September 13th, 2013

Should We Treat Nonculprit Lesions During PCI for STEMI?

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CardioExchange’s Rick Lange and David Hillis interview David Wald about his group’s recently published findings from the PRAMI trial of “preventive” PCI in STEMI patients.

Based on results of previous nonrandomized, observational studies, stenting non-infarct coronary stenoses during primary PCI has been discouraged. The Preventive Angioplasty in Acute Myocardial Infarction (PRAMI) trial in 465 STEMI patients assessed whether performing PCI of non-infarct arteries (termed “preventive PCI”) during primary PCI (i.e., “therapeutic PCI”) would reduce the combined incidence of cardiac death, nonfatal MI, or refractory angina compared with PCI of the infarct artery only.

The PRAMI investigators report that “The use of preventive PCI to treat noninfarct coronary-artery stenoses (>50% luminal narrowing*) immediately after PCI in the infarct artery conferred a substantial advantage over not performing this additional procedure. The combined rate of cardiac death, nonfatal MI, or refractory angina was reduced by 65%, an absolute risk reduction of 14 percentage points over 23 months.”  *italics indicate added phrase

Patients not included in the study were those with (a) left main disease (>50%) or left main equivalent (LAD and circumflex ostial stenoses >50%); (b) nonculprit vessel reference diameter <2.5 mm; (c) previous coronary artery bypass graft surgery; (d) chronic total occlusion as the only noninfarct stenosis; or (e) cardiogenic shock.

PRAMI has the potential to change the recommended revascularization approach in STEMI patients.

Lange and Hillis:  Scrutiny of the data reveals that total deaths did not differ between the groups; 12 patients in the preventive PCI group and 16 in the therapeutic PCI group (with 2 of these before hospital discharge).  Hence, the benefit of preventive PCI appears to be a reduction of subsequent nonfatal MI and refractory angina. Is this correct?

Wald: In trials such as this, all-cause mortality is an insensitive outcome measure. The results relating to the primary outcomes are the relevant measures of efficacy. An assessment of noncardiac mortality is a safety check, and the rates were similar in the two groups — which is reassuring.

Lange and Hillis: Whenever a patient has residual coronary stenoses that are not stented, the potential of treatment bias arises.  The PRAMI trial is identified as being “single blind.”  Who was unaware of the treatment allocated? Did the interventional cardiologist not inform the patient or the treating physician how many vessels were stented?  

Wald: The patients were not aware of their assignment. It was explained to them that knowledge of the assigned treatment may bias the study, and this was accepted. The physicians were aware of the assignment.

Lange and Hillis: When PCI is compared with medical therapy, it reduces spontaneous MI at the risk of procedural MI without any difference in all MI (Bangalore et al, Circulation 2013;127:769). Because only spontaneous MIs were assessed in PRAMI, does this overestimate the benefit of preventive PCI in reducing all MIs?

Wald: It would be difficult to determine procedural MIs in this trial because all patients were having a spontaneous STEMI. The overall results would suggest that any adverse effect of procedural MI is small.

Lange and Hillis: Although the incidence of chest pain was similar in the preventive and therapeutic PCI groups (13% vs 16%, respectively), the incidence of “refractory angina” — one of the primary endpoints — was different (5% vs 13%, respectively; P=0.002).  Please explain.

Wald: The former comparison (13% v 16%) relates to the extent to which ischaemia testing was used to investigate chest pain in the Preventive and No Preventive PCI groups after randomization. The latter comparison (5% v 13%) relates to refractory angina as defined in the paper.

Lange and Hillis: In the therapeutic PCI group, testing for ischemia was done more frequently in asymptomatic than in symptomatic subjects, whereas in the preventive PCI group it was done primarily in symptomatic patients. You conclude that “…these findings suggest that preventive PCI may lead to less ischemia testing and that when such testing is performed, it tends to be in patients with symptoms.” An alternative explanation is that the physicians had a bias toward revascularization, which led to more testing — and perhaps revascularization — in asymptomatic patients who did not undergo preventive PCI. How would you respond?

Wald: This is possible. To the extent that there may have been a bias towards more revascularization in the No preventive PCI group, this is likely to dilute the effect of Preventive PCI.

Lange and Hillis: Much attention has recently been focused on preventing unnecessary PCIs (i.e., in patients without symptoms or hemodynamically significant stenoses), in part related to the vagaries of visually estimating stenosis of “intermediate” severity. PRAMI has the potential of substantially increasing the use of stents in STEMI patients. How did you ensure that the PCI was not applied to <50% stenoses? Should fractional flow reserve (FFR) be measured to ensure that only hemodynamically significant lesions are stented?

Wald: Participating physicians accepted the >50% stenosis cut-off for stenting, and to the best of our knowledge, this was applied. Whether FFR in STEMI patients would be better is unknown.

One Response to “Should We Treat Nonculprit Lesions During PCI for STEMI?”

  1. Fahim H Jafary, MD, FACC, FSCAI says:

    Thanks for the write up above. I found the PRAMI trial definitely thought provoking yet difficult to interpret for several reasons

    – first is the obvious “logic” which says that an additional stent in a non-culprit vessel should increase the risk of stent thrombosis in the thrombotic post MI milieu but this trial is suggesting something quite the opposite.

    – prior studies have never shown “preventive” PCI to benefit – that said, those data are in stable patients and the PRAMI patients were “hot” (ie, have inflamed arteries including non-culprit)

    – the cut off for stenosis in the non-culprit vessel was > 50% which we all know means that many of them would have been potentially non-significant (for example a 60% lesion which we all know is more often not flow limiting). This makes the results even more difficult to make sense of because a benefit was seen. On the other hand, is it possible that the enrolling physicians took patients with VERY SEVERE (like > 95%) lesions in the non-culprit vessels ? In that case one could imagine a potential benefit vs. medical therapy

    – there was a > 60% reduction in events including non-fatal MI (significant) as well as cardiac death (trend) – almost seems too good to be true

    – the recurrent events that occurred in the non-PCI arm …. we are not told whether they occurred in the unfixed non-culprit vessels or somewhere else
    – the non-culprit vessels were stented in the same setting (they actively discouraged a staged PCI later unless there was a clinical indication). I assume they did so to make the trial as “clean” as possible but does this mean that you have to stent the non-culprit immediately in order to accrue benefits ?

    – all patients got aspirin plus either clopidogrel, ticagrelor or prasugrel (based on “physician’s discretion”). As far as I can tell, I didn’t see any reporting of whether there were any imbalances in the use of the newer more potent agents but if the stent arm somehow got more of prasugrel or ticagrelor, that could have swayed the results in favor of stenting the non-culprit

    – Interestingly, the Kaplan Meier curves appear to separate out VERY early (around a month I think) so this is not a long term issue, it seems like it’s a relatively early benefit

    – also interestingly, all this occurred despite aggressive and good medical therapy in both arms

    My take on this:
    – stent the culprit during the MI as usual
    – I usually do the non-culprit vessel around a month down the line – I may rethink my strategy and consider doing it during the same admission. I’d still be uncomfortable stenting the non-culprit right there and then if, for nothing else, contrast load and stability reasons.
    – we need to wait for the COMPARE-ACUTE trial which is testing almost exactly the same strategy but the non-culprit vessel PCI is FFR guided (FFR non-culprit vessel immediately after stenting the culprit –> PCI same session or a day or two later if indicated)