The PRAMI trial was a randomized controlled trial that compared preventive percutaneous coronary intervention (PCI) to PCI limited to the infarct artery in patients with ST-segment elevation myocardial infarction (STEMI) and multi-vessel coronary artery disease. The trial found that preventive PCI of non-infarct arteries with major stenoses significantly reduced the risk of adverse cardiovascular events compared to PCI limited to the infarct artery alone. However, the trial had a small sample size. Guidelines recommend PCI of a non-infarct artery be performed separately from primary PCI, but the optimal timing remains unclear due to varying results from observational studies.

1. PRAMI Trial
Abdelkader Almanfi, MD, MRCP-UK
Texas Heart Institute
Journal club
11/04/2013

2. Disclosure
I have nothing to disclose except that I am getting free
lunches, books, dinners and courses from countless number of
companies.
But for sure, No cash money or checks involved (yet)

3. Original Article
Randomized Trial of Preventive Angioplasty
in Myocardial Infarction
David S. Wald, M.D., Joan K. Morris, Ph.D., Nicholas J. Wald, F.R.S., Alexander J.
Chase, M.B., B.S., Ph.D., Richard J. Edwards, M.D., Liam O. Hughes, M.D., Colin
Berry, M.B., Ch.B., Ph.D., Keith G. Oldroyd, M.D., for the PRAMI Investigators
N Engl J Med
Volume 369(12):1115-1123
September 19, 2013

4. Study Overview
• Patients with acute STEMI were randomly assigned
to undergo infarct-vessel-only PCI or preventive
PCI (PCI to noninfarct arteries with stenoses).
• The rate of the primary outcome of cardiac
death, myocardial infarction, or refractory angina
was lower with preventive PCI.

5. Enrollment and Follow-up.
Wald DS et al. N Engl J Med 2013;369:1115-1123

6. Kaplan–Meier Curves for the Primary Outcome.
Wald DS et al. N Engl J Med 2013;369:1115-1123

7. Characteristics of the Patients at Baseline.
Wald DS et al. N Engl J Med 2013;369:1115-1123

8. Details Regarding PCI and Medical Therapy at Discharge.
Wald DS et al. N Engl J Med 2013;369:1115-1123

9. Prespecified Clinical Outcomes.
Wald DS et al. N Engl J Med 2013;369:1115-1123

10. Conclusions
• In patients with STEMI and multi-vessel
coronary artery disease undergoing infarctartery PCI, preventive PCI in non-infarct
coronary arteries with major stenoses
significantly reduced the risk of adverse
cardiovascular events, as compared with PCI
limited to the infarct artery.

11. Critics about the study:
- Sample size is small
-Larger number of patients were inferior infarcts
- EF was not reported in the study

12. What does the guidelines say about PCI in
STEMI and how the question of noninfarct artery
PCI was addressed in 2013 guidelines ?

13. Primary PCI in STEMI
I
IIa
IIb
III
Primary PCI should be performed in patients with
STEMI and ischemic symptoms of less than 12 hours’
duration.
I
IIa
IIb
III
Primary PCI should be performed in patients with
STEMI and ischemic symptoms of less than 12 hours’
duration who have contraindications to fibrinolytic
therapy, irrespective of the time delay from FMC.
I
IIa
IIb
III
Primary PCI should be performed in patients with
STEMI and cardiogenic shock or acute severe
HF, irrespective of time delay from MI onset.

14. Primary PCI in STEMI
I
IIa
IIb
III
Primary PCI is reasonable in patients with STEMI if
there is clinical and/or ECG evidence of ongoing
ischemia between 12 and 24 hours after symptom
onset.
I
IIa
IIb
Harm
III
PCI should not be performed in a noninfarct artery at
the time of primary PCI in patients with STEMI who
are hemodynamically stable

15. Primary PCI in STEMI

16. PCI of a Noninfarct Artery Before Hospital Discharge:
Recommendations
CLASS I
1. PCI is indicated in a noninfarct artery at a time
separate from primary PCI in patients who have
spontaneous symptoms of myocardial ischemia. (Level
of Evidence: C)
CLASS IIa
1. PCI is reasonable in a noninfarct artery at a time
separate from primary PCI in patients with
intermediate- or high-risk findings on noninvasive
testing. (Level of Evidence: B)

17. Multivessel coronary artery disease is present in 40% to 65%
of patients presenting with STEMI who undergo primary PCI
and is associated with adverse prognosis.
Studies of staged PCI of noninfarct arteries have been
nonrandomized in design and have varied with regard to the
timing of PCI and duration of follow-up.
These variations have contributed to the disparate findings
reported, although there seems to be a clear trend toward
lower rates of adverse outcomes when primary PCI is limited
to the infarct artery and PCI of a noninfarct artery is
undertaken in staged fashion at a later time.

18. The largest of these observational studies compared 538 patients
undergoing staged multivessel PCI within 60 days of primary PCI
with propensity-matched individuals who had culprit-vessel PCI
alone.
Multivessel PCI was associated with lower mortality rate at 1 year
(1.3% versus 3.3%; p0.04). A none significant trend toward a lower
mortality rate at 1 year was observed in the subset of 258 patients
who underwent staged PCI during the initial hospitalization for
STEMI.

19. Although fractional flow reserve is evaluated infrequently in
patients with STEMI, at least 1 study suggests that
determination of fractional flow reserve may be useful to
assess the hemodynamic significance of potential target
lesions in noninfarct arteries.
The writing committee encourages research into the benefit
of PCI of noninfarct arteries in patients with multivessel
disease after successful primary PCI

20. Prognostic Impact of Staged vs. “Onetime”
Multivessel PCI in AMI
Retrospective analysis of 668 pts from HORIZONS-AMI
• One-time multivessel PCI was associated with higher rates of
all-cause and cardiac mortality as well as stent thrombosis
compared with staged PCI
• The mortality advantage was maintained in a subgroup of pts
undergoing „truly elective‟ multivessel PCI
• In multivariable analysis, staged vs. onetime PCI was an
independent predictor of 1-year mortality
Implications: Deferred angioplasty of significant nonculprit lesions
should be the default strategy for patients undergoing primary PCI.
Kornowski R, et al. J Am Coll Cardiol.
2011;58:704-711.

21. Culprit Vessel Only vs. Multivessel and
Staged PCI for Multivessel Disease in
STEMI Patients
Meta-analysis of 4 prospective and 14 retrospective studies (n = 40,280)
Staged PCI was associated with lower short- and long-term
mortality compared with culprit-vessel-only and multivessel PCI
Multivessel PCI was linked to the highest mortality rates at both
short- and long-term follow-up
The best strategy in pts with cardiogenic shock remains
uncertain
Implications: In STEMI pts, significant nonculprit lesions should be
treated only during staged procedures, a finding that supports
guidelines.
Vlaar PJ, et al. J Am Coll Cardiol.
2011;58:692-703.

22. Multivessel Coronary Artery Revascularization vs.
Culprit-Only Revascularization in STEMI Patients
Meta-analysis of 19 studies (n = 61,764), including 2 randomized trials.
• Within 30 days, there was no difference between groups for
mortality, MI, stroke, and TVR, but multivessel PCI decreased
repeat PCI by 44% and MACE by 32%
• Over mean follow-up of 2 years, there was no difference
between groups for MI, TVR, or stent thrombosis, but
multivessel PCI lowered mortality by 33%, repeat PCI by 43%,
and MACE by 40%
Implications: A large-scale randomized trial is needed to evaluate
comparative efficacy between multivessel revascularization and a
culprit-only strategy.
Bangalore S, et al. Am J Cardiol.
2011;Epub ahead of print.

23. 55 YO male, initial presentation of CAD
Anterior STEMI – 6 hours of chest pain

ECG: Ant. ST Elevation with RBBB
 100/70, pulse 95, O2Sat =96%
BP
.T
otal LAD
• Culprit
• >90% Prox. CX
• Dominant
• 50% Left Main
Small (non dominant)
RCA

24. 55YO male, initial presentation of CAD
Anterior STEMI – 6 hours of chest pain

ECG: Ant. ST Elevation with RBBB
 100/70, pulse 95, O2Sat =96%
BP
What to do?
1. Culprit only (LAD)
2. LAD and CX
3. LAD now and
CX later
(Staging)
• When?
4. Other
Small (non dominant)
RCA

25. Why to perform non-culprit
PCI
• Improve hemodynamics
– Hypercontraction of non-infarct territory (especially
important in patients with cardiogenic shock)
• Prevent reinfarction
– Vulnerable non-culprit lesion can become culprit
(“pan-coronary inflammation”)
• Patient is already receiving aggressive
antithrombotic therapy
– Protected from complications?
• Decrease the need for repeat procedures
– Associated morbidity and cost

26. Why not to perform nonculprit PCI (1)

Ischemic complications may lead to
severe hemodynamic compromise

There is already myocardial dysfunction
secondary to the damage from the
culprit

There is a risk of ischemic complication
in every PCI

Risk is higher in the setting of MI due to
the generalized inflammatory condition

Risk of transformation to culprit during
hospitalization is extremely low

Patient receiving aggressive adjunct
therapy

27. Why not to perform nonculprit PCI (2)

Contrast nephropathy

Increased contrast load in the setting of
unknown kidney function in a patient
with decreased renal blood flow (due to
the infarction)

Non culprit lesion may not be associated
with future symptoms/ ischemia

Overestimation of severity at time of
acute angiography?

28. US National Cardiovascular Data Registry - STEMI
Single vs. Multivessel Procedures during Primary PCI
Hospital Mortality
Unadjusted Data
% death
P= 0.01
Guidelines not
necessarily supported by
literature
P< 0.01
Cavender et al. Am J Cardiol
2009

29.  Four prospective and 14
retrospective studies
involving 40,280 patients
were included
 Pairwise comparison
among 3 post culprit PCI
strategies:
1. Culprit only
2. Staged revascularization
3. Complete revascularization
J Am Coll Cardiol 2011;58:692–703

30. Short Term Mortality – Pairwise Meta-Analysis
Prospective RCT
Registry
Prospective and retrospective data
lead to different results
Suggestive of significant selection bias
Combined
Culprit
Multivessel

31. Conclusions
 Retrospective studies are strongly limited by
selection bias and prospective randomized
studies are small and inconclusive
 Staged revascularization emerges as the
preferred approach for stable patients
 Non-culprit revascularization strategy should
be individualized based on patient‟s
characteristics

32. Back to the Patient
“individualized” decision for this patient:

Stent the non-culprit first to enable
safer treatment of the LAD lesion

Limited reserve due to the
specific
anatomy

33. Final Result

34. Thanks