discussion of opening of non infarct related artery

1. Debate - opening of NON
IRA(infarct related artery)
DURING PRIMARY PCI
MODERATED BY DR. F IQBAL.
PRESENTED BY DR. S S GARDE.

2. The lesion responsible for the infarct, often referred to as the “culprit
lesion,” is readily identified and an attempt is made to re-establish blood
flow with the use of thrombectomy, balloon angioplasty, or placement of
one or more stents.
In addition to the culprit lesion(s), about 50 percent of STEMI patients have
one or more obstructive lesions remote from the area of infarction (ie, "non-
culprit" lesions).
JAMA 2014;312:2019-27.

3. IMPACT OF NON-CULPRIT LESIONS
 Patients with significant multi-vessel coronary artery disease have higher rates of mortality and
reinfarction than those with single vessel disease .
 In a study of 2082 patients undergoing primary percutaneous coronary intervention, the one-
year cumulative incidence of death for patients with single-, double-, and triple-vessel disease
was 3.2, 4.4, and 7.8 percent (p = 0.003), and of target vessel revascularization was 11.3,
15.2, and 16.2 percent (p = 0.02), respectively.
 The adverse impact of multi-vessel disease due to non-culprit lesions raises the question as to
whether revascularization of these non-culprit lesions will improve outcomes.
J Am Coll Cardiol 2005; 45:1397.

4. THEORY OF NON CULPRIT ARTERY
 In theory, one might argue that this is because the lesion in the non-infarct artery
is an "innocent bystander" and therefore should be approached in much the same
way one approaches stable ischemic heart disease.
 Opponents to this argument might propose that these non-culprit lesions may also
be biologically active, (studies have shown that there are often multiple complex
plaques in patients with acute myocardial infarction [MI], and therefore these
arteries warrant treatment in much the same way one would approach any
unstable lesion.

5. There are four principal strategies to manage non-culprit lesions:
 Refer for coronary artery bypass surgery (CABG) after the patient has recovered from the acute
STEMI. After primary PCI, there will be some patients who have a relatively clear indication for
CABG. For example, a patient with a right coronary artery STEMI who is found to have a significant
left main stenosis.
 No further revascularization, unless standard indications for revascularization in patients with stable
coronary artery disease are met.
 PCI of non-culprit lesions at the time of primary PCI.
 PCI of non-culprit lesions prior to hospital discharge = STAGED PROCEDURE.

6. TRIALS – debating against the MV PCI
 In 2010 the NEW YORK STATE experience reported lower in hospital mortality for culprit vessel alone
PCI compared to MV PCI during the index procedure in patients without hemodynamic compromise,
low EF or malignant arrhythmia.
 In This study patient undergoing staged PCI to the non IRA vessel within 60 days after the index
procedure had significantly lower 12 month mortality rate than those having culprit artery PCI alone.
 2011, Kornowski et al. Analyzed the results of THE HORIZON AMI trial and showed that MV-PCI at
the time of index procedure for STEMI was associated with a higher 1 year mortality(9.2 vs 2.3 %) and
MACE (18.1 vs 13.4%)compared to a staged procedure for the non IRA PCI.

7. TRIALS
BANGALORE et al - in a large meta analysis showed REDUCTION
in the need for repeat PCI in the MV PCI group, reported no significant
difference at 30 day in mortality, stroke, and TVR.
VLAAR et al - reported 60 % higher risk of long term mortality with
MV PCI when compared to culprit only PCI alone and also the staging
of non IRA PCI was associated with reduction of mortality.

8. TRIALS –
Observational studies, performed prior to the randomized trials and
their meta-analyses , concluded that culprit-only PCI, as opposed to
multivessel PCI, at the time of initial reperfusion led to better
outcomes.
However, when patients who were treated with staged PCI during the
hospitalization were analyzed separately, short- and long-term
outcomes favoured multi-vessel revascularization compared with
culprit only strategy.
J Am Coll Cardiol 2011; 58:692.

9. TRIALS - FAVOURING MV PCI
DANAMI-3—PRIMULTI, PRAMI, CvLPRIT, and Compare Acute
being the four largest RCTs, have compared culprit only with
complete revascularization.

10. The PRAMI trial
 The PRAMI trial planned to randomly assign 600 patients to either preventive or no
preventive PCI after successful primary PCI .
 Preventive PCI was defined as immediate (same-setting) PCI of non-infarct arteries with
>50 percent diameter stenosis (staged procedures were discouraged).
 FFR assessment was not used.

11.  Patients with cardiogenic shock or prior CABG were excluded.
 The trial was terminated early by the data and safety monitoring committee after the enrollment of 465 patients for
the finding of a highly significant between-group difference in the incidence of the primary outcome (a composite
of cardiac death, nonfatal MI, or refractory angina) favoring non-culprit PCI (9 versus 23 percent; HR 0.35, 95%
CI 0.21-0.58) during a mean follow-up of 23 months.
 The HRs for the individual components of the composite end point all favored non-culprit PCI.
 However, we believe there are limitations to PRAMI, including stopping early, liberal definition of multivessel
disease, and a small number of events.

12. The CvLPRIT trial
 The CvLPRIT trial randomly assigned 296 patients to complete revascularization during
the hospitalization or infarct-related, artery-only revascularization .
 Multivessel disease was defined as one or more non-culprit stenosis of >70 percent
diameter stenosis in other coronary arteries.
 Among those assigned to treatment prior to discharge, 64 percent received complete
revascularization at the time of primary PCI.

13.  FFR assessment was not used.
 The primary composite end point (all-cause death, recurrent MI, heart failure, and
ischemia -driven revascularization at 12 months) occurred less often in the complete
revascularization group (10.0 versus 21.2 percent; HR 0.45, 95% CI 0.24-0.84).
 All components of the primary end point were lower with complete revascularization
and there was no difference in the safety end points (major bleeding, contrast-induced
nephropathy, or stroke).

14.  The results from the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus
Multivessel PCI in Cardiogenic Shock) trial were reported at the Transcatheter
Cardiovascular Therapeutics Congress 2017.
This international, multicenter, open-label trial of 706 patients with acute MI
compared a strategy of culprit-only revascularization in patients with acute MI
complicated by cardiogenic shock with a strategy of multi-vessel PCI performed
at the time of primary PCI.

15.  Approximately two thirds of enrolled patients had STEMI. It is important to note
that patients with CTO were included in this trial, and multi-vessel PCI of these
CTO performed at the time of primary PCI was encouraged for those patients
assigned to multi-vessel PCI performed at the time of primary PCI.
 Additionally, an ischemia-guided or FFR-guided approach to PCI of the non-
culprit artery was encouraged in the group of patients assigned to culprit-only
revascularization.

16.  At 30 days, the composite primary end point of death or renal-replacement therapy had occurred
in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341
patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI],
0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared
with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of
renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07).
 CONCLUSION:- Among patients who had multivessel coronary artery disease and acute
myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe
renal failure leading to renal-replacement therapy was lower among those who initially underwent
PCI of the culprit lesion only than among those who underwent immediate multivessel PCI.

17. DANAMI-3—PRIMULTI
 DANAMI-3—PRIMULTI randomly assigned 313 patients with one or more clinically
significantly coronary stenoses in addition to the culprit lesion to either no further invasive
treatment or complete, FFR-guided revascularization before discharge, usually two days
after initial PCI.
 The primary composite end point (all-cause mortality, non-fatal infarction, and ischemia-
driven revascularization of lesions in non-infarct related arteries) occurred less often in the
group with complete revascularization (13 versus 22 percent; hazard ratio [HR] 0.56, 95%
CI 0.38-0.83).

18.  The benefit was almost entirely attributable to a lower rate of subsequent
revascularization of non-infarct related arteries (HR 0.31, 95% CI 0.18-0.53).
 Approximately one-third of patients who were assigned to the complete
revascularization strategy did not undergo non-culprit PCI, as FFR values were
above the discrimination value of 0.80 despite the fact that initial angiography
suggested high-grade stenoses.

19. The Compare-Acute trial
 The Compare-Acute trial randomly assigned 885 patients in a 1:2 ratio to undergo
complete revascularization of non-infarct related coronary arteries or no revascularization .
 FFR was performed in both groups and, in the revascularization group, PCI was performed
in all lesions with a result ≤0.80.
 In most cases, revascularization took place during the index procedure.

20. The primary composite end point of death from any cause, nonfatal MI,
revascularization, and cerebrovascular events at 12 months occurred less
often in the complete revascularization group (7.8 versus 20.5 percent;
hazard ratio 0.22, 95% CI 0.22-0.55).
This outcome was driven principally by many fewer revascularizations
being performed in the complete revascularization group (18 versus
103). In addition, there was a trend toward a lower rate of MI (2.4 versus
4.7 percent) with complete revascularization.

22. Eur Heart J 2012; 33:768
 A 2017 network meta-analysis of 10 randomized trials with 2285 patients compared four
revascularization strategies in STEMI patients with multivessel disease at the time of primary
PCI: complete revascularization at the index procedure;
 complete revascularization as a staged procedure, with the non-culprit vessel(s) being treated
prior to discharge;
 complete revascularization as a staged procedure in which the non-culprit vessel(s) was treated
within a few weeks after discharge (not symptom driven);
 and culprit only PCI .

23. This meta-analysis was published before Compare-Acute. The
following findings were noted at a median follow-up of 25 months:
 Complete revascularization, either at the index procedure or as a staged procedure, compared with culprit only
PCI, was associated with a lower risk of major adverse cardiac events (risk ratio [RR] 0.57, 95% CI 0.42-0.77).
 Most studies used a composite of all-cause mortality, recurrent MI, and ischemia driven revascularization.
 The composite primary end point (major adverse cardiovascular events) was driven principally by a lower rate of
urgent revascularization (RR 0.44, 95% CI 0.30-0.66).
 There were trends toward lower risks of all-cause mortality and recurrent MI (RR 0.76, 95% CI 0.52-1.12 and
0.55, 95% CI 0.23-1.28, respectively).

24.  17.7% of patients assigned to the culprit-only group underwent staged PCI of the
non-culprit lesions.
 The primary endpoint, a composite of death or renal replacement therapy at 30
days, was significantly lower in the group of patients assigned to culprit-only
revascularization (45.9 vs. 55.4%; RR 0.83; 95% CI, 0.71-0.96; p = 0.01).
 Mortality was also significantly lower with culprit-only revascularization (RR
0.84; 95% CI, 0.72-0.98; p = 0.03), and there was a trend toward a lower rate of
renal replacement therapy with culprit-only revascularization (RR 0.71; 95% CI,
0.49-1.03; p = 0.07).

25.  Not long ago, the American College of Cardiology and American Heart
Association guidelines for the management of STEMI recommended against PCI
of the non-culprit artery at the time of primary PCI.
 This recommendation was based on a large body of evidence from observational
studies that reported a worse outcome with multi-vessel PCI performed at the
time of primary PCI.
J Am Coll Cardiol 2013;61:485-510.
J Am Coll Cardiol 2011;58(7):692-703

26.  More recently, however, several randomized controlled trials (RCT) WHICH HAVE
BEEN DISCUSSED PREVIOUSLY have demonstrated a favorable outcome with
multi-vessel PCI in stable patients with STEMI.
 Based on some of these trials, a revised Class IIB recommendation was given for
considering PCI of the non-infarct artery in selected patients with STEMI and MVD,
either at the time of primary PCI or as a planned staged procedure.(2016)
J Am Coll Cardiol 2016;67:1235-50.

27. Staged Multi-Vessel PCI
The contemporary randomized trials that specifically examined a strategy
of staged multi-vessel PCI include DANAMI-3-PRIMULTI and the
PRAGUE-13 trial.

28.  In DANAMI-3-PRIMULTI, 627 patients were randomized at 4 PCI centers to staged multi-vessel PCI (with FFR
guidance for lesions that had stenoses of 50-90%) or culprit-only revascularization (with no planned invasive
treatment of the non-culprit artery).
 Compared with culprit-only revascularization, staged multi-vessel FFR-guided PCI was associated with a
significantly lower rate of the composite primary outcome death, non-fatal MI, or ischemia-driven
revascularization (13 vs. 22%; HR 0.56; 95% CI, 0.38-0.83; p = 0.004).
 The favorable results from FFR-guided staged multi-vessel PCI were entirely driven by a lower rate of ischemia-
driven revascularization in the staged multi-vessel PCI arm, with no notable difference in the rates of death or non-
fatal MI between the two treatment strategies.

29.  The PRAGUE-13 trial did not report a benefit from staged multi-vessel PCI
compared with culprit-only revascularization.
 In this trial of 217 patients enrolled at 6 centers, the primary endpoint, a
composite of death, non-fatal MI, and stroke, occurred in 16% of the patients
treated with staged multi-vessel PCI and 13.9% of patients assigned to culprit-
only revascularization (HR 1.35; 95% CI, 0.66-2.74; p = 0.407)

30. Timing of Multi-Vessel PCI
 Although multi-vessel PCI performed at the time of primary PCI may offer the
advantage of a one-setting procedure and reduced hospital costs.
 staging the PCI may allow additional time to assess the clinical importance of the
non-infarct vessel and evaluate for associated comorbidities.
 multi-vessel PCI performed at the time of primary PCI was associated with a
greater improvement in left ventricular (LV) function. J Invasive Cardiol 2004;16:699-702.

31. Compared with culprit-only revascularization, there was a
similar reduction in cardiovascular outcomes with any of the
multi-vessel PCI strategies:
Multi-vessel PCI performed at the time of primary PCI: relative risk
(RR) 0.37; 95% CI, 0.24-0.59; p < 0.01
Staged in-hospital multi-vessel PCI: RR 0.49; 95% CI, 0.27-0.91; p =
0.02
Staged multi-vessel PCI after hospital discharge: RR 0.58; 0.35-0.98;
p = 0.04
JACC Cardiovasc Interv 2017;10:315-24.

32. HYPOTHESIS BEHIND PRE AND POST
PRAMI ERA
 EUROPEAN myocardial revascularization collaboration suggest a potential mortality benefit
as well should persuade the interventionist to think differently about in favour of hypothesis
that an acute coronary syndrome can destabilize remote plaques as well. (non infarct related
artery might be having a vulnerable plaque).
 Vulnerable plaque is not always more than 50 % and in PRAMI trial lesions less than 50 %
WERE NOT PACIFIED.

33. It might be radical to start placing stents in every =/>50% stenosis or more
as preventive strategy based on experience of 200 trial patients.
So , FFR might play important role here in decision making.

34. Multi vessel PCI in cardiogenic shock
 Multi-vessel PCI performed at the time of primary PCI in patients with cardiogenic
shock and MVD is generally considered an acceptable management strategy despite
the limited data supporting this approach.
 most of the RCT of MVD in STEMI excluded patients with shock, and
observational studies of STEMI patients with cardiogenic shock and MVD have
reported mixed results, with worse, similar, and better outcomes when multi-vessel
PCI performed at the time of primary PCI is employed

35. On the other hand, a meta-analysis of all of the observational
studies reported a worse short-term outcome with multi-
vessel PCI performed at the time of primary PCI in
cardiogenic shock.
J Am Coll Cardiol 2016; 67:1235

36. An Algorithm for the Management of STEMI
Patients With MVD
the trial results support a strategy of non-infarct artery PCI (either at the time of
the primary PCI or as a staged procedure) as the initial approach to treating
STEMI patients with MVD who are free of cardiogenic shock.
The studies of routine PCI in stable patients with MVD all demonstrated safety
with multi-vessel PCI without any excess rates of stroke, bleeding, or contrast-
induced nephropathy.

38. Culprit artery-only PCI versus multi-vessel PCI;
ACC RECOMMENDATIONS
 The 2013 recommendation was Class III (Harm), indicating that PCI should not
be performed in a non-infarct artery at the time of primary PCI in patients with
STEMI who are haemodynamically stable (Level of Evidence B).
 The new recommendation of 2015 is now Class IIb, demonstrating that PCI of a
non-infarct artery may be considered in selected patients with STEMI and multi-
vessel disease who are haemodynamically stable, either at the time of primary
PCI or as a planned staged procedure (Level of Evidence B-R).

39. ESC
 CLASS IIa recommendation for PCI to the non infarct related lesion in the
concerned setting.

40. What is the optimal timing?
 For patients who will undergo PCI of non-culprit lesions, the optimal timing is
not known.
 Factors to consider for performing non-culprit PCI at the time of primary PCI
include patient stability, ability to accurately assess lesion significance in the
setting of acute coronary syndromes, likelihood of procedural success, risk of the
intervention (eg, possibility of increased risk of contrast nephropathy), and the
potential benefit of revascularization (eg, size of the ischemic territory).

41. Which non-culprit lesions?
 Non-culprit lesions should be treated during the initial hospitalization if
angiographic or intracoronary imaging suggests unstable morphology (ulceration,
thrombus) or in patients with recurrent ischemic symptoms.
 In the absence of unprovoked ischemia, PCI of non-culprit lesions should be
treated soon after PCI if the stenosis severity is >70 percent, or >50 percent with
an abnormal fractional flow reserve (FFR), and the location of the lesion is
proximal or in a vessel that subtends a significant area of myocardium.

42. If the burden of ischemia is unclear or the viability of the territory is
in question, further assessment with noninvasive imaging prior to PCI
can be considered.
Vessels not suitable for stenting, due to small diameter or distal
location, should not be treated routinely.

43. Chronic total occlusions
 The optimal approach to STEMI patients with chronic total occlusion (CTO) of a
non-culprit lesion, identified at the time of primary PCI, is not known.
 To perform PCI of non-culprit CTO in STEMI patients if the occluded vessel
subtends a significant area of potentially viable myocardium and the anatomic
complexity predicts a high likelihood of success with an antegrade approach or
the procedure can be performed by an operator proficient in more advanced
chronic total occlusion techniques, including re-entry and retrograde approaches,
such that the risks of the procedure are low.

44.  Up to 15 percent of patients with STEMI are found to have CTO of a non-culprit artery at
coronary angiography. The presence of an occlusion of another epicardial artery significantly
increases mortality and this is particularly true if CTO is present .
 The EXPLORE trial randomly assigned 204 STEMI patients to PCI of CTO within seven days
of primary PCI or no PCI . At four months, there was no difference in the primary end points of
the mean left ventricular ejection fraction (44.1 versus 44.8 percent) and left ventricular end
diastolic volume (215.6 versus 212.8 mL), both assessed by cardiac magnetic resonance
imaging.
Eur Heart J. 2012 Mar;33(6):768-75. Epub 2012 Jan 12.
Am J Cardiol. 2010 Apr;105(7):955-9. Epub 2010 Feb 13.

45. Who should receive FFR ?
 To perform measurement of FFR for non-culprit lesions of intermediate or
indeterminate severity seen at the time of angiography. Such lesions that meet
criteria for “significant,” such as a values <0.80, are associated with provocable
ischemia with an accuracy >90 percent and should be considered for
revascularization.