Background
Primary percutaneous coronary intervention (P-PCI) of the culprit artery is widely used in patients with ST-segment elevation myocardial infarction (STEMI). Approximately 50 % of STEMI patients have multivessel disease (MVD) [
1,
2]. Non-culprit lesions are not just “bystanders”, as a pathophysiological inflammation process in acute myocardial infarction could cause plaque instability [
3,
4]. Previous research has also shown that STEMI patients with MVD have higher mortality rates and a greater incidence of non-fatal reinfarction than those without MVD [
1,
2]. However, the optimal management of STEMI patients with MVD remains undetermined [
5‐
7]. Although a number of randomized controlled trials (RCTs) [
8‐
11], including the PRAMI [
9], CVLPRIT [
10] and DANAMI-3—PRIMULTI [
11] trials, have indicated the clear benefits of complete PCI, other RCTs [
12‐
14], including the PRAGUE-13 trial [
12], found no difference between complete and culprit-only revascularization in STEMI patients with MVD. Furthermore, observational studies [
15‐
21] and meta-analyses [
22‐
24] also demonstrated conflicting results.
The present study aimed to determine the benefits and safety of staged complete revascularization in STEMI patients with MVD undergoing P-PCI.
Discussion
The present study determined the effects of different treatment strategies on STEMI patients with MVD in a real-world clinical setting. The main findings were as follows: (1) staged complete revascularization significantly reduced not only the rate of the composite of cardiac mortality or nonfatal reinfarction, but also the need for unplanned repeat revascularization; (2) no significant differences in all-cause mortality, cardiac mortality or nonfatal reinfarction were observed between the treatment strategies; (3) staged complete revascularization did not significantly increase periprocedure-related complications.
Toyota et al. analyzed 1311 STEMI patients with MVD undergoing P-PCI from the CREDO-Kyoto AMI Registry in Japan (681 in the staged PCI group versus 630 in the culprit-only PCI group), and reported that staged PCI was associated with a lower 5-year composite of cardiac mortality and myocardial infarction compared with culprit-only PCI [HR: 0.67, 95 % CI: 0.44–0.99,
P = 0.045] [
19]. Our findings also showed a lower composite of cardiac mortality and nonfatal reinfarction in the SR group. A similar conclusion was found in the CvLPRIT and DANAMI-3—PRIMULTI trials [
10,
11]. However, no studies have found significant differences in cardiac mortality [
8‐
12,
19] between the treatment groups. Furthermore, most studies [
8‐
12,
17,
19,
20] found no significant differences in nonfatal reinfarction, except for the PRAMI trial [
9] and a recent meta-analysis [
23]. Our study also failed to find significant differences in cardiac mortality and nonfatal reinfarction between the two groups. It was demonstrated that staged complete revascularization significantly reduced the need for unplanned repeat revascularization; however, the Japanese study [
19] and CvLPRIT trial [
10] found no significant differences, and the proportion of patients with three-vessel disease may have played an important role. There was a higher proportion of three-vessel disease in the CR group in our study than in the other two previous studies. In other words, the higher the proportion of three-vessel disease, the higher the proportion of ischemia-driven unplanned repeat revascularizations. Meta-analyses have also confirmed that multivessel PCI will reduce the need for repeat revascularization [
22‐
24]. Different to other studies [
17‐
19], our study found no significant differences in all-cause mortality. It is possible that the follow-up duration in our study was too short to detect significant differences in all-cause mortality: 3-year follow-up in our study, compared with 5-year and 7-year follow-up in the other two studies [
18,
19]. In addition, the sample size in our study was relatively small, 602 individuals compared with 8822 and 1311 in the other two studies [
18,
19]. Accordingly, adequately powered randomized studies should be performed to obtain meaningful conclusions, such as in the COMPLETE trial (ClinicalTrials.gov NCT01740479).
The safety concerns regarding complete revascularization include the risk of procedural complications, longer procedural time, contrast nephropathy, and stent thrombosis which may increase in a prothrombotic and proinflammatory state in the presence of STEMI. Despite this, our study showed no increase in major bleeding, contrast-induced nephropathy, stroke, acute or subacute stent thrombosis. This was consistent with previous studies [
8,
10‐
12,
19].
There are still several problems related to the treatment of STEMI. First, is staged complete revascularization better than "one-time" complete revascularization? While analysis from the HORIZONS-AMI trial preferred staged complete revascularization [
15], other studies found "one-time" complete revascularization safe and effective [
20,
21]. Second, what is the appropriate timing of staged revascularization? Different studies had different time cut-off points; however, no study could confirm a favored time cut-off point. Third, should fractional flow reserve (FFR) or a non-invasive physiological stress test be used to determine indications for staged revascularization in addition to angiography? FFR measurements of non-culprit lesions could be performed immediately [
28] or several days or weeks [
7] after treatment of the culprit vessel. To date, studies with FFR as the reference [
11,
13,
14] did not have clearer conclusions than those without FFR as the reference [
8‐
10]. The COMPARE ACUTE trial (ClinicalTrials.gov NCT01399736), an ongoing prospective randomized study comparing a FFR-guided multivessel PCI undertaken during primary PCI of the culprit vessel only, may help us to define the role of FFR in STEMI patients with MVD. Fourth, do the benefits extend to non-culprit stenoses of less than 70 % or 50 %? The level of non-culprit stenosis at which the risks of PCI surpass the benefits is still uncertain. In addition to FFR, intracoronary imaging such as an intravascular ultrasound study (IVUS) and optical coherence tomography (OCT) could be useful tools for non-culprit lesion revascularization. IVUS and OCT could help us describe
in vivo the pathological morphology of plaque associated with an impaired myocardial blush and slow flow leading to a worse prognosis [
29]. As for the use of IVUS and OCT, a per-patient tailored therapy may be achieved.
Limitations
This study had several limitations. First, the study was retrospective and observational, thus potential confounders and selection bias could not be completely adjusted. Second, this was a single center study. Third, the significance of non-culprit lesions was assessed only on angiography, and ischemia tests such as FFR were absent. Fourth, the long symptom to balloon time in this study may have had an impact on the study results, as analysis of the HORIZONS-AMI trial results suggested that a delay in mechanical reperfusion therapy during STEMI is associated with greater injury to the microcirculation [
30], and another study showed that a symptom-onset-to-balloon time >4 h was an independent predictor of one-year mortality [
31]. Finally, the incidence of the primary composite end-point was quite low during the follow-up period. The low number of events may be a limitation in the overall interpretation of the study results.
Acknowledgements
No one who contributed towards the article who does not meet the criteria for authorship.