarction, or

(51,70,71), and 3 randomized (18,59,60) trials that

1073

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JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

F I G U R E 4 Forest Plot of Mortality in Randomized Controlled Trials Comparing CVO Primary PCI With Staged PCI

CULPRIT
Events Total

Study
Politi (2010)
Ghani (2012)
Engstrom (2015)
Hinomaz (2015)
Henriques (2015)

13
0
11
7
0

84
41
313
108
154

Odds Ratio (OR)

STAGED
Events Total
4
4
15
6
4

OR

2.79 [0.87; 9.01]

0.20 [0.01; 3.90]
0.73 [0.33; 1.61]
1.16 [0.38; 3.56]
0.10 [0.01; 1.95]
0.94 [0.31; 2.09]
0.91 [0.55; 1.51]
0.92 [0.40; 2.12]

65
80
314
106
148

Bayesian hierarchical meta-analysis

Fixed effect model
31 700
33
713
Random effects model
Heterogeneity: Isquared=43.6%, tausquared=0.3606, p=0.1314
0.1

95%CI

0.2

0.5

CVO Better

10

Staged Better

Mortality rates at longest follow-up are obtained from trials described in Table 3 comparing CVO with staged coronary intervention of
noninfarct lesions in patients with STEMI and MV CAD. Staged procedures occurred 2 to 57 days after the primary intervention. Abbreviations as
in Figure 1.

compared MV primary PCI to staged PCI (Tables 3

denitive large randomized trial (Table 6). To sum-

and 5). There were no obvious differences in MACE,

marize, 6 meta-analyses showed increased mortality,

reinfarction, or repeat revascularization. In the

10 showed similar mortality, and 9 showed decreased

7 observational studies with evaluable data, we

mortality after MV PCI. Therefore, it is easy for an

observed a signicant increase in long-term mortality

author to selectively cite a meta-analysis to support a

with MV primary PCI compared with staged PCI using

conclusion or position on this topic for a publication,

both traditional statistical approaches (OR: 3.89; 95%

but our complete review of these meta-analyses il-

CI: 2.65 to 5.70) and Bayesian approaches (OR: 3.59;

lustrates the limitations of using meta-analysis as a

95% BCI: 2.04 to 5.56) (Figure 5). However, a more

primary source for evidence-based guideline recom-

critical clinical condition may have biased the selec-

mendations (15).

tion of patients for MV primary PCI, despite the Class

III proscription against that strategy. There were no
differences in the randomized trials, but the sample
sizes and event rates were quite small.

ADVANTAGES AND DISADVANTAGES OF

MV PRIMARY PCI
There are several potential advantages to performing

META-ANALYSES

MV primary PCI (Central Illustration). First, acute

optimization of myocardial blood supply may in-

Meta-analysis in the absence of an adequately pow-

crease myocardial salvage in hibernating myocardium

ered trial must be viewed as hypothesis-generating,

or watershed areas of infarction, improving left ven-

given the limitations of the assumptions required

tricular

for pooling data, as well as the limitations of the in-

conicting reports on benet (55,58,59). Second, MV

dividual studies. This is particularly true in this evi-

primary PCI may decrease the compounded risk of

dence base, with variable study populations, study

vascular complications from the repeat vascular

designs, analytical methods, and clinical endpoints. It

punctures

is widely recognized that the results of meta-analysis

Third, MV primary PCI may decrease

including

studies

length of stay and use fewer resources, increasing

frequently yield ndings that are not denitive

cost-effectiveness. Finally, complete revasculariza-

and are contradictory to

tion may decrease the risk of a future acute coronary

small

trials

or

observational

well-conducted larger

ejection

fraction,

required

multicenter randomized trials (72). The conclusions

syndrome

of 25 meta-analyses (7397) on the role of PCI in pa-

improve prognosis.

or

in

although

staged

revascularization

there

are

procedure.
hospital

procedure

and

tients with STEMI and MV CAD have been remarkably

There are several potential disadvantages to

discordant, reecting the inclusion of different trials

performing MV primary PCI (Central Illustration).

in different meta-analyses and the absence of a

First, procedure times are prolonged, and there is

JACC VOL. 68, NO. 10, 2016

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SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

1075

T A B L E 5 Observational Trials of MV Primary PCI Versus Staged PCI

First Author (Ref. #)

Year

Design

MV
(n)

Staged
(n)

Timing of
Staged PCI

Primary
Endpoint

Follow-Up
(Months)

Mortality
n (%)

Outcomes for
MV

MACE, MI, revasc higher

Mortality similar

Corpus (38)
2004

Registry
Single-center
19982002

26

126

In-hospital

D, MI, revasc

12

MV: 5 (19)
Staged: 12 (9.5)

Varani (41)
2008

Registry
Single-center
20042007

147

96

In-hospital

Mortality

MV: 15 (9.9)
Staged: 2 (2.1)

Mortality higher

Mohamad (42)
2011

Retrospective
Single-center
20022006

12

In-hospital

Mortality

12

MV: 2 (28.6)
Staged: 2 (16.7)

MACE similar
Mortality similar

Maamoun (69)
2011

Sequential
Single-center
20072008

42

36

<7 days

D, MI, ACS hosp, stroke

12

MV: 2 (4.8)
Staged: 1 (2.8)

MACE, MI, revasc similar

Mortality similar

Kornowski (70)
2011

Subset
Multicenter
20052007

275

393

30 days, mean

D, MI, revasc, stroke

12

MV: 25 (9.2)
Staged: 9 (2.3)

MACE, MI, revasc similar

Mortality higher

Jensen (71)
2012

Registry
Multicenter
20022009

354

820

<60 days

Mortality

12

MV: 36 (10.2)
Staged: 16 (2.0)

Mortality higher

Kim (43)
2014

Registry
Single-center
20062009

67

252

In-hospital

D, MI, revasc

36

MV: 5 (7.4)
Staged: 11 (4.4)

MI, revasc similar

Mortality similar

Manari (51)
2014

Registry
Multicenter
20022010

367

988

<60 days

D, MI, revasc

24

N/A

MI, revasc similar

Mortality similar

Abbreviations as in Tables 1 and 4.

increased radiation exposure. Second, higher contrast

stenosis, resolution of ST-segment elevation, nal

media volume increases the risk for contrast ne-

Thrombolysis In Myocardial Infarction (TIMI) ow,

phropathy and acute volume overload, potentially

and procedure success rates were usually omitted.

increasing hospital morbidity and mortality (98).

Neither have the indications, timing, and complete-

Third, noninfarct artery stenosis severity may be

ness of revascularization been clearly documented.

acutely exaggerated as the result of circulating

Moreover, MV primary PCI cohorts have sometimes

catecholamine-mediated vasoconstriction, and result

included

in PCI of functionally insignicant stenoses (99).

CVO primary PCI cohorts have usually included pa-

Fourth, the risk of jeopardizing remote viable

tients undergoing staged PCI, ischemia-driven PCI, or

myocardium during PCI of noninfarct artery stenoses

coronary bypass graft surgery at undocumented times.

(distal embolization, no-reow, side branch occlu-

A review of the patient enrollment dates demonstrates

sion, loss of collateral circulation) could result in

that many of the reports are older and may not reect

hemodynamic instability. Finally, there may be

improvements in clinical practice over the last

increased risk for acute and subacute stent throm-

several years. Also, prospective and retrospective,

bosis in a prothrombotic and proinammatory state.

single-center and multicenter, and observational and

patients

undergoing

staged

PCI,

and

The advantage of the staged PCI strategy is more time

randomized reports have been variably pooled in

to appropriately decide on the risks and benets of

meta-analyses, with discordant conclusions.

additional revascularization, perhaps resulting in

better patient selection (12).

Additionally, observational studies are known to

be limited by ascertainment bias, unmeasured confounders, failure to monitor or adjudicate events,

LIMITATIONS OF THE EVIDENCE BASE

and lack of adequate risk adjustment. There was

usually a large imbalance in cohort size in the

There has been signicant heterogeneity in the pub-

observational studies, with only a small proportion of

lished studies, with great variability in reporting

patients undergoing MV PCI. Conversely, the large

baseline variables, follow-up duration, and outcome

benet with MV primary PCI in the randomized trials

measures. Important patient-, operator-, and center-

most likely overestimates the true benet because

related factors have not been detailed, potentially

the trials were underpowered to detect a clinically

causing inclusion and exclusion selection bias. Data

meaningful difference in outcomes, few endpoints

on lesion location or complexity, percent diameter

occurred,

and

the

patients

were

selected

for

1076

Bates et al.

JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

F I G U R E 5 Forest Plot of Mortality in Observational Studies Comparing MV Primary PCI With Staged PCI

MULTIVESSEL
Events Total

Study

Odds Ratio (OR)

STAGED
Events Total

OR

95%CI

126
96
12
36
393
820
252

2.26 [0.72; 7.09]

5.34 [1.19; 23.9]
2.00 [0.21; 18.7]
1.75 [0.15; 20.1]
4.27 [1.96; 9.29]
5.69 [3.11; 10.4]
1.77 [0.59; 5.27]

Bayesian hierarchical meta-analysis

90
918
53 1735
Fixed effect model
Random effects model
Heterogeneity: Isquared=0%, tausquared=0, p=0.4953

3.59 [2.04; 5.56]

3.99 [2.74; 5.80]
3.89 [2.65; 5.70]

5
15
2
2
25
36
5

Corpus (2004)
Varani (2008)
Mohamad (2011)
Maamoun (2011)
Kornowski (2011)
Jensen (2012)
Kim (2014)

26
147
7
42
275
354
67

12
2
2
1
9
16
11

0.1

0.2

0.5

MV Better

10

Staged Better

Mortality rates at longest follow-up are obtained from studies in Table 5 comparing MV PCI with staged MV PCI in patients with STEMI.
Staged procedures took place during the index hospitalization or up to 60 days after the primary intervention. PCI percutaneous coronary
intervention; other abbreviations as in Figure 1.

randomization.

also

outlined, Dambrink et al. (55) and Ghani et al. (56)

limited by open-label design, premature cessation in

The

randomized

trials

are

randomized 121 patients to FFR-guided staged PCI

2 trials (16,55,56), and lack of information on clinical

or medical therapy after primary PCI and found no

or lesion selection criteria. What has really been

difference in MACE rates (55,56). Similarly, the

tested in these trials is a strategy of early invasive

DANAMI 3-PRIMULTI trial randomized 627 patients

therapy versus early noninvasive therapy for non-

after primary PCI to FFR-guided staged PCI versus

infarct artery stenoses, not 2 distinct treatments,

medical therapy and found no differences in death or

because patients frequently crossed over to the other

reinfarction rates (20). Only repeat revascularization

strategy or were lost to follow-up.

events were reduced, a preordained outcome when

noninfarct artery stenoses meeting revascularization

FRACTIONAL FLOW RESERVE

guidelines are not treated during the initial hospitalization. It may be that lesion stability and severity

It has been suggested that adding a physiological

have more prognostic value after STEMI than docu-

assessment of ischemia during coronary angiography

mentation of ischemia.

using FFR measurements might avoid the limitations

of anatomy-guided decision making and be more

FUTURE STUDIES

compatible with existing revascularization recommendations supporting documentation of ischemia

There are at least 8 randomized clinical trials in

before PCI. However, the FAME-2 (Fractional Flow

progress evaluating the role of PCI in patient with

Reserve Versus Angiography for Multivessel Evalua-

STEMI and MV CAD (Table 7). The study designs vary,

tion 2) trial found no differences in death or rein-

so complementary data will be added that will not be

farction rates with FFR-guided PCI compared with

easily aggregated by meta-analysis. Several publica-

medical therapy in 888 patients with stable CAD,

tions have suggested that the COMPLETE (Complete

despite the fact that 23% of patients had class III/IV

vs Culprit-Only Revascularization to Treat Multi-

angina, and 14% of lesions were >90% diameter ste-

vessel Disease After Primary PCI for STEMI) trial will

nosis (100). Additionally, FFR measurements may be

clarify the debate, but this trial randomized patients

increased

acutely

to CVO primary PCI versus staged PCI, not MV pri-

decreased coronary blood ow (7), although 1 report

mary PCI. Although many physicians are eager to

demonstrated good FFR reproducibility with serial

have a guideline recommendation for staged PCI, it

measurements (101). The FFR benet is also not clear

will not clarify the debate on anatomy-guided versus

as part of a staged PCI strategy. As previously

FFR-guided revascularization because FFR is only

during

primary

PCI

due

to

JACC VOL. 68, NO. 10, 2016

Bates et al.

SEPTEMBER 6, 2016:106681

PCI Strategies in Patients With STEMI and MV CAD

T A B L E 6 Meta-Analyses of CVO Primary PCI Versus MV Primary PCI or Staged PCI

First Author (Ref. #)

Year

RCT
(n)

Observational
(n)

Abstracts
(n)

Patients
(n)

Sethi (73)
2011

CVO: 27,394
MV PCI: 4,640

Mortality similar

MACE, revasc similar

Mortality similar

Navarese (74)
2011

CVO: 27,047
MV PCI: 4,118

Mortality similar

MI similar
Revasc lower
Mortality similar

Bangalore (75)
2011

10

CVO: 52,074
MV PCI: 9,690

MACE, revasc
lower
MI similar
Mortality similar

MACE, revasc lower

MI similar
Mortality lower

Vlaar (76)
2011

16

CVO: 34,295
MV PCI: 5,985

Mortality higher

Mortality higher

Takagi (77)
2011

36,689

Mortality higher

Mortality higher

Lu (78)
2013

CVO: 51,998
MV PCI: 8,240

Mortality higher

MACE, MI similar
Revasc lower
Mortality higher

Bagai (79)
2013

11

CVO: 30,492
MV PCI: 4,747

MI, revasc similar

Mortality higher

Revasc lower
Mortality higher

Bainey (80)
2014

17

CVO: 38,438
MV PCI: 7,886

Mortality similar

Revasc lower
Mortality lower

Pandit (81)
2014

CVO: 332
MV PCI: 416

Zhang (82)
2014

14

CVO: 33,594
MV PCI: 5,796

Sekercioglu (83)
2014

CVO: 324
MV PCI: 341

N/A

MI, revasc lower

Mortality lower

Dahal (84)
2014

CVO: 332
MV PCI: 573

N/A

MACE, MI, revasc lower

Mortality similar

Moretti (85)
2015

N/A

N/A

MI similar
Revasc lower
Mortality similar

Briasoulis (86)
2015

CVO: 522
MV PCI: 612

N/A

MI, revasc lower

Mortality lower

Sardar (87)
2015

CVO: 522
MV PCI: 549

N/A

MI, revasc lower

Mortality lower

Song (88)
2015

23

CVO: 36,169
MV PCI: 8,087

N/A

MACE, MI similar
Revasc lower
Mortality similar

Rasoul (89)
2015

10

CVO: 30,939
MV PCI: 5,109

N/A

MACE similar
MI, revasc lower
Mortality higher

Bangalore (90)
2015

CVO: 519
MV PCI: 646

N/A

MI similar
Revasc lower
Mortality lower

Sarathy (91)
2015

CVO: 376
MV PCI: 399

N/A

MI, revasc lower

Mortality lower

Bittl (92)
2015

14

CVO: 40,180
MV PCI: 7,588

N/A

Mortality similar

El-Hayek (93)
2015

CVO: 478
MV PCI: 566

N/A

MI, revasc lower

Mortality lower

Kowalewski (94)
2015

CVO: 666
MV PCI: 637

N/A

MI, revasc lower

Mortality similar

Elgendy (95)
2015

CVO: 939
MVI: 1,000

N/A

MACE, revasc lower

MI similar
Mortality similar

Spencer (96)
2015

CVO: 775
MV PCI: 793

N/A

MI, revasc lower

Mortality similar

Bajaj (97)
2015

CVO: 919
MV PCI: 1,054

N/A

MACE, revasc lower

MI similar
Mortality similar

F/U follow-up; RCT randomized controlled trials; other abbreviations as in Table 1.

Short-Term
MV PCI F/U

N/A
Mortality higher

Long-Term
MV PCI F/U

MI, revasc lower

Mortality lower
MI similar
Revasc lower
Mortality higher

1077

1078

Bates et al.

JACC VOL. 68, NO. 10, 2016

PCI Strategies in Patients With STEMI and MV CAD

SEPTEMBER 6, 2016:106681

CONCLUSIONS

T A B L E 7 Future Randomized Clinical Trials

Randomized
Controlled Trial

Design

Size (N)

Composite Primary Endpoint

Compared with CVO PCI, MV PCI, either at the

time of primary PCI or as a staged procedure in

COCUA
NCT01180218

CVO primary PCI vs.

MV primary PCI

646

1-yr cardiac death, STEMI,

ischemia-driven TVR

ASSIST-MI
NCT01818960

CVO primary PCI vs.

MV primary PCI

250

90-day infarct size by CMR

CULPRIT SHOCK
NCT01927549

CVO primary PCI vs.

MV primary PCI in
cardiogenic shock

706

30-day death or acute kidney

injury requiring renal
replacement therapy

superior remains to be demonstrated. Indications

FIT
NCT01160900

CVO primary PCI vs.

staged PCI

180

30-day death, MI
1-yr stent thrombosis, TVR

standards, with routine PCI of intermediate or

COMPLETE
NCT01740479

CVO primary PCI vs. staged

PCI (<72 h) with FFR for
lesions 50%70% DS

ZES for STEMI

NCT01781715

MV primary PCI vs. staged

(315 days) PCI

120

1-yr death, MI, revascularization

CompareAcute
NCT01399736

MV primary PCI with FFR vs.

ischemia-guided PCI

885

1-yr death, MI, cerebrovascular

events, revascularization

judgment to determine the optimal strategy and

CROSS-AMI
NCT01179126

Staged PCI (index

hospitalization) vs.
ischemia-guided PCI

400

1-yr cardiovascular death, MI,

revascularization, HF
hospitalization

Demonstration of myocardial ischemia, multidisci-

selected patients who are hemodynamically stable,

appears to be safe and may result in better outcomes. Whether MV primary PCI or staged PCI is

3,900

4-yr death, MI

for noninfarct artery PCI should match elective PCI

complex stenoses at time of primary PCI discouraged. Until more denitive studies are available,

ASSIST-MI Revascularization Strategies for ST Elevation Myocardial Infarction Trial; CMR cardiac magnetic
resonance; COCUA Complete Lesion Versus Culprit Lesion Revascularization; CompareAcute Comparison
Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD;
COMPLETE Complete vs Culprit-Only Revascularization to Treat Multi-vessel Disease After Primary PCI for
STEMI; CROSS-AMI Strategies of Revascularization in Patients With ST-Segment Elevation Myocardial Infarction
(STEMI) and Multivessel Disease; CULPRIT SHOCK Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic
Shock; CVO culprit-only; DS diameter stenosis; FIT Fast Infarction Treatment; FFR fractional ow reserve;
STEMI ST-segment elevation myocardial infarction; ZES for STEMI Multivessel Stenting Versus Staged
Revascularization With Zotarolimus-Eluting Stent for STEMI; other abbreviations as in Tables 1 and 2.

physicians

should

comorbidities,

integrate

lesion

clinical

complexity,

status
and

and

clinical

timing for PCI in patients with STEMI and MV CAD.

plinary evaluation by the heart team, and staged
PCI

(or

coronary

artery

bypass

graft

surgery)

following appropriate use criteria has been the

more traditional approach to pursuing MV revascularization. More studies are needed to clarify the
indications for and timing of noninfarct artery PCI,
and to determine whether MACE are more affected
by baseline characteristics than by the additional
PCI procedure.

being performed for lesions with 50% to 70% diam-

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

eter stenosis. Similarly sized randomized trials are

Eric R. Bates, CVC Cardiovascular Medicine, 1500 East

needed to compare CVO to MV primary PCI and MV

Medical Center Drive, Ann Arbor, Michigan 48109-

primary PCI to staged PCI.

5869. E-mail: ebates@umich.edu.

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