POINT/COUNTERPOINT

FRAME OF REFERENCE
Complete Immediate Revascularization of the
Patient With ST-SegmentElevation Myocardial
Infarction Is the New Standard of Care

Opposing Viewpoint, see p 1574 Keith G. Oldroyd, MB,

ChB

A
pproximately half of patients with ST-segmentelevation myocardial infarction
(STEMI) have angiographically significant multivessel disease and, in these pa-
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tients, the European (2012) and US (2013) guideline recommendations have

been that only the culprit artery should be treated acutely. In the setting of cardio-
genic shock, the guidelines recommend treating any nonculprit arteries to achieve
as complete a revascularization as possible. Both of these recommended strategies
are based on level C evidence (observational studies and consensus opinion). In the
past 4 years, there have been 3 new randomized trials that have contributed to the
knowledge base in this area (Table).
The PRAMI trial (Preventive Angioplasty in Myocardial Infarction) was a UK-based
multicenter randomized trial of culprit only percutaneous coronary intervention (PCI)
in comparison with immediate complete revascularization. On the recommendation
of the data safety and monitoring board, recruitment to the PRAMI trial was halted
in January 2013, after 465 patients had been randomly assigned. After an average
of 2 years follow-up, the relative risk reduction in the primary end point of cardiovas-
cular death, nonfatal myocardial infarction (MI), and refractory ischemia in patients
randomly assigned to complete revascularization was 65% (P<0.001), more than
double that estimated in the original power calculation. The between-group differ-
ence in the secondary end point of cardiovascular death and nonfatal MI remained
statistically significant (P<0.001).1
The CvLPRIT (Complete versus Lesion-only Primary PCI Trial) was another UK-
based multicenter randomized trial comparing the same 2 strategies as in PRAMI.
The opinions expressed in this
The observed relative risk reduction in the primary end points in patients randomly article are not necessarily those
assigned to complete revascularization was 55% (P=0.009).2 Like PRAMI, the ben- of the editors or of the American
eficial treatment effect was seen early, and, although staging was allowed in CvL- Heart Association.
PRIT, the majority of patients randomly assigned to complete revascularization had Correspondence to: Keith G.
it performed during the index procedure and even the staged patients waited only a Oldroyd, MB, ChB, Consultant
median of 1.5 days. The true treatment effect in CvLPRIT may have been underesti- Interventional Cardiologist, West
mated because, unlike PRAMI, patients were randomly assigned after angiography of Scotland Regional Heart and
Lung Centre, Golden Jubilee
but before successful culprit lesion PCI. This led to crossovers, with 11 patients
National Hospital, Agamemnon
(7%) randomly assigned to complete revascularization undergoing culprit-only PCI St, Clydebank, Glasgow G81
and 7 patients (5%) randomly assigned to culprit-only PCI undergoing complete re- 4DY, Scotland, UK. E-mail keith.
vascularization. oldroyd@nhs.net
The DANAMI-3 PRIMULTI (Third Danish Study of Optimal Acute Treatment of Pa- Key Words: coronary artery
tients with ST-Segment Elevation Myocardial Infarction - Primary PCI in Multivessel disease myocardial infarction
Disease) was a randomized trial conducted in 2 centers in Denmark and compared percutaneous coronary
culprit-only PCI with complete revascularization in patients with STEMI and multi- intervention
vessel disease. In the complete revascularization arm, all the nonculprit PCI pro- 2017 American Heart
cedures were staged, but they were performed within the index admission. The Association, Inc.

Circulation. 2017;135:15711573. DOI: 10.1161/CIRCULATIONAHA.117.025265 April 25, 2017 1571

 Oldroyd

Table. Contemporary Randomized Controlled Trials of Culprit-Only Percutaneous Coronary Intervention

Versus Complete Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for
ST-SegmentElevation Myocardial Infarction
PRAMI1 (n=465)
No. patients per center/y 19
Lesion criteria >50% DS
Strategy for nonculprit arteries Immediate percutaneous
coronary intervention
Primary end point Death/myocardial
infarction/refractory ischemia
Power calculation (80%) 20% reduced to 14%
(30% RRR)
Result 23% reduced to 9%
(65% RRR)
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CvLPRIT2 (n=296)
23
>70% DS or >50% DS in 2 views
Immediate or staged percutaneous
coronary intervention during
index admission
Death/myocardial infarction/heart
failure/ischemia-driven revascularization
37% reduced to 22%
(40% RRR)
21% reduced to 10%
(55% RRR)
DANAMI-3PRIMULTI3 (n=627)
105
50%90% DS and fractional flow
reserve 0.80 or >90% DS
Staged percutaneous coronary
intervention during index admission
(median delay 2 days)
Death/myocardial infarction/ischemia-
driven revascularization
18% reduced to 13%
(30% RRR)
22% reduced to 13%
(44% RRR)

DS indicates diameter stenosis; and RRR, relative risk reduction.

planned recruitment of 629 patients was completed and
the observed relative risk reduction in favor of complete
revascularization was 44% (P=0.004), although this was
exclusively driven by a reduction in the need for isch-
emia-driven revascularization, with no effect on mortality
or MI.3
SUMMARY
These 3 trials provide sufficient grounds to support im-
mediate complete revascularization as the new standard
of care for patients with STEMI and multivessel disease
who do not have left main coronary artery disease or
cardiogenic shock, or in whom the only nonculprit lesion
is a chronic total occlusion. Why, then, have the most
recent European and US guidelines only given this treat-
ment strategy a lukewarm class IIb recommendation?
Even in my own center, where we do >700 primary PCI
procedures per year, there is limited enthusiasm for im-
mediate complete revascularization.
Resistance to Change
I frequently hear cardiologists saying that the outcomes
in these trials do not reflect what they see in their dai-
ly practice. In other words, my anecdotal experience
trumps the randomized trials results. This is not evi-
dence-based medicine.
Undertreatment in the Culprit-Only Groups
I also frequently hear the criticism that the control
groups in all 3 trials were undertreated. Cardiologists
state that the patients randomly assigned to culprit-only
PCI should all have undergone ischemia testing and then
been revascularized if there was evidence of important
reversible ischemia. It is true that the subsequent man-
agement of the patients in these trials did not include
protocol-mandated ischemia testing, but their care was
in the hands of experienced cardiologists who could and
did manage these patients as they saw fit. Because none
of these trials was fully blinded, the clinicians knew which
patients had angiographically significant but untreated
lesions, and if they felt there was a need for ischemia
testing or further revascularization, then it was per-
formed. In any event, this criticism is based on the as-
sumption that at least 1 mechanism of benefit in these
trials was relief of ischemia in the territory of nonculprit
arteries. However, in a 200-patient substudy of CvLPRIT
using cardiovascular MRI, there was no evidence of a
difference in ischemic burden at follow-up.4 This is an
important observation, because it may also explain, in
part, the results of DANAMI-3 PRIMULTI. In this trial, un-
like PRAMI and CvLPRIT, fractional flow reserve decision
making was used to select which nonculprit stenoses
should be stented within the diameter stenosis range of
50% to 90%. This resulted in approximately one-third of
lesions (31%) that would have been stented on standard
angiographic criteria being left untreated because of
fractional flow reserve values >0.80. It should be noted
that this study failed to show any effect on mortality or
nonfatal MI. However, if in fact a major mechanism of
benefit is stabilization of nonculprit but nevertheless vul-
nerable plaques, then angiographic selection criteria (as
used in PRAMI and CvLPRIT) may be superior to fraction-
al flow reserve guidance in this setting (ongoing studies
will hopefully clarify this point).
Staging
Many cardiologists are convinced of the need for com-
plete revascularization in patients with STEMI and mul-

1572 April 25, 2017 Circulation. 2017;135:15711573. DOI: 10.1161/CIRCULATIONAHA.117.025265


tivessel disease, but prefer to undertake staged rath-
er than immediate nonculprit PCI. Often, this choice
is driven not by evidence but by local reimbursement
practices, a questionable motive for potentially compro-
mising care. Staging is clinically and economically inef-
ficient and exposes patients to a variety of avoidable
risks, including further vascular access, guide catheter
manipulation, contrast exposure, and administration of
potent antithrombotic drugs. Therefore, in an overall
health economic analysis, the immediate complete re-
vascularization strategy will always win over a staged
approach, even when the staging occurs during the
index procedure. One can speculate that the strategy
used in DANAMI-3 PRIMULTI of staging all nonculprit PCI
procedures, albeit within the index admission, may have
diluted the treatment effect. Staging beyond the index
admission seems particularly unattractive given the ear-
ly separation of the event curves in all 3 trials. Of course,
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staging may be unavoidable if other patients with STEMI
are waiting to be treated and only 1 primary PCI team is
available, but this is the exception rather than the rule in
most centers.
Complex Lesions
The operators in these trials were all experienced inter-
ventional cardiologists. Nevertheless, as can be seen
from the CONSORT charts, hundreds of patients were
excluded on the basis that their nonculprit disease was
not amenable to PCI, and I would go further and say that
the safe and efficient practice of immediate complete
revascularization requires that the nonculprit disease be
amenable to noncomplex PCI.
Conclusions
Hundreds of patients consented to participate in these
complex trials. To my mind, the results are clear and
we owe it to these patients to adopt the strategy of im-
mediate complete revascularization whenever we have a
Circulation. 2017;135:15711573. DOI: 10.1161/CIRCULATIONAHA.117.025265
Complete Immediate Revascularization
FRAME OF REFERENCE
good result in the culprit artery, and it is technically and
logistically feasible.
DISCLOSURES
None.
AFFILIATION
From West of Scotland Regional Heart and Lung Centre, Golden
Jubilee National Hospital, Glasgow, Scotland, UK.
FOOTNOTES
Circulation is available at http://circ.ahajournals.org.
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April 25, 2017 1573
 Complete Immediate Revascularization of the Patient With ST-SegmentElevation
Myocardial Infarction Is the New Standard of Care
Keith G. Oldroyd

Circulation. 2017;135:1571-1573
doi: 10.1161/CIRCULATIONAHA.117.025265
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