PRAMI Trial

Abdelkader Almanfi, MD, MRCP-UK

Texas Heart Institute

Journal club

11/04/2013

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)

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 MedVolume 369(12):1115-1123

September 19, 2013

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.

Enrollment and Follow-up.

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

Kaplan–Meier Curves for the Primary Outcome.

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

Characteristics of the Patients at Baseline.

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

Details Regarding PCI and Medical Therapy at Discharge.

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

Prespecified Clinical Outcomes.

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

Conclusions

• In patients with STEMI and multi-vessel coronary artery disease undergoing infarct-artery 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.

Critics about the study:

- Sample size is small

-Larger number of patients were inferior infarcts

- EF was not reported in the study

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

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.

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.

I IIa IIb III

Primary PCI in STEMI

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 III

PCI should not be performed in a noninfarct artery at the time of primary PCI in patients with STEMI who are hemodynamically stable

I IIa IIb III

Harm

Primary PCI in STEMI

PCI of a Noninfarct Artery Before Hospital Discharge: Recommendations

CLASS I1. 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 IIa1. 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)

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.

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.

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

Kornowski R, et al. J Am Coll Cardiol.2011;58:704-711.

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.

Vlaar PJ, et al. J Am Coll Cardiol.2011;58:692-703.

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 PCIMultivessel 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.

• 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%

Meta-analysis of 19 studies (n = 61,764), including 2 randomized trials.

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.

Multivessel Coronary Artery Revascularization vs. Culprit-Only Revascularization in STEMI Patients

55 YO male, initial presentation of CADAnterior STEMI – 6 hours of chest painECG: Ant. ST Elevation with RBBBBP 100/70, pulse 95, O2Sat =96%

. Total LAD• Culprit

• >90% Prox. CX• Dominant

• 50% Left Main

Small (non dominant) RCA

55YO male, initial presentation of CADAnterior STEMI – 6 hours of chest painECG: Ant. ST Elevation with RBBBBP 100/70, pulse 95, O2Sat =96%

What to do?1.Culprit only (LAD)2.LAD and CX3.LAD now and

CX later

(Staging)• When?

4.OtherSmall (non dominant) RCA

• 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

Why to perform non-culprit PCI

Why not to perform non- culprit PCI (1)

Ischemic complications may lead to severe hemodynamic compromiseThere is already myocardial dysfunction

secondary to the damage from the culprit

There is a risk of ischemic complication in every PCIRisk is higher in the setting of MI due to

the generalized inflammatory conditionRisk of transformation to culprit during

hospitalization is extremely lowPatient receiving aggressive adjunct

therapy

Why not to perform non- culprit PCI (2)

Contrast nephropathyIncreased 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/ ischemiaOverestimation of severity at time of

acute angiography?

US National Cardiovascular Data Registry - STEMI Single vs. Multivessel Procedures during Primary PCI

% d

eath

Hospital Mortality

Unadjusted DataP= 0.01

Guidelines not necessarily supported by literature

P< 0.01

Cavender et al. Am J Cardiol 2009

Four prospective and 14 retrospective studies involving 40,280 patients were included

Pairwise comparison among 3 post culprit PCI strategies:1. Culprit only2. Staged revascularization3. Complete

revascularizationJ Am Coll Cardiol 2011;58:692–703

Short Term Mortality – Pairwise Meta-Analysis

Prospective - RCT

Registry

Combined

Culprit Multivessel

Prospective and retrospective data lead to different resultsSuggestive of significant selection bias

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

Back to the Patient

“individualized” decision for this patient:Stent the non-culprit first to enablesafer treatment of the LAD lesion

Limited reserve due to the specificanatomy

Final Result

Thanks