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Discussion
The main results of this study could be summarized as follows: a) Half of elderly patients (> 75 years old) with STEMI undergoing pPCI present with MVD; b) Nearly half of them underwent multivessel revascularization, with a similar rate of acute or staged procedures and under factors clearly influencing those decisions; c) Multivessel PCI is related with better 2 years outcomes and the benefit was greater if done in staged procedures; d) No harm was found for multivessel PCI during acute procedures; e) Among those patients undergoing multivessel PCI, the achievement of anatomically defined complete revascularization did not have influence on 2 years outcomes.
Routine revascularization of non-culprit lesions before hospital discharge has been supported by the recently published 2017 ESC guidelines in which a class IIa recommendation is given for this strategy . The recommendation for this strategy was class IIb in the 2015 ACC/AHA guidelines . These recommendations are based on the evidence from randomized trials.
The first trial included only 214 patients and after a mean follow-up of 2.5 years, patients allocated to culprit lesion angioplasty-only had more major adverse cardiac events . After this study, four larger randomized clinical trials have been published. Multivessel PCI was done either during the index procedure , staged during hospital admission , or any time before discharge (immediate or staged) . Indication of non-culprit PCI was angiography-guided in lesions with ≥ 50% stenosis , > 70% stenosis , or fractional flow reserve-guided . Primary outcome (composite of different endpoints) was significantly reduced in the multivessel revascularization group in all four trials but mortality was not statistically different in any of these four trials. The pooled analysis of these trials shows that multivessel PCI at index or staged procedures is associated to reduction in MACE due to reduction in urgent revascularization. being the risk of all-cause mortality and spontaneous reinfarction not different. As the optimal timing of revascularization (immediate vs. staged) has not been adequately investigated, no recommendation in favor of immediate vs. staged multivessel PCI can be formulated.
In the particular case of patients with MVD and cardiogenic shock a IIa recommendation has been given for multivessel PCI during index procedure in the 2017 ESC guidelines based on a level C evidence . A meta-analysis of nonrandomized studies suggests that there may be no significant benefit with single-stage multivessel-PCI compared with culprit only-PCI. Furthermore, this recommendation has been definitely challenged by the recently published CULPRIT SHOCK trial. In this trial immediate multivessel PCI increased the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy and the relative risk of death.
In clinical practice there are several factors to consider for performing multivessel PCI at the time of primary PCI including patient stability, ability to accurately assess lesion significance in the setting of acute coronary syndromes, likelihood of procedural success, risk of the intervention, and the potential benefit of revascularization. Furthermore, the presence of unstable morphology in angiography or intracoronary imaging, the use of pressure wire in lesions with stenosis 50–75% and the location of the lesion (if proximal or in a vessel that subtends a significant area of myocardium) play an important role.
Patients over 75 years present particular characteristics that limit the validity of the application of results derived from general population. Thus, evidence is lacking to support any recommendation specifically aimed to the elderly with STEMI and MVD. Advanced age could induce a more conservative approach. In our registry, the proportion of patients with multivessel disease that were revascularized in hospital was 46% and ageing decreased likelihood of non-culprit intervention independently. Female sex was indentified as well as a variable promoting a culprit-only lesion revascularization approach, regardless of the age. Patients in worse clinical condition (Killip class III or IV) were less likely to undergo multivessel revascularization. The lack of supporting evidences at that time and prior negative experiences made the operators less prone to perform multivesel PCI in this setting. This conservative strategy has been proven to be more adequate just recently. In fact, the survival benefit seen in the subgroup of patients with shock undergoing multivessel PCI in this registry support a careful selective indication for multivessel PCI in this critical scenario.
The timing of non-culprit interventions was associated as well with certain variables. Patients with history of previous infarction, anterior infarction, Killip class III–IV or later presentation underwent more frequently multivessel PCI in the pPCI procedure. On the other side, a more extensive disease (three vessel disease) and the use of radial access and drug-eluting stents favored staged procedures. The apparent discrepancy for the Killip class III-IV in both analysis can be explained by the very high mortality of these patients in the first 24–48 h of presentation, which made very difficult for them to be referred for staged procedures, which accounted for almost half of non-culprit PCI procedures. With respect to the higher use of drug-eluing stents in staged procedures this is explained because staged procedures were related with more complex lesions, 3-vessel disease and with patients with Killip class I or II (higher expectancy of long term survival).
Regarding the prognostic implications of the different therapeutic approaches. In this registry, multivessel PCI was associated with an absolute risk reduction of 5% and was an independent predictor (reduction by 40%) over 2 years in the combined incidence of cardiac death and myocardial infarction. The prognostic advantage of multivessel PCI was observed across all the Killip classes. When comparing multivessel revascularization vs. culprit-only revascularization in STEMI, the value of revascularization as an outcome is to some extent questionable and definitely less relevant. That is why a combined endpoint of cardiac death and infarction could be in our view more adequate and so was selected for this study.
With respect to the timing of intervention, the survival curves showed an early separation and this finding could justify a prompt non-culprit PCI. We found that staged PCI of non-culprit lesions was associated to better outcomes. Moreover, in survival curves it appears that patients having non-culprit PCI during pPCI showed a quite similar outcome than those with culprit lesion PCI alone. Nevertheless, though multivessel PCI in acute procedure was clearly associated to a worse patient profile, it was associated to a trend for better outcomes in multivariant analysis.
Finally, completeness of revascularization emerged as an independent predictor of cardiac death and myocardial infarction in overall population with MVD. However, among those patients who underwent multivessel PCI, the achievement of anatomically defined complete revascularization did not appear to have influence on two years outcomes. These results suggest that not all lesions have the same prognostic impact on outcomes, and perhaps only the treatment of non-culprit lesions located in proximal or large segments of main coronary arteries is prognostically relevant. Furthermore, lesions with 50–75% stenosis left untreated could be functionally nonsignificant. In this regard, a combination of angiographic and functional criteria (based on fractional flow reserve) could be more adequate no define complete revascularization.