PCI Strategies in Patients With ST-Segment Elevation ... · REVIEW TOPIC OF THE WEEK PCI Strategies in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary

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REVIEW TOPIC OF THE WEEK

PCI Strategies in Patients WithST-Segment Elevation MyocardialInfarction and MultivesselCoronary Artery Disease
Eric R. Bates, MD,a Jacqueline E. Tamis-Holland, MD,b John A. Bittl, MD,c Patrick T. O’Gara, MD,d
Glenn N. Levine, MDe

ABSTRACT

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Recent randomized controlled trials have suggested that patients with ST-segment elevation myocardial infarction and

multivessel coronary artery disease may benefit 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 limi-

tations, and establish a base for future studies. (J Am Coll Cardiol 2016;68:1066–81)

© 2016 by the American College of Cardiology Foundation.

A pproximately 50% of patients with ST-segment elevation myocardial infarction(STEMI) have multivessel (MV) coronary ar-

tery disease (CAD) (1). The short-term prognosis afterSTEMI is worse with MV CAD than with single-vesselCAD (2–4), perhaps because of additional plaqueinstability (5,6); impaired myocardial perfusioncaused by endothelial dysfunction, microvascularspasm, or inflammation (7); or decreased contractilityin noninfarct zones (2,8). The long-term prognosis isalso worse because of older age, more atheroscleroticrisk factors, higher atherosclerotic disease burden,and lower left ventricular ejection fraction in patientswith MV CAD (9).

The 2011 American College of Cardiology Founda-tion (ACCF)/American Heart Association (AHA)/Society for Cardiac Angiography and Interventions

m the aDivision of Cardiovascular Diseases, Department of Internal Me

bor, Michigan; bDivision of Cardiology, Department of Internal Medicine, M

unroe Heart and Vascular Institute, Munroe Regional Medical Center, Oca

ernal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts;

dical Center, Baylor College of Medicine, Houston, Texas. The authors ha

the contents of this paper to disclose.

nuscript received March 3, 2016; revised manuscript received April 19, 20

(SCAI) guideline for percutaneous coronary inter-vention (PCI) and the 2013 ACCF/AHA guideline forSTEMI recommended that primary PCI should not beperformed (Class III, Harm) in a noninfarct artery inpatients with STEMI who are hemodynamically stable(10,11). Additionally, the American College of Cardi-ology (ACC) Appropriate Use Criteria Task Forcelabeled PCI of a noninfarct artery at the time ofprimary PCI as “inappropriate” (12). These recom-mendations arose from historical safety concernsthat included an increased potential for proceduralcomplications, contrast nephropathy, and stentthrombosis. However, more complete acute revascu-larization in patients with STEMI may be safer in thecurrent era due to advances in stent technology andantiplatelet therapy; might decrease mortality, rein-farction, and repeat revascularization rates; and

dicine, University of Michigan Medical Center, Ann

ount Sinai St. Luke’s Hospital, New York, New York;

la, Florida; dCardiovascular Division, Department of

and the eSection of Cardiology, Michael E. DeBakey

ve reported that they have no relationships relevant

16, accepted May 10, 2016.

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

AB BR E V I A T I O N S

AND ACRONYM S

ACC = American College of

Cardiology

ACCF = American College of

Cardiology Foundation

AHA = American Heart

Association

BCI = Bayesian confidence

interval

CAD = coronary artery disease

CI = confidence interval

CVO = culprit-vessel only

ESC = European Society of

Cardiology

FFR = fractional flow reserve

MACE = major adverse

cardiovascular event(s)

MV = multivessel

OR = odds ratio

PCI = percutaneous coronary

intervention

SCAI = Society for

Cardiovascular Angiography

and Interventions

STEMI = ST-segment elevation

myocardial infarction

J A C C V O L . 6 8 , N O . 1 0 , 2 0 1 6 Bates et al.S E P T E M B E R 6 , 2 0 1 6 : 1 0 6 6 – 8 1 PCI Strategies in Patients With STEMI and MV CAD

1067

could reduce hospital length of stay, resource utili-zation, and cost. In fact, several recent randomizedcontrolled trials and meta-analyses have supportedthis strategy (see later discussion). In response tothese reports, the ACC removed the 2012 proscriptionagainst MV primary PCI from the American Board ofInternal Medicine Foundation Choosing WiselyCampaign in 2014 (13). Additionally, the 2014 Euro-pean Society of Cardiology (ESC)/European Associa-tion for Cardio-Thoracic Surgery (EACTS) Guidelineson Myocardial Revascularization and the 2015 ACC/AHA/SCAI Focused Update on Primary PCI committeeassigned a new Class IIb recommendation,concluding that MV primary PCI may be considered inselected hemodynamically stable patients with sig-nificant noninfarct artery stenoses (14,15).

Nevertheless, the best strategy for the treatment ofthe noninfarct artery in patients with STEMI and MVCAD remains an unresolved issue, with importantimplications for potentially improving clinical out-comes in these patients. PCI strategies include: 1)culprit vessel-only (CVO) primary PCI with continuedmedical management and PCI of noninfarct arteriesonly for spontaneous angina or myocardial ischemiaon stress testing; 2) MV PCI at the time of primary PCI;or 3) CVO primary PCI, followed by staged PCI ofnoninfarct arteries later during the index hospitali-zation or soon after hospital discharge (CentralIllustration). This review summarizes the data on PCIfor patients with STEMI and MV CAD (15).

The terms preventive angioplasty (16) and completerevascularization (17–20) have previously been usedto describe what we are presently naming MV primaryPCI and staged PCI. We prefer these terms becausethe term preventive has traditionally been used todescribe noninvasive interventions that attempt toprevent invasive interventions or major adversecardiovascular events (MACE), and because completerevascularization was not routinely attempted in pa-tients with chronic total occlusions, other complexlesions, or smaller arteries.

METHODS

A search of the published reports was performed us-ing the PubMed database through December 2015. Weincluded in our analysis previously published reportsthat were cited in previous publications andany additional studies that were independentlyidentified. When possible, we excluded patients withnon–ST-segment elevation myocardial infarction,hemodynamic instability, prior fibrinolytic therapy,and prior coronary artery bypass surgery. We docu-mented study design and enrollment periods,

primary endpoints, and quantitative mortal-ity results; and separated MV primary PCI andstaged PCI results. Qualitative results forMACE, reinfarction, and repeat revasculari-zation were tabulated because the studieswere too heterogeneous to permit an accuratequantitative analysis. Twelve reports wereexcluded from this analysis: 4 included pa-tients with non–ST-segment elevation acutecoronary syndromes (21–24); 3 did not sepa-rate MV primary PCI from staged PCI (25–27);2 compared complete versus incompleterevascularization (28,29); 2 studied patientswith heart failure and cardiogenic shock(30,31); and 1 compared MV primary PCI withsingle-vessel primary PCI (32).

To illustrate the relative effectiveness ofCVO versus MV PCI, we used conventionalstatistical methods to create forest plots toillustrate differences in mortality rates, arelevant endpoint reported in all trialscomparing primary PCI strategies in patientswith STEMI and MV CAD. We applied arandom effects model to acknowledge thevariation in study design, treatment dura-tion, and length of follow-up among thestudies. For inductive inference and to
emulate the random effects model, we used hierar-chical Bayesian meta-analysis. In the absence ofstrong evidence for the superiority of 1 strategy overanother, we used noninformative priors defined by atreatment effect of 0.00 and precision of 0.0001 toensure that the posterior inference would be domi-nated by the likelihood of the data (33,34). All ana-lyses were intention-to-treat. Standard meta-analysiswas performed using the open-source statistical pro-gram R 3.0.2 and the library package meta 3.8-0 (35).Bayesian computations were run with the open-source program OpenBUGS 3.2.3 (Open BayesianInference Using Gibbs Sampling), using Markov chainMonte Carlo modeling (34,36), linked to R with BRugs(37).
CVO VERSUS MV PRIMARY PCI. We identified 6single-center (38–43), 8 multicenter (44–51), and 3case-controlled (52–54) observational reports thatcompared CVO versus MV primary PCI (Table 1). Ingeneral, in the current era with new-generation stentimplantation and dual antiplatelet therapy, thereappeared to be no increased risk for reinfarction whenasymptomatic periprocedural myocardial biomarkerelevations were not counted as events. The risk forrepeat revascularization was inconsistently lowerwith MV primary PCI in these studies, but was never

CENTRAL ILLUSTRATION PCI Strategies in Patients With STEMI and MV Disease: CVO Primary PCI Versus MV PCI

Strategies

Initial procedure

Days−weeks later

Culprit vessel-only primary PCI

Culprit vessel-only PCI Culprit vessel PCIand non-culprit vessel PCI

Non-culprit vessel PCIfor spontaneous ischemia

or intermediate/high risk findingson noninvasive testing

Non-culprit vessel PCI

Culprit vessel-only PCI

Multivessel primary PCI Staged PCI

Pros

Reduced contrast volumeReduced risk of

PCI complications

Decreased repeatrevascularization

Decreased hospital length of stay

Time to assess benefit vs. riskof non-culprit vessel PCI

Increased repeatrevascularization risk

Potential reduction in LV recovery

Prolonged procedure timeIncreased contrast volume

Increased periprocedural MI riskPotentially unnecessary PCI of

functionally insignificant stenosis

Additional PCI access riskAdditional procedure costsCons

Bates, E.R. et al. J Am Coll Cardiol. 2016;68(10):1066–81.

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 vessel–only (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 dis-

advantages of each strategy are illustrated. LV ¼ left ventricular.

Bates et al. J A C C V O L . 6 8 , N O . 1 0 , 2 0 1 6

PCI Strategies in Patients With STEMI and MV CAD S E P T E M B E R 6 , 2 0 1 6 : 1 0 6 6 – 8 1

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contrasted with the total number of additional non-infarct artery PCI procedures performed initiallyto obtain that result. We observed a nonsignificantreduction in long-term mortality with CVO comparedwith MV primary PCI using both traditional statisticalapproaches (odds ratio [OR]: 0.83; 95% confidenceinterval [CI]: 0.62 to 1.09) and Bayesian approaches(posterior median OR: 0.83; 95% Bayesian confidenceinterval [BCI]: 0.59 to 1.15) (Figure 1).

Four randomized trials (16–19) compared CVO toMV primary PCI (Table 2). MACE, reinfarction, andrepeat revascularization rates were lower with MVprimary PCI. We observed a nonsignificant increasein long-term mortality with CVO compared with MVprimary PCI using both traditional statistical ap-proaches (OR: 1.69; 95% CI: 0.98 to 2.89) and Bayesianapproaches (OR: 1.66; 95% BCI: 0.84 to 3.28)(Figure 2).

The HELP-AMI (Hepacoat for Culprit or MultivesselStenting for Acute Myocardial Infarction) trial ran-domized 69 patients in a 3:1 ratio to MV or CVO pri-mary PCI (17). There was a nonsignificant reductionin repeat revascularization with MV primary PCI

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

Politi et al. (18) randomized 214 patients to CVOprimary PCI, MV primary PCI, or staged PCI. Again,repeat revascularization rates were lower with MVprimary PCI, but there were no differences in death orreinfarction rates.

The PRAMI (Preventive Angioplasty in AcuteMyocardial Infarction) trial screened 1,922 patientsand enrolled 465 patients at 5 sites over 5 years (16).Recruitment was stopped prematurely by the datasafety and monitoring board with a mean follow-up of23 months due to significant differences betweengroups. The sample size was on the basis of an ex-pected annual MACE rate of 20% for CVO primary PCIand a 30% risk reduction for MV primary PCI at 80%power. Thirteen patients did not receive assignedtherapy, and 18 were lost to follow-up. The compositeprimary outcome of cardiac death, nonfatal reinfarc-tion, or refractory angina occurred in 21 (9%) patientstreated with MV primary PCI compared with 53 (22%)patients treated with CVO primary PCI (hazard ratio[HR]: 0.35; 95% CI: 0.21 to 0.58; p < 0.001). There

TABLE 1 Observational Trials of CVO Versus MV Primary PCI

First Author (Ref. #)Year Design CVO MV

PrimaryEndpoint

Follow-Up(Months)

Mortality,n (%)

Outcomes forMV

Roe (52)2001

Case-controlledMulticenter1995–1999

61 68 D, MI, revasc 6 CVO: 10 (16)MV: 17 (25)

MACE, MI, revasc similarMortality similar

Corpus (38)2004

RegistrySingle-center1998–2002

354 26 D, MI, revasc 12 CVO: 42 (12)MV: 5 (19)


Khattab (39)2008

Sequential cohortSingle-center2004–2005

45 28 D, MI, revasc 12 CVO: 3 (7)MV: 2 (8)


Qarawani (40)2008

RetrospectiveSingle-center2001–2004

25 95 D, MI, CHF, ischemia 12 CVO: 2 (8)MV: 9 (9.4)

MACE, MI, revasc lowerMortality similar

Varani (41)2008


156 147 Mortality 1 CVO: 10 (6.6)MV: 15 (9.9)

Mortality similar

Cavender (44)2009

RegistryMulticenter2004–2007

23,146 2,701 Mortality In-hospital CVO: 586 (2.5)MV: 88 (3.3)

MACE similarMortality similar*

Hannan (53)2010


458 458 Mortality 42 CVO: 31 (6.7)MV: 48 (10.4)

Mortality similar

Toma (45)2010

SubgroupMulticenter2004–2007

1,984 217 Mortality 3 CVO: 111 (5.6)MV: 27 (12.5)

Mortality higher

Dziewierz (46)2010


707 70 Mortality 12 CVO: 57 (8.1)MV: 11 (15.7)

Mortality similar*

Mohamad (42)2011


30 7 Mortality 12 CVO: 3 (10)MV: 2 (28.6)

MACE similarMortality similar

Bauer (47)2013


2,118 419 Mortality In-hospital CVO: 72 (3.4)MV: 6 (1.4)

MI higherMortality similar*

Jaguszewski (48)2013


3,833 1,108 Mortality In-hospital CVO: 68 (4.4)MV: 81 (7.3)

MI similarMortality similar*

Santos (49)2014


180 77 Mortality In-hospital CVO: 14 (7.8)MV: 2 (2.6)

MI similarMortality similar*

Jeger (50)2014


1,467 442 Mortality 12 CVO: 40 (2.7)MV: 12 (2.7)

MI similarRevasc lowerMortality similar

Kim (43)2014


155 67 D, MI, revasc 36 CVO: 15 (9.7)MV: 5 (7.4)


Manari (51)2014


706 367 D, MI, TVR 24 CVO: 127 (18.0)MV: 26 (7.1)

MI, MACE lowerRevasc similarMortality lower

Iqbal (54)2014


2,418 403 Mortality 12 CVO: 164 (6.8)MV: 41 (10.2)

MACE (in-hospital) higherMortality higher*

*Adjusted mortality rates.

CHF ¼ congestive heart failure; CVO ¼ culprit vessel-only; D ¼ death; MACE ¼ major adverse cardiovascular events; MI ¼ myocardial infarction; MV ¼ multivessel; PCI ¼percutaneous coronary intervention; revasc ¼ repeat revascularization; TVR ¼ target vessel revascularization.


1069

were statistically significant reductions in the com-posite of death and myocardial infarction, and in re-fractory angina and repeat revascularization rates infavor of MV primary PCI.

The CvLPRIT (Complete Versus Culprit-LesionOnly Primary PCI) trial screened 850 patients andenrolled 296 patients at 7 sites over 2 years (19).The sample size was calculated on the basis of an

expected MACE rate of 37% for CVO primary PCI and22% for MV PCI at 80% power. Eighteen patientscrossed over, and 19 were lost to follow-up. MV pri-mary PCI was performed in 97 patients, and stagedPCI was performed in 42 patients. The compositeprimary outcome of all-cause death, reinfarction,heart failure, and ischemia-driven revascularizationat 12 months occurred in 15 (10%) patients with

FIGURE 1 Forest Plot of Mortality in Observational Studies Comparing CVO With MV Primary PCI

Study

Fixed effect modelRandom effects modelHeterogeneity: I−squared=76.6%, tau−squared=0.1929, p<0.0001

Roe (2001)Corpus (2004)Qarawani (2008)Khattab (2008)Varani (2008)Cavender (2009)Hannan (2010)Toma (2010)Dziewierz (2010)Mohamad (2011)Bauer (2013)Jaguszewski (2013)Santos (2014)Jeger (2014)Kim (2014)Manari (2014)Iqbal (2014)

Events

2214

13 42 2 3 8

1321 54 111 57 3

72 168 14

40 15

127 164

Total

40562

79 354 25 45 156

25802 503

1984 707 30

2118 3833 180 1467 155

706 2418

CULPRIT MULTIVESSELEvents

565

19 5 9 2 12

246 59 27 11 2 6 81 2 12 5

26 41

Total

7189

79 26 95 28 147

3134 503 217 70 7

4191108

77 442 67

367 403

0.1 0.2 0.5 1 5 10

Odds Ratio (OR)

CVO Better

OR

0.750.83

0.620.570.830.930.610.630.910.420.470.282.420.583.161.001.332.880.64

95%−CI

[0.67; 0.82][0.62; 1.09]

[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]

Bayesian hierarchical meta-analysis 0.83 [0.59; 1.15]

2MV Better

Mortality rates at longest follow-up are obtained from the studies described in Table 1 comparing culprit vessel–only (CVO) to multivessel (MV)

coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) and MV coronary artery disease (CAD). CI ¼ con-

fidence interval.



1070

MV PCI compared with 31 (21%) patients with CVOprimary PCI (HR: 0.45; 95% CI: 0.24 to 0.84;p ¼ 0.009). There were no statistically significantdifferences in death, reinfarction, heart failure, orrepeat revascularization rates, although the trendsfavored MV PCI.

TABLE 2 Randomized Controlled Trials of CVO Versus MV Primary PC

First Author (Ref. #)Year Design

CVO(n)

MV(n)

PrimaryEndpoint

Di Mario (17)2004

Randomizedmulticenter2004

17 52 Revasc

Politi (18)2010

Randomizedsingle-center2003–2007

84 65* Death, MI, rehosfor ACS, reva

Wald (16)2013

Randomizedmulticenter2008–2013

231 234 CV death,MI,refractory an

Gershlick (19)2015

Randomizedmulticenter2011–2013

146 150† Death, MI, HF, re

Pooled 478 501

*Excludes 65 patients randomized to staged PCI. †Includes 42 patients who underwent

ACS ¼ acute coronary syndrome; CV ¼ cardiovascular; HF ¼ heart failure; rehosp ¼ r

It should be noted that 2 of the randomized trialsthat tested CVO versus MV primary PCI includedpatients with staged PCI (18,19), with the resultsoften included as MV primary PCI in meta-analyses.Four other randomized trials have tested CVO pri-mary PCI versus staged PCI (20,55–58), with 2 using

I

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

psc

30, mean 13 vs. 6 10 vs. 4 7 vs. 2 28 vs. 6

gina

23, mean 16 vs. 12 10 vs. 4 20 vs. 7 46 vs. 16

vasc 12 10 vs. 4 7 vs. 2 4 vs. 2 16 vs. 8

39 vs. 23 27 vs. 11 32 vs. 12 96 vs. 39

staged PCI.

ehospitalization; other abbreviations as in Table 1.

FIGURE 2 Forest Plot of Mortality in Randomized Controlled Trials Comparing CVO With MV Primary PCI

Study

Fixed effect modelRandom effects modelHeterogeneity: I−squared=0%, tau−squared=0, p=0.8056

Di Mario (2004)Politi (2010)Wald (2013)Gershlick (2014)

Events

39

0131610

Total

478

17 84231146

CULPRITEvents

23

1 612 4

Total

501

52 65

234150

0.1 0.2 0.5 1 5 10

Odds Ratio (OR)

CVO Better

OR

1.701.69

0.981.801.382.68

95%−CI

[1.00; 2.91][0.98; 2.89]

[0.04; 25.20][0.64; 5.03][0.64; 2.98][0.82; 8.76]

Bayesian hierarchical meta-analysis 1.66

MULTIVESSEL

[0.84; 3.28]

2MV 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.


1071

fractional flow reserve (FFR) measurements to guiderevascularization decisions (20,55,56) (Table 3).Additionally, 2 small, randomized trials havecompared MV primary PCI with staged PCI (59,60).

TABLE 3 Randomized Controlled Trials of Staged PCI Versus CVO or


Staged PCI(n)

CVO(n)

MV(n)

TiSta

Staged PCI vs. CVO primary PCI

Politi (18)2010

RandomizedSingle-center2003–2007

65 84 — 57 d

Ghani (56)2012

Randomizedsingle-center2004–2007

80 41 — <3

Engstrøm (20)2015

RandomizedMulticenter2011–2014

314 313 — 2

Hlinomaz (57)2015


106 108 — 3–4

Henriques (58)2015


148 154 — <

Pooled 715 700

Staged PCI vs. MV primary PCI

Ochala (59)2004

RandomizedSingle-centerN/A

44 — 48 27 d

Politi (18)2010


65 — 65 57 d

Tarasov (60)2014


43 — 46 8 da

Pooled 152 159

*Included 5 periprocedural MI.

IRA ¼ infarct-related artery; LVED ¼ left ventricular end-diastolic diameter; LVEF ¼ l

The ACC/AHA/SCAI Focused Update recommendationdoes not distinguish between MV primary PCI andstaged PCI, but rather gives 1 recommendation for MVPCI (15).

MV Primary PCI

ming ofged PCI

PrimaryEndpoint

Follow-Up(Months)

Mortality(n)

CV Death(n)

MI(n)

Revasc(n)

ays, mean Death, MI, rehospfor ACS, revasc

30, mean 4 vs. 13 12 vs. 10 4 vs. 7 8 vs. 28

weeks LVEF 36 4 vs. 0 N/A 14* vs. 0 27 vs. 14

days D, MI, non-IRArevasc

27, mean 15 vs. 11 5 vs. 9 15 vs. 16 17 vs. 52

0 days D, MI, stroke 38, mean 6 vs. 7 N/A 11 vs. 8 N/A

7 days LVEF, LVED 4 4 vs. 0 4 vs. 0 5 vs. 3 0 vs. 1

33 vs. 31 21 vs. 19 49 vs. 34 52 vs. 95

ays, mean LVEF 6 0 vs. 0 0 vs. 0 4 vs. 3 10 vs. 12

ays, mean Death, MI, rehospfor ACS, revasc

30, mean 4 vs. 6 2 vs. 4 4 vs. 2 8 vs. 6

ys, mean D, MI, revasc 6 1 vs. 0 N/A 0 vs. 3 0 vs. 2

5 vs. 6 2 vs. 4 8 vs. 8 18 vs. 20

eft ventricular ejection fraction; N/A ¼ not available; other abbreviations as in Tables 1 and 2.

TABLE 4 Observational Trials of CVO Primary PCI Versus Staged PCI


CVO(n)

Staged PCI(n)

Timing ofStaged PCI

PrimaryEndpoint

Follow-Up(Months)

Mortalityn (%)

Outcomes forStaged PCI

Corpus (38)2004


354 126 In-hospital D, MI, revasc 12 CVO: 42 (12)Staged: 12 (9.5)

MACE, MI, revasc higherMortality similar

Rigattieri (61)2008


46 64 In-hospital D, stroke, stentthrombosis,

Revasc,ACS hosp

13, mean CVO: 7 (15.2)Staged: 1 (1.5)

MACE similarPeriprocedural MI higherMortality lower

Varani (41)2008


156 96 In-hospital Mortality 1 CVO: 10 (6.6)Staged: 2 (2.1)

Mortality similar

Han (62)2008

RetrospectiveSingle-centerN/A

149 93 7–15 days Cardiac D, MI, TVR 12 CVO: 4 (2.7)Staged: 3 (3.2)

MACE, revasc similarMortality similar

Hannan (53)2010


538 538 <60 days Mortality 42 CVO: 40 (7.4)Staged: 30 (5.6)

Mortality similar

Chen (63)2010


351 60150

<1 month1–6 months

Mortality 12 CVO: 66 (18.8)Staged: 13 (6.2)

Mortality lower

Mohamad (42)2011


30 12 In-hospital Mortality 12 CVO: 3 (10)Staged: 2 (16.7)


Barringhaus (66)2011


1,345 173130

In-hospitalOutpatient

Mortality 6 CVO: 106 (7.9)Staged: 4 (2)

Periprocedural MI higherMortality lower

Lee (67)2012


1,106 538 In-hospital D, MI, revasc 12 CVO: 25 (2.3)Staged: 9 (1.7)


Kim (43)2014


155 252 In-hospital D, MI, revasc 36 CVO: 15 (9.7)Staged: 11 (4.4)

MACE lowerMI, revasc similarMortality similar

Manari (51)2014


706 988 <60 days D, MI, TVR 24 N/A MACE, MI lowerRevasc similarMortality lower

Ma (64)2015


246 201 7 days D, MACE 55 CVO: 41 (16.7)Staged: 13 (6.5)

MACE, MI, revasc lowerMortality lower

Russo (65)2015


779 259 In-hospital Mortality 6 CVO: 38 (5.0)Staged: 2 (0.8)

Mortality lower

Toyota (68)2016


630 681 <90 days Mortality 60 CVO: 95 (16.0)Staged: 59 (9.5)

MI, revasc similarMortality lower

hosp ¼ hospitalization; other abbreviations as in Tables 1 and 3.



1072

CVO PRIMARY PCI VERSUS STAGED PCI. We identi-fied 9 single-center (38,41–43,61–65), 4 multicenter(51,66–68), 1 case-controlled (53), and 5 randomizedtrial (18,20,55–58) reports that compared CVO primaryPCI versus staged PCI (Tables 3 and 4). Similar to theresults comparing CVO with MV primary PCI, therewere no obvious differences in reinfarction or repeatrevascularization rates. In the 13 observationalstudies, we observed a significant increase in long-term mortality with CVO primary PCI compared withstaged PCI using traditional statistical approaches(OR: 2.18; 95% CI: 1.58 to 3.01) and Bayesian ap-proaches (OR: 2.09; 95% BCI: 1.54 to 2.88) (Figure 3).In 5 randomized trials, mortality rates with CVO pri-mary PCI were no different than staged PCI using

traditional statistical methods (OR: 0.92; 95% CI: 0.40to 2.12) and Bayesian approaches (OR: 0.94; 95% BCI:0.31 to 2.09) (Figure 4).

The DANAMI 3-PRIMULTI (Third Danish Study ofOptimal Acute Treatment of Patients with STEMI:Primary PCI in Multivessel Disease) trial screened2,212 patients and randomized 627 patients to CVOprimary PCI or FFR-guided staged revascularizationbefore hospital discharge at 4 sites over 4 years (20).The sample size was calculated on the basis of anexpected annual MACE rate of 18% for CVO primaryPCI and a predicted 30% risk reduction for FFR-guided staged PCI at 80% power. In the staged PCIgroup, 97 patients did not undergo PCI because FFRvalues were >0.80, 6 were referred for coronary

FIGURE 3 Forest Plot of Mortality in Observational Studies Comparing CVO Primary PCI With Staged PCI

Study

Fixed effect modelRandom effects modelHeterogeneity: I−squared=50.1%, tau−squared=0.1466, p=0.02

Corpus (2004)Rigattieri (2008)Varani (2008)Han (2008)Hannan (2010)Chen (2010)Mohamad (2011)Barringhaus (2011)Lee (2012)Kim (2014)Ma (2015)Russo (2015)Toyota (2016)

Events

492

42 7

10 4

40 66 3

106 25 15 41 38 95

Total

5885

354 46 156 149 538 351 30

13451106 155

246 779 630

CULPRIT STAGEDEvents

161

12 1 2 3

30 13 2 4 9 11 13 2

59

Total

3373

126 64 96 93

538 210 12

303 538 252 201 259 681

0.1 0.2 0.5 1 5 10

Odds Ratio (OR)

CVO Better Staged Better

OR

2.20 2.18

1.2811.31 3.22 0.83 1.36 3.51 0.56 6.40 1.36 2.35 2.89 6.59 1.87

95%−CI

[1.82; 2.67][1.58; 3.01]

[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]


2

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.


1073

artery bypass graft surgery, and 19 other patients didnot undergo PCI for other reasons. The compositeprimary outcome of all-cause mortality, reinfarction,and ischemia-driven revascularization at a medianfollow-up of 27 months occurred in 40 (13%) patientswho had FFR-guided staged PCI and 68 (22%) patientswho had CVO primary PCI (HR: 0.56; 95% CI: 0.38 to0.83; p ¼ 0.004). The improvement in outcomeappeared to be entirely related to a lower rate ofroutine and urgent repeat revascularization. Therewere no differences in mortality or reinfarction rates.

Three smaller randomized controlled trials testedCVO PCI versus staged PCI. Dambrink et al. (55,56)randomized 120 patients to a strategy of CVO pri-mary PCI or FFR-guided staged PCI. There was nosignificant difference in left ventricular ejectionfraction measured at 6 months, nor was there a dif-ference in the composite endpoint of mortality,reinfarction, and repeat revascularization at 3 years(35.0% vs. 35.4%; p ¼ 0.96). The PRAGUE-13 (Multi-vessel Disease Diagnosed at the Time of PPCI forSTEMI: Complete Revascularization Versus Conser-vative Strategy) trial randomized 214 patients over a4-year period to undergo CVO primary PCI or stagedPCI at 3 to 40 days (57). The primary compositeendpoint of all-cause mortality, reinfarction, or

stroke at 38 months was not significantly different(13.9% vs. 16.0%; p ¼ 0.41). The EXPLORE (EvaluatingXience V and Left Ventricular Function in Percuta-neous Coronary Intervention on Occlusions AfterST-Elevation Myocardial Infarction) trial randomized302 patients with a chronic total occlusion to stagedPCI of the occluded noninfarct artery within 7 days ormedical therapy (58). There were no differences inleft ventricular ejection fraction, left ventricular end-diastolic volume, or clinical events at 4 months.

The 2013 ACCF/AHA STEMI guideline recommendsPCI of a noninfarct artery before hospital dischargeonly in patients with spontaneous symptoms ofmyocardial ischemia (Class I), or in patients with in-termediate- or high-risk findings on noninvasivetesting (Class IIa) (11). Similarly, the 2014 ESC/EACTSguidelines on myocardial revascularization give aClass IIa recommendation for staged PCI for symp-toms or ischemia within days to weeks after primaryPCI (14). The 2015 ACC/AHA/SCAI Focused Updategives a Class IIb recommendation for anatomy-basedstaged PCI (15).

MV PRIMARY PCI VERSUS STAGED PCI. We identi-fied 5 single-center (38,41–43,69), 3 multicenter(51,70,71), and 3 randomized (18,59,60) trials that

FIGURE 4 Forest Plot of Mortality in Randomized Controlled Trials Comparing CVO Primary PCI With Staged PCI

Study

Fixed effect modelRandom effects modelHeterogeneity: I−squared=43.6%, tau−squared=0.3606, p=0.1314

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

Events

31

13 011 7 0

Total

700

84 41313108154

CULPRITEvents

33

4 415 6 4

Total

713

65 80314106148

STAGED

0.1 0.2 0.5 10

Odds Ratio (OR)

CVO Better Staged Better

OR

0.910.92

2.790.200.731.160.10

95%−CI

[0.55; 1.51][0.40; 2.12]

[0.87; 9.01][0.01; 3.90][0.33; 1.61][0.38; 3.56][0.01; 1.95]


1 2 5

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.



1074

compared MV primary PCI to staged PCI (Tables 3and 5). There were no obvious differences in MACE,reinfarction, or repeat revascularization. In the7 observational studies with evaluable data, weobserved a significant increase in long-term mortalitywith MV primary PCI compared with staged PCI usingboth traditional statistical approaches (OR: 3.89; 95%CI: 2.65 to 5.70) and Bayesian approaches (OR: 3.59;95% BCI: 2.04 to 5.56) (Figure 5). However, a morecritical clinical condition may have biased the selec-tion of patients for MV primary PCI, despite the ClassIII proscription against that strategy. There were nodifferences in the randomized trials, but the samplesizes and event rates were quite small.

META-ANALYSES

Meta-analysis in the absence of an adequately pow-ered trial must be viewed as hypothesis-generating,given the limitations of the assumptions requiredfor pooling data, as well as the limitations of the in-dividual studies. This is particularly true in this evi-dence base, with variable study populations, studydesigns, analytical methods, and clinical endpoints. Itis widely recognized that the results of meta-analysisincluding small trials or observational studiesfrequently yield findings that are not definitiveand are contradictory to well-conducted largermulticenter randomized trials (72). The conclusionsof 25 meta-analyses (73–97) on the role of PCI in pa-tients with STEMI and MV CAD have been remarkablydiscordant, reflecting the inclusion of different trialsin different meta-analyses and the absence of a

definitive large randomized trial (Table 6). To sum-marize, 6 meta-analyses showed increased mortality,10 showed similar mortality, and 9 showed decreasedmortality after MV PCI. Therefore, it is easy for anauthor to selectively cite a meta-analysis to support aconclusion or position on this topic for a publication,but our complete review of these meta-analyses il-lustrates the limitations of using meta-analysis as aprimary source for evidence-based guideline recom-mendations (15).

ADVANTAGES AND DISADVANTAGES OF

MV PRIMARY PCI

There are several potential advantages to performingMV primary PCI (Central Illustration). First, acuteoptimization of myocardial blood supply may in-crease myocardial salvage in hibernating myocardiumor watershed areas of infarction, improving left ven-tricular ejection fraction, although there areconflicting reports on benefit (55,58,59). Second, MVprimary PCI may decrease the compounded risk ofvascular complications from the repeat vascularpunctures required in a staged procedure.Third, MV primary PCI may decrease hospitallength of stay and use fewer resources, increasingcost-effectiveness. Finally, complete revasculariza-tion may decrease the risk of a future acute coronarysyndrome or revascularization procedure andimprove prognosis.

There are several potential disadvantages toperforming MV primary PCI (Central Illustration).First, procedure times are prolonged, and there is

TABLE 5 Observational Trials of MV Primary PCI Versus Staged PCI


MV(n)

Staged(n)

Timing ofStaged PCI

PrimaryEndpoint

Follow-Up(Months)

Mortalityn (%)

Outcomes forMV

Corpus (38)2004


26 126 In-hospital D, MI, revasc 12 MV: 5 (19)Staged: 12 (9.5)

MACE, MI, revasc higherMortality similar

Varani (41)2008


147 96 In-hospital Mortality 1 MV: 15 (9.9)Staged: 2 (2.1)

Mortality higher

Mohamad (42)2011


7 12 In-hospital Mortality 12 MV: 2 (28.6)Staged: 2 (16.7)


Maamoun (69)2011

SequentialSingle-center2007–2008

42 36 <7 days D, MI, ACS hosp, stroke 12 MV: 2 (4.8)Staged: 1 (2.8)


Kornowski (70)2011

SubsetMulticenter2005–2007

275 393 30 days, mean D, MI, revasc, stroke 12 MV: 25 (9.2)Staged: 9 (2.3)

MACE, MI, revasc similarMortality higher

Jensen (71)2012


354 820 <60 days Mortality 12 MV: 36 (10.2)Staged: 16 (2.0)

Mortality higher

Kim (43)2014


67 252 In-hospital D, MI, revasc 36 MV: 5 (7.4)Staged: 11 (4.4)

MI, revasc similarMortality similar

Manari (51)2014


367 988 <60 days D, MI, revasc 24 N/A MI, revasc similarMortality similar

Abbreviations as in Tables 1 and 4.


1075

increased radiation exposure. Second, higher contrastmedia volume increases the risk for contrast ne-phropathy and acute volume overload, potentiallyincreasing hospital morbidity and mortality (98).Third, noninfarct artery stenosis severity may beacutely exaggerated as the result of circulatingcatecholamine-mediated vasoconstriction, and resultin PCI of functionally insignificant stenoses (99).Fourth, the risk of jeopardizing remote viablemyocardium during PCI of noninfarct artery stenoses(distal embolization, no-reflow, side branch occlu-sion, loss of collateral circulation) could result inhemodynamic instability. Finally, there may beincreased risk for acute and subacute stent throm-bosis in a prothrombotic and proinflammatory state.The advantage of the staged PCI strategy is more timeto appropriately decide on the risks and benefits ofadditional revascularization, perhaps resulting inbetter patient selection (12).

LIMITATIONS OF THE EVIDENCE BASE

There has been significant heterogeneity in the pub-lished studies, with great variability in reportingbaseline variables, follow-up duration, and outcomemeasures. Important patient-, operator-, and center-related factors have not been detailed, potentiallycausing inclusion and exclusion selection bias. Dataon lesion location or complexity, percent diameter

stenosis, resolution of ST-segment elevation, finalThrombolysis In Myocardial Infarction (TIMI) flow,and procedure success rates were usually omitted.Neither have the indications, timing, and complete-ness of revascularization been clearly documented.Moreover, MV primary PCI cohorts have sometimesincluded patients undergoing staged PCI, andCVO primary PCI cohorts have usually included pa-tients undergoing staged PCI, ischemia-driven PCI, orcoronary bypass graft surgery at undocumented times.A review of the patient enrollment dates demonstratesthat many of the reports are older and may not reflectimprovements in clinical practice over the lastseveral years. Also, prospective and retrospective,single-center and multicenter, and observational andrandomized reports have been variably pooled inmeta-analyses, with discordant conclusions.

Additionally, observational studies are known tobe limited by ascertainment bias, unmeasured con-founders, failure to monitor or adjudicate events,and lack of adequate risk adjustment. There wasusually a large imbalance in cohort size in theobservational studies, with only a small proportion ofpatients undergoing MV PCI. Conversely, the largebenefit with MV primary PCI in the randomized trialsmost likely overestimates the true benefit becausethe trials were underpowered to detect a clinicallymeaningful difference in outcomes, few endpointsoccurred, and the patients were selected for

FIGURE 5 Forest Plot of Mortality in Observational Studies Comparing MV Primary PCI With Staged PCI

Study

Fixed effect modelRandom effects modelHeterogeneity: I−squared=0%, tau−squared=0, p=0.4953

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

Events

90

515 2 2

2536 5

Total

918

26147

7 42275354 67

MULTIVESSELEvents

53

12 2 2 1 91611

Total

1735

126 96 12 36

393 820 252

STAGED Odds Ratio (OR)

MV Better

OR

3.993.89

2.265.342.001.754.275.691.77

95%−CI

[2.74; 5.80][2.65; 5.70]

[0.72; 7.09] [1.19; 23.9] [0.21; 18.7] [0.15; 20.1][1.96; 9.29] [3.11; 10.4][0.59; 5.27]


0.1 0.2 0.5 101 2 5Staged 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 ¼ percutaneous coronary

intervention; other abbreviations as in Figure 1.



1076

randomization. The randomized trials are alsolimited by open-label design, premature cessation in2 trials (16,55,56), and lack of information on clinicalor lesion selection criteria. What has really beentested in these trials is a strategy of early invasivetherapy versus early noninvasive therapy for non-infarct artery stenoses, not 2 distinct treatments,because patients frequently crossed over to the otherstrategy or were lost to follow-up.

FRACTIONAL FLOW RESERVE

It has been suggested that adding a physiologicalassessment of ischemia during coronary angiographyusing FFR measurements might avoid the limitationsof anatomy-guided decision making and be morecompatible with existing revascularization recom-mendations supporting documentation of ischemiabefore PCI. However, the FAME-2 (Fractional FlowReserve Versus Angiography for Multivessel Evalua-tion 2) trial found no differences in death or rein-farction rates with FFR-guided PCI compared withmedical therapy in 888 patients with stable CAD,despite the fact that 23% of patients had class III/IVangina, and 14% of lesions were >90% diameter ste-nosis (100). Additionally, FFR measurements may beincreased during primary PCI due to acutelydecreased coronary blood flow (7), although 1 reportdemonstrated good FFR reproducibility with serialmeasurements (101). The FFR benefit is also not clearas part of a staged PCI strategy. As previously

outlined, Dambrink et al. (55) and Ghani et al. (56)randomized 121 patients to FFR-guided staged PCIor medical therapy after primary PCI and found nodifference in MACE rates (55,56). Similarly, theDANAMI 3-PRIMULTI trial randomized 627 patientsafter primary PCI to FFR-guided staged PCI versusmedical therapy and found no differences in death orreinfarction rates (20). Only repeat revascularizationevents were reduced, a preordained outcome whennoninfarct artery stenoses meeting revascularizationguidelines are not treated during the initial hospi-talization. It may be that lesion stability and severityhave more prognostic value after STEMI than docu-mentation of ischemia.

FUTURE STUDIES

There are at least 8 randomized clinical trials inprogress evaluating the role of PCI in patient withSTEMI and MV CAD (Table 7). The study designs vary,so complementary data will be added that will not beeasily aggregated by meta-analysis. Several publica-tions have suggested that the COMPLETE (Completevs Culprit-Only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI) trial willclarify the debate, but this trial randomized patientsto CVO primary PCI versus staged PCI, not MV pri-mary PCI. Although many physicians are eager tohave a guideline recommendation for staged PCI, itwill not clarify the debate on anatomy-guided versusFFR-guided revascularization because FFR is only

TABLE 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)

Short-TermMV PCI F/U

Long-TermMV PCI F/U

Sethi (73)2011

2 9 0 CVO: 27,394MV PCI: 4,640

Mortality similar MACE, revasc similarMortality similar

Navarese (74)2011

2 8 0 CVO: 27,047MV PCI: 4,118

Mortality similar MI similarRevasc lowerMortality similar

Bangalore (75)2011

2 10 7 CVO: 52,074MV PCI: 9,690

MACE, revasclower

MI similarMortality similar

MACE, revasc lowerMI similarMortality lower

Vlaar (76)2011

2 16 0 CVO: 34,295MV PCI: 5,985

Mortality higher Mortality higher

Takagi (77)2011

4 7 0 36,689 Mortality higher Mortality higher

Lu (78)2013

3 8 2 CVO: 51,998MV PCI: 8,240

Mortality higher MACE, MI similarRevasc lowerMortality higher

Bagai (79)2013

3 11 0 CVO: 30,492MV PCI: 4,747

MI, revasc similarMortality higher

Revasc lowerMortality higher

Bainey (80)2014

3 17 6 CVO: 38,438MV PCI: 7,886

Mortality similar Revasc lowerMortality lower

Pandit (81)2014

3 0 0 CVO: 332MV PCI: 416

N/A MI, revasc lowerMortality lower

Zhang (82)2014

4 14 0 CVO: 33,594MV PCI: 5,796

Mortality higher MI similarRevasc lowerMortality higher

Sekercioglu (83)2014

3 0 0 CVO: 324MV PCI: 341


Dahal (84)2014

4 0 0 CVO: 332MV PCI: 573

N/A MACE, MI, revasc lowerMortality similar

Moretti (85)2015

4 9 0 N/A N/A MI similarRevasc lowerMortality similar

Briasoulis (86)2015

5 0 0 CVO: 522MV PCI: 612


Sardar (87)2015

5 0 0 CVO: 522MV PCI: 549


Song (88)2015

7 23 0 CVO: 36,169MV PCI: 8,087

N/A MACE, MI similarRevasc lowerMortality similar

Rasoul (89)2015

5 10 0 CVO: 30,939MV PCI: 5,109

N/A MACE similarMI, revasc lowerMortality higher

Bangalore (90)2015

5 0 0 CVO: 519MV PCI: 646

N/A MI similarRevasc lowerMortality lower

Sarathy (91)2015

4 0 0 CVO: 376MV PCI: 399


Bittl (92)2015

4 14 0 CVO: 40,180MV PCI: 7,588

N/A Mortality similar

El-Hayek (93)2015

4 0 0 CVO: 478MV PCI: 566


Kowalewski (94)2015

7 0 0 CVO: 666MV PCI: 637

N/A MI, revasc lowerMortality similar

Elgendy (95)2015

7 0 0 CVO: 939MVI: 1,000

N/A MACE, revasc lowerMI similarMortality similar

Spencer (96)2015

5 0 0 CVO: 775MV PCI: 793

N/A MI, revasc lowerMortality similar

Bajaj (97)2015

8 0 0 CVO: 919MV PCI: 1,054

N/A MACE, revasc lowerMI similarMortality similar

F/U ¼ follow-up; RCT ¼ randomized controlled trials; other abbreviations as in Table 1.


1077

TABLE 7 Future Randomized Clinical Trials

RandomizedControlled Trial Design Size (N) Composite Primary Endpoint

COCUANCT01180218

CVO primary PCI vs.MV primary PCI

646 1-yr cardiac death, STEMI,ischemia-driven TVR

ASSIST-MINCT01818960

CVO primary PCI vs.MV primary PCI

250 90-day infarct size by CMR

CULPRIT SHOCKNCT01927549

CVO primary PCI vs.MV primary PCI incardiogenic shock

706 30-day death or acute kidneyinjury requiring renalreplacement therapy

FITNCT01160900

CVO primary PCI vs.staged PCI

180 30-day death, MI1-yr stent thrombosis, TVR

COMPLETENCT01740479

CVO primary PCI vs. stagedPCI (<72 h) with FFR forlesions 50%–70% DS

3,900 4-yr death, MI

ZES for STEMINCT01781715

MV primary PCI vs. staged(3–15 days) PCI

120 1-yr death, MI, revascularization

CompareAcuteNCT01399736

MV primary PCI with FFR vs.ischemia-guided PCI

885 1-yr death, MI, cerebrovascularevents, revascularization

CROSS-AMINCT01179126

Staged PCI (indexhospitalization) vs.ischemia-guided PCI

400 1-yr cardiovascular death, MI,revascularization, HFhospitalization

ASSIST-MI ¼ Revascularization Strategies for ST Elevation Myocardial Infarction Trial; CMR ¼ cardiac magneticresonance; COCUA ¼ Complete Lesion Versus Culprit Lesion Revascularization; CompareAcute ¼ ComparisonBetween FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD;COMPLETE ¼ Complete vs Culprit-Only Revascularization to Treat Multi-vessel Disease After Primary PCI forSTEMI; CROSS-AMI¼ Strategies of Revascularization in Patients With ST-Segment Elevation Myocardial Infarction(STEMI) and Multivessel Disease; CULPRIT SHOCK ¼ Culprit Lesion Only PCI Versus Multivessel PCI in CardiogenicShock; CVO¼ culprit-only; DS¼ diameter stenosis; FIT¼ Fast Infarction Treatment; FFR¼ fractional flow reserve;STEMI ¼ ST-segment elevation myocardial infarction; ZES for STEMI ¼ Multivessel Stenting Versus StagedRevascularization With Zotarolimus-Eluting Stent for STEMI; other abbreviations as in Tables 1 and 2.



1078

being performed for lesions with 50% to 70% diam-eter stenosis. Similarly sized randomized trials areneeded to compare CVO to MV primary PCI and MVprimary PCI to staged PCI.

CONCLUSIONS

Compared with CVO PCI, MV PCI, either at thetime of primary PCI or as a staged procedure inselected patients who are hemodynamically stable,appears to be safe and may result in better out-comes. Whether MV primary PCI or staged PCI issuperior remains to be demonstrated. Indicationsfor noninfarct artery PCI should match elective PCIstandards, with routine PCI of intermediate orcomplex stenoses at time of primary PCI discour-aged. Until more definitive studies are available,physicians should integrate clinical status andcomorbidities, lesion complexity, and clinicaljudgment to determine the optimal strategy andtiming for PCI in patients with STEMI and MV CAD.Demonstration of myocardial ischemia, multidisci-plinary evaluation by the heart team, and stagedPCI (or coronary artery bypass graft surgery)following appropriate use criteria has been themore traditional approach to pursuing MV revas-cularization. More studies are needed to clarify theindications for and timing of noninfarct artery PCI,and to determine whether MACE are more affectedby baseline characteristics than by the additionalPCI procedure.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Eric R. Bates, CVC Cardiovascular Medicine, 1500 EastMedical Center Drive, Ann Arbor, Michigan 48109-5869. E-mail: [email protected].

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