The Randomized Trial of Preventive Angioplasty in Myocardial Infarction (PRAMI) [29], enrolled 465 patients with acute STEMI who were undergoing infarct‐artery PCI and randomly assigned them to either preventive PCI (immediate PCI of non‐IRA lesions), or no preventive PCI (culprit lesion only strategy without any further treatment strategy for non‐IRA lesions). Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia. The trial was stopped early in January 2013, after the data and safety monitoring committee felt the results to be conclusive, revealing, after a mean follow‐up of 23 months, a HR for the primary outcome of death from cardiac causes, nonfatal myocardial infarction, or refractory angina of 0.35 (95% CI 0.21 to 0.58; p<0.001) for the preventive PCI group.
Similarly, the Complete Versus Lesion‐Only Primary PCI trial (CvLPRIT) [30], was a multicenter, open‐label trial which randomized 296 patients in seven UK centers to either in‐hospital complete revascularization, either at the time of primary PCI or before discharge, or IRA‐only revascularization. Within a period of 12 months post intervention, the primary endpoint of all‐cause death, recurrent MI, heart failure and ischemia driven revascularization occurred in 10.0% of complete revascularization group versus 21.2% of the IRA‐only revascularization group (HR 0.45; 95% CI 0.24–0.84, p = 0.009). In particular, the primary endpoint results were not driven by differences in revascularization rates alone. Indeed, more recent long‐term follow up data [31], with a median follow up time of 5.6 years, revealed that these benefits are sustained in the long term.
The DANAMI‐3‐PRIMULTI study [32], showed performing FFR‐guided complete revascularization during the index hospitalization for STEMI patients initially treated with primary PCI led to a reduction in a primary composite endpoint of all‐cause mortality, non‐fatal reinfarction and ischemia‐driven revascularization of lesions in non‐infarct related arteries over a median follow‐up of 27 months (HR 0.56, 95% CI 0.38–0.83; p = 0.004). This was driven by a significant difference in reinterventions, rather than mortality or reinfarction rates. The COMPARE‐ACUTE study showed similar results mainly on repeat revascularizations [33].
However, the most recent randomized controlled trial in this area, the COMPLETE trial [34], which randomized more than 4000 patients at 140 centers to complete revascularization or culprit lesion‐only PCI, favored full revascularization, at least in terms of non‐fatal myocardial reinfarction, rather than all‐cause death or cardiovascular death. In this trial, PCI of non‐culprit lesions was performed as a staged procedure, either during the index admission or following discharge, up to 45 days after randomization. PCI of the non‐culprit lesions was performed regardless of symptoms, but only if, on angiography, the patient had a stenosis of >70%, or between 50–69% with a fractional flow reserve (FFR) value of <0.8. Of note, those that had FFR performed comprised less than 1% of the study population. The first coprimary endpoint was a composite of death from cardiovascular causes or new myocardial infarction. At a median follow‐up of three years, the first coprimary outcome had occurred in 7.8% of patients in the complete‐revascularization as compared with 10.5% of patients in the culprit‐lesion‐only PCI group (hazard ratio 0.74; 95% CI 0.6 to 0.91; p<0.004).
In terms of timing of the non‐IRA artery intervention, a recent meta‐analysis of RCTs suggested that there is an additional benefit to performing the multivessel PCI at the time of the index procedure (HR 0.45, 95% CI 0.24–0.84 versus HR 0.75, 95% CI 0.55–1.02, p value for between group difference <0.001) [35]. However, factors influencing the operator’s choice of an immediate versus staged intervention, in particular operator experience, lesion complexity and stenosis severity, renal function, out‐of‐hours timing serve to confound this result, and ultimately the data for the approach taken in the COMPLETE trial, of staged multivessel PCI, is in our opinion, more robust.
ESC guidelines recommend consideration of routine revascularization of non‐IRA lesions in STEMI patients with multivessel disease prior to hospital discharge (Class IIa) [3]. The 2015 ACC/AHA/SCAI focused update on primary PCI – published before most of the relevant evidence has been published – is somewhat more conservative, with a class IIb recommendation that PCI of a non‐IRA may be considered in hemodynamically stable STEMI patients, either at the time of primary PCI or as a planned staged procedure [18].
Primary PCI in the setting of cardiogenic shock
The early seminal study in the setting of cardiogenic shock was the Early Revascularisation in Acute Myocardial Infarction Complicated by Cardiogenic Shock (SHOCK) trial [36], published in 1999. This trial demonstrated that emergency revascularization (either PCI or coronary artery bypass grafting [CABG]) resulted in a significant reduction in mortality in the revascularization group (50.3% vs 63.1%; p = 0.027) at six months. Of note, the 30‐day follow‐up did not show a significant mortality difference. On further follow up, this mortality difference at six months was sustained at 12 months (53.3% vs 66.4%; p = 0.03),37 and 6 years (67.2% vs 80.4%; p = 0.03) [38].
There are no randomized controlled trials assessing the efficacy of PCI vs CABG in cardiogenic shock.
In 70–80% of cases of patients with ischemic cardiogenic shock, multivessel coronary disease is found on initial diagnostic angiogram [39]. The CULPRIT‐SHOCK study was designed to investigate whether PCI of the culprit‐lesion‐only, with the option of staged revascularization of the non‐culprit lesions, would result in better clinical outcomes than immediate multivessel PCI in the case of patients who present with multivessel coronary artery disease, acute MI and cardiogenic shock [40]. In summary, this was an investigator‐initiated, 1:1 randomized, open‐label multicenter trial including patients with acute STEMI or NSTEMI complicated by cardiogenic shock, with planned early revascularization by means of PCI and an identifiable culprit lesion. A total of 706 patients were randomized to the culprit‐lesion‐only PCI group (351 patients) or the multivessel PCI group (355 patients). At 30 days, the rate of the composite primary endpoint of death or renal‐replacement therapy (RRT) was significantly lower in the culprit‐lesion‐only PCI group than in the multivessel PCI group (45.9% vs 55.4%; relative risk, 0.83; 95% CI 0.71 to 0.96, p = 0.01). This was driven principally by increased rates of death in the multivessel PCI group, rather than an increased need for RRT. This finding led to a change in the recommendations in the updated ESC Revascularization guidelines with a down‐grading of immediate multivessel PCI to a class III B recommendation [22].
Pharmacological management
Antiplatelet therapy
According to ESC/AHA guidelines, patients undergoing primary PCI should receive DAPT (i.e. a combination of aspirin and a P2Y12 inhibitor), and a parenteral anticoagulant during PCI [3,4].
The 3rd generation thienopyridine prasugrel and the reversible P2Y12 inhibitor ticagrelor have largely replaced the 2nd generation thienopyridine clopidogrel apart from in a select few situations (age >75 years, weight <60 kg, prior stroke or TIA, in the setting of oral anticoagulant use, excessive risk of bleeding), given its relatively slow onset of action and large variability in inter‐patient response. Where clopidogrel is used, it is recommended that a 600 mg loading dose be used, given the evidence of faster onset of action and less inter‐patient variability at this dose [41].
Prasugrel
Prasugrel, like clopidogrel, is a prodrug, however, it has a significantly shorter metabolic pathway, allowing for a faster and more complete inhibition of platelet aggregration [42]. The seminal TRITON‐TIMI study [43], included 3534 patients with STEMI, and showed a significant benefit of prasugrel compared to clopidogrel overall, and particularly in the STEMI cohort (hazard ratio for primary efficacy end point of death from cardiovascular causes, nonfatal MI, or non‐fatal stroke 0.79; 95% CI 0.65–0.97; p = 0.02). The Elderly ACS 2 Trial assessed the efficacy and safety of prasugrel vs clopidogrel in the >74 year old ACS population in general, but STEMI patients made up 42% of cases [44]. Overall, and in particular in the STEMI cohort, there was no difference detected in a primary endpoint of all‐cause mortality, MI,