PRAMI TRIALDR.PRAVEEN NAGULA

Preventive Angioplasty in Acute Myocardial

Infarction trial

David S Wald et al,NEJM 2013;369:1115-23

Single blind randomized study

background In acute ST segment elevation myocardial infarction(STEMI),the

use of percutaneous coronary intervention(PCI) to treat the artery responsible for the infarct(infarct or culprit artery) improves prognosis.

Whether PCI in noninfarct arteries is significant in

preventing future cardiac events??

THE PREVENTIVE PCI

METHODS From 2008 through 2013 465 patients at five coronary care centers in UK. Consecutive patients of any age with acute STEMI and

multivessel coronary disease detected at the time of emergency PCI.

Trial was limited to patients with STEMI.

Inclusion criteria Patients were considered for eligibility after undergoing PCI

in the infarct artery, in catheterization laboratory.

Deemed to be eligible if the infarct artery had been treated successfully and there was stenosis of ≥50% in one or more coronary arteries other than the infarct artery and treatable by PCI.

The treating cardiologist had to consider that both infarct artery- only PCI and preventive PCI would be acceptable treatment options.

Exclusion criteria

Patients in Cardiogenic shock Unable to provide consent Previous CABG Left main ,ostial LAD,LCX stenosis of ≥ 50%(CABG

indications) Non infarct stenosis being a chronic total occlusion (PCI is C/I).

OutcomesPrimary outcome: Composite of death from cardiac causes,non fatal myocardial

infarction,or refractory angina. Each component was assessed individually.

Secondary outcomes: Death from noncardiac causes Repeat revascularization procedures (PCI or CABG).

Independent cardiologist and cardiac surgeon who were not notified about study group assignments examined specified primary and secondary outcomes.

Statistical analysis For a power of at least 80% to detect a reduction in risk of 30% in

the preventive PCI group,as compared with other,at a level of 5% significance, assuming a 20% annual rate of the primary outcome in the latter group – 600 patients to be enrolled.

Survival outcomes by log rank statistic. Stopping criteria included a clear answer to the trial question from

the emerging literature or from the results of the trial,(P<0.001).

All were included in analysis on an intention to treat basis.

Results Recruitment stopped early after noting a significant between

group difference (P<0.001) in the incidence of the primary outcome favoring the preventive PCI.

465 patients were enrolled.

234 –preventive PCI,231 to non preventive PCI. Mean follow up was 23 months.

67% patients were followed for atleast 1yr. 46% pts -2 yrs. 10 pts in preventive PCI ,8 in the other group lost to follow up.

Preventive PCI no Preventive PCI

Primary outcome 21 pts 53 pts

Event rates 9/100 23/100

Absolute risk reduction

14%

STEMI 2 9

NSTEMI 5 11

Stent thrombosis 2 3

Ischemia testing 1/6 1/3

asymptomatic 8 44

symptomatic 31 37

Risk reduction in the preventive PCI group was evident within the 6 months after the procedure and was maintained thereafter.

The rate of death from non cardiac causes did not differ significantly between the two study groups.(hazard ratio,1.10;95%CI,0.38 to 3.18;P=0.86)

The results were not materially affected by the five prespecified covariates – age sex,± of diabetes,infarct location,and the number of coronary arteries with stenosis.

Procedure time,fluoroscopy dose,and contrast volume were increased in the preventive PCI group.

Rates of complications(procedure related stroke,bleeding requiring transfusion,surgery,CIN requiring dialysis)were similar in both groups.

Median length of stay in the hospital was 2 days with 95% patients being discharged within 1 week.

Primary outcomes

DiscussionIn one study 69 patients were randomly assigned (3:1ratio) to preventive

PCI in patients with acute STEMI undergoing PCI in the infarct artery.

At 1 year, in the preventive PCI group,there were nonsignificant reductions in the rates of repeat revascularization (17% and 35%)and cardiac death or myocardial infarction (4%and 6%) respectively.

Di Mario et al ,HELP AMI study.Int J Cardiovasc Intervent 2004;6:128-33

In the other trial, 214 patients were randomly assigned to one of three groups; No preventive PCI(84 pts),immediate preventive

PCI(65pts),and staged preventive PCI performed during a second procedure about 40 days later(65 pts)

At 2.5 yrs the rate of repeat revascularization was less frequent in the immediate and staged preventive PCI groups combined,as compared with the group receiving no preventive PCI(11% and 33% respectively).

Nonsignificant decrease in the rate of cardiac death (5 and 12 % respectively).

Politi et al , Heart 2010;96:662-7.

Studies MVA IRA MORTALITY/events

P value Others

Kong et al 632 1350 0.8vs2.3% P-0.018 OR-0.27

Khattab et al 28 45 24 vs28% P-0.73

Qarawani et al 95 25 16.7vs52%Renal dysf(8.4% vs 4%)

P-0.0001

Chen et al 239 1145 equal P-0.78

Varani et al 243 156 2.3%vs 6.3% P-.023

Preventive PCI beneficial

Politi L et al, HEART 2010;96:662-7. Kong JA et al ,Coronary Artery Dis 2006;17:71-5.

Khattab A et al , Clin Rese Cardiol 2008;97:32-8. Qarawani D et al ,Int J Cardiol 2008;123:288-92.

Chen LY et al ,Am J Cardiol 2005;95:349-54. Varani et al ,Catheter Cardiovasc Interven 2008;72:927-33.

Risks outweigh benefits

Corpus et al, Am Heart J 2004;148:493-500 Roe et al, Am J Cardiol 2001;88:170-3,A6.

Cavender MA et al, Am J Caridol 2009;104:507-13. Hannan EL et al, JACC Cardiovasc Interven 2010;3:22-31

Toma et al ,APEX-AMI trial, Eur Heart J 2010;31;1701-7.

Study IRA MultiPCI Pvalue

Roberto et al reinfarction 2.8% 13.8% 0.001

revascularization 25% 15% 0.007

Cavender et al Mortality in pts with Card.shock

27.8% 36.5% 0.01

overall 7.9% 5.1% 0.01

Why the previous studies deferred???

Lack of statistical powerReliance on repeat revascularization

What do guidelines say ??Current guidelines recommend only infarct artery only PCI in patients with multivessel disease,owing to a lack of evidence

with respect to preventive PCI

Questions unaswered?1.Immedicate versus staged PCI.2.Are the benefits of preventive PCI applicable to NSTEMI.3.Do the benefits extend to the stenoses less than 50%.4.Level of stenoses at which the risks of PCI outweigh benefits.5.Would FFR offer an advantage over angiographic visual assessment in guiding preventive PCI

conclusions In patients undergoing emergency infarct artery PCI for

acute STEMI, preventive PCI of stenoses in noninfarct arteries reduced the risk of subsequent adverse cardiovascular events,as compared with PCI limited to the infarct artery.