Author + information
- Robert J. Applegate, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Robert J. Applegate, Wake Forest School of Medicine, Section of Cardiovascular Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045.
The optimal management of patients with multivessel disease (MVD) and ST-segment elevation myocardial infarction (STEMI) is in flux. The traditional conservative approach to primary percutaneous coronary intervention (PPCI) of the culprit vessel only during STEMI, with the exception of patients who are in shock or are unstable, is being challenged by new randomized clinical trial data suggesting that earlier and more complete revascularization may be more beneficial than culprit percutaneous coronary intervention (PCI) only. A substantial body of published research supports the notion that patients with MVD have worse outcomes than patients with single-vessel disease and that discovery of MVD at the time of PPCI for STEMI is not uncommon. Coupled with a recent emphasis on achieving complete revascularization for patients with MVD, however achieved, it is not surprising that the traditional culprit vessel–only approach to PPCI in STEMI in patients with MVD is coming under closer scrutiny.
A number of single-center experiences and registries have been published, yielding diverse results concerning the merit of earlier revascularization of the nonculprit vessel in a patient presenting with STEMI. Few randomized clinical trial data have existed examining the strategy of earlier and more complete revascularization in patients with MVD and STEMI, until in the past couple of years 4 modestly powered randomized clinical trials have examined this subject. The PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial randomized 465 patients to either culprit-only PPCI or PCI of non-infarct-related lesions with stenoses >50% during the initial procedure (1). The investigators observed a decrease in the composite endpoint out to 23-month average follow-up (9% vs. 23%; p = 0.01). The CvLPRIT (Complete Versus Culprit-Lesion Only Primary PCI) trial randomized 296 patients to infarct-only PPCI versus PCI of MVD either during the initial procedure or as a staged procedure (2). Those investigators also found a reduction in a composite endpoint at 12 months with multivessel PCI versus infarct-only PCI (10% vs. 21%; p = 0.009). The DANAMI-3 PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction) trial randomized 627 patients to culprit vessel–only PPCI versus fractional flow reserve–guided multivessel PCI in a staged fashion (3). In that trial, the multivessel fractional flow reserve–guided approach resulted in a decrease in a composite endpoint compared with infarct-related only (13% vs. 22%; p = 0.004). Last, the PRAGUE-13 (Primary Angioplasty in Patients Transferred From General Community Hospitals to Specialized PTCA Units With or Without Emergency Thrombolysis) trial randomized 214 patients to infarct-only PPCI versus staged multivessel PCI (4). At mean follow-up of 38 months, there was no significant difference in the composite primary endpoint between these 2 strategies (16% vs. 14%; p = 0.41).
These trials have been pivotal in changing the evidence base, and strongly held beliefs, that infarct-only PPCI should be the default strategy for all patients with STEMI, regardless of the presence or absence of MVD. Having said that, however, these studies were at best modestly powered, and they used composite endpoints as their primary outcome measures, driven primarily by the need for repeat revascularization but not mortality. Additionally, these studies varied in the timing of non-infarct-related PCI, divided between PCI for MVD at the index procedure or in a staged manner up to several months later. To address these limitations, in a study reported in this issue of JACC: Cardiovascular Interventions, Tarantini et al. (5) performed a pairwise and network meta-analysis of 3 PPCI strategies for STEMI in patients with MVD: 1) infarct-related artery–only PPCI; 2) multivessel PCI during the index procedure; and 3) staged multivessel PCI.
The investigators identified 13 prospective and 19 retrospective studies encompassing 54,148 patients. As a result, there were 18 comparisons for infarct-only versus single-setting multivessel PCI, 15 comparisons for infarct-only versus staged multivessel PCI, and 9 comparisons for staged multivessel PCI versus culprit-vessel PCI only. Importantly, the primary outcome of this analysis was all-cause mortality. The investigators further stratified the outcomes on the basis of pooled early mortality as well as pooled long-term mortality. In the pooled short-term mortality analysis, staged multivessel PCI was associated with lower mortality compared with infarct-only PCI (1.9% vs. 4.9%; p = 0.02), as well as compared with single-procedure multivessel PCI (1.4% vs. 5.6%; p < 0.001). Infarct-only PPCI was associated with lower mortality compared with single-procedure multivessel PCI (4.9% vs. 6.9%; p = 0.004). In the pooled long-term mortality analysis, similar results were observed, with lower mortality in the multivessel staged PCI strategy versus infarct-only PCI (4.1% vs. 6.8%; p = 0.001) and compared with single-procedure multivessel PCI (3.1% vs. 8.5%; p < 0.0001). As was observed in the pooled early mortality evaluation, infarct-only PPCI was associated with lower mortality compared with single-procedure multivessel PCI (6.9% vs. 8.0%; p = 0.04). The benefit of staged multivessel PCI persisted after excluding patients with cardiogenic shock compared with both infarct-only and single-procedure multivessel PCI, but the differences between infarct-only and single-procedure multivessel PCI were no longer present.
The study by Tarantini et al. (5) is a sophisticated analysis of a complex clinical conundrum. The strength of the study is the large number of patients included and the use of mortality rather than a composite endpoint as the outcome measure of interest. Nonetheless, and as acknowledged by the investigators, there are limitations of this analysis, which should be recognized in using the observations to guide clinical practice. First, the majority of the studies were retrospective, and the decision to perform any of the 3 strategies was driven by local and operator practice, with potentially substantial bias in the types of patients included in each group. For example, the worse outcomes with single-procedure multivessel PCI may represent the belief that the patient was in incipient and/or frank shock and/or unstable (and thus a higher risk patient) and required same-setting multivessel PCI. Second, it is problematic to rigorously determine if the completed “strategy” for MVD PCI as grouped in each study was the strategy initially chosen or if clinical circumstances dictated deviating to another strategy. Only adequately powered randomized clinical trials will be able to ensure that patients randomized to each multivessel PCI strategy will indeed be comparable.
Decision making for revascularization for MVD during PPCI for STEMI is challenged by several considerations. First, there is legitimate concern that aggressive multivessel stenting in the setting of an initial STEMI occurs in a milieu of heightened inflammation and hypercoagulability. Support for this concept comes from multiple clinical trials evaluating the fate and time course of inflammatory markers released at the time of a myocardial infarction. Additionally, although not directly comparable, there is a higher rate of stent thrombosis in patients with STEMI compared with those undergoing stenting in the setting of stable coronary artery disease. Whether this phenomenon occurs at noninfarct stenosis remains uncertain. The absolute risk and time course of this heightened prothrombotic state also remain to be determined but may be additional factors influencing the apparent worse outcomes in single-procedure multivessel PCI for STEMI. Second, many of these cases are occurring off hours, when staffing and resources are less than what they are during regular hours. Taking a page from the chronic total occlusion playbook, where chronic total occlusions are not optimally performed as part of an ad hoc procedure, PCI of nonculprit vessels might best be deferred until full staffing and resources are available and after appropriate review of the case has occurred to optimize outcomes. Finally, using simple visual determination of the need to perform additional PCI, which is a common practice in the setting of a STEMI, runs contrary to current best practices. A substantial body of published research supports the use of physiological assessment of lesion severity to optimize outcomes in multivessel PCI, which may be pushed aside during a STEMI to simply “get the patient upstairs in the most expeditious manner possible.” Fractional flow reserve of nonculprit lesions (but not PCI) after primary PCI of the infarct vessel to guide later staged revascularization is appealing, but it remains to be rigorously tested in clinical trials.
How should we use the observations of this trial to guide our practice? The 2014 European Society of Cardiology guidelines for STEMI supported infarct-only PCI during the index procedure, with the exception of patients with unstable or cardiogenic shock (6). In contrast, the 2015 revision of the American College of Cardiology and American Heart Association STEMI guidelines moved multivessel PCI during STEMI from a class III indication to a class IIb recommendation in light of recent randomized clinical trials suggesting that more complete and earlier revascularization in patients with MVD and STEMI may be more beneficial than infarct-only PPCI (7). The study of Tarantini et al. (5) supports the recent American College of Cardiology and American Heart Association recommendation to allow broader consideration of earlier and more complete revascularization in patients with MVD and STEMI. The question remaining to be answered by appropriately designed and powered clinical trials is when, not whether, complete revascularization should be performed.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Applegate has reported that he has no relationships relevant to the contents of this paper to disclose.
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