September 13th, 2013
Should We Treat Nonculprit Lesions During PCI for STEMI?
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.