Study Overview
Objective. To determine the prognostic impact of multivessel percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) multivessel disease presenting with cardiogenic shock.
Design. Retrospective study using the nationwide, multicenter, prospective KAMIR-NIH (Korea Acute Myocardial Infarction-National Institutes of Health) registry.
Setting and participants. Among the 13,104 patients enrolled in the KAMIR-NIH registry, 659 patients with STEMI with multivessel disease presenting with cardiogenic shock who underwent primary PCI were selected.
Main outcome measures. The primary outcome was all-cause death at 1 year. Secondary outcomes included patient-oriented composite outcome (composite of all-cause death, any myocardial infarction, and any repeat revascularization) and its individual components.
Main results. A total of 260 patients were treated with multivessel PCI and 399 patients were treated with infarct-related artery (IRA) PCI only. The risk of all-cause death was significantly lower in the multivessel PCI group (21.3% vs 31.7%; hazard ratio [HR] 0.59, 95% CI 0.43–0.82, P = 0.001). Non-IRA repeat revascularization was significantly lower in the multivessel group (6.7% vs 8.2%; HR 0.39, 95% CI 0.17–0.90, P = 0.028). In multivariate model, multivessel PCI was independently associated with reduced risk of 1-year all-cause death and patient-oriented composite outcome.
Conclusion. Among patients with STEMI and multivessel disease with cardiogenic shock, multivessel PCI was associated with significantly lower risk of all-cause death and non-IRA repeat revascularization.
Commentary
Historically, non-culprit vessel revascularization in the setting of acute myocardial infarction (AMI) was not routinely performed. However, recent trials have shown the benefit of non-culprit vessel revascularization in patients with hemodynamically stable AMI [1–3]. The result of these trials have led to upgrade in U.S. guideline recommendations for non-infarct-related artery PCI in hemodynamically stable patients presenting with AMI to Class IIb from Class III [4]. Whether these findings can be extended to hemodynamically unstable (cardiogenic shock) patients is controversial. Recently, results of a well-designed randomized control trial (CULPRIT-SHOCK) suggested worse outcome with immediate multivessel PCI in this population [5]. The composite endpoint of death and renal replacement therapy at 30 days was higher in the multivessel PCI at the time of primary PCI group compared to initial culprit lesion only group (55.9% vs 45.9%, P = 0.01). The composite endpoint was mainly driven by death (51.6% vs 43.3%, P = 0.03), and the rate of renal replacement therapy was numerically higher in the mutivessel PCI group (16.4% vs 11.6%, P = 0.07).
Lee et al investigated a similar clinical question using the nationwide, multicenter, prospective KAMIR-NIH registry data [6]. In this study, the primary endpoint of all cause death occurred in 53 of the 260 patients (21.3%) in the multivessel PCI group and 126 of the 399 patients (31.7%) in the IRA-only PCI group (relative risk [RR] 0.59, 95% CI 0.43–0.82, P = 0.001). Similarly, the multivessel PCI group had lower non-IRA repeat revascularization (RR 0.39, 95% CI 0.17-0.90, P = 0.028) and lower patient-oriented composite outcome (all-cause death, any myocardial infarction, or any repeat revascularization) (RR 0.58, 95% CI 0.44–0.77, P < 0.001). These results remained similar after multivariate adjustment, propensity matching, and inverse probability weighted analysis.
The discrepancy of the results of the KAMIR study compared to CULPRIT-SHOCK is likely related to the difference in the design of the two studies. First, CUPRIT-SHOCK compared multivessel revascularization during index primary PCI to culprit-only revascularization strategy with staged revascularization if necessary. There were 9.4% randomized to multivessel PCI who crossed over to IRA-only PCI and 17.4% randomized to IRA-only PCI who crossed over to multivessel PCI during the index hospitalization. In contrast, the KAMIR registry compared patients who underwent IRA-only PCI to multivessel PCI, which included those who had immediate revascularization during the primary PCI and those who had staged revascularization during the index hospitalization. Therefore, multivessel PCI is defined very differently in both studies and cannot be considered equivalent.
Second, CULPRIT-SHOCK was a prospective randomized control study and KAMIR was an observational study analyzing data from a prospectively collected large database. Although multiple statistical adjustments were performed, this observational nature of the study is subject to selection bias and other unmeasured biases such as frailty assessment.
Third, the timing of the revascularization was different between two studies. In CULPRIT-SHOCK, immediate revascularization of non-IRA was achieved in 90.6% of patients in the multivessel PCI group. On the other hand, only 60.4% of patients of multivessel PCI group in KAMIR study underwent immediate revascularization of the non-IRA and 39.6 % of patients underwent staged procedure. This leads to significant survival bias, since these 39.6% of patients survived the initial event to be able to undergo the staged procedure. Patients who had planned staged intervention but could not survive were included in the IRA-only PCI group.
Fourth, there may be difference in the severity of the patient population included in the analysis. In the CULPRIT-SHOCK trial, a significant non-IRA was defined as > 70% stenosis, and all chronic total occlusions (CTO) were attempted in the multivessel PCI group according to trial protocol. In CULPRIT-SHOCK, 23% of patient had one or more CTO lesions. In the KAMIR registry, a significant non-IRA was defined as > 50% stenosis of the non-culprit vessel and CTO vessels were not accounted for. Although CTO intervention improves angina and ejection fraction [7,8], whether CTO intervention has mortality benefit needs further investigation. In a recent EXPLORE trial, the feasibility and safety of intervention of chronic total occlusion in non-infarct-related artery in STEMI population was established [8]. However, only hemodynamically stable patients were included in the study and all CTO interventions were performed in staged fashion (5 ± 2 days after index procedure) [8]. There is a possibility of attempting CTO PCI in this acute setting caused more harm than benefit.
Finally, in order to be enrolled in the CULPRIT-SHOCK trial, patients needed to meet stringent criteria for cardiogenic shock. In KAMIR study, this data was retrospectively determined and individual components used to define cardiogenic shock were not available. This difference may have led to inclusion of more stable patients as evidenced by lower mortality rate in KAMIR study compared to CULPRIT-SHOCK (51.6% mortality for multivessel PCI in CULPRIT-SHOCK and 21.3% mortality for multivessel PCI patients in KAMIR study). CULPRIT-SHOCK trial had a high rate of mechanical ventilation (~80%), requirement of catecholamine support (~90%), and long ICU stays (median 5 days). This information is not reported in the KAMIR study.
Considering above differences in the study design, the evidence level for CULPRIT-SHOCK appears to be stronger compared to the KAMIR study, which should be considered as hypothesis-generating as all other observational studies. However, the KAMIR study is still an important study suggesting possible benefit of multivessel PCI in patients presenting with ST elevation myocardial infarction and cardiogenic shock. This leads us to an answered question whether staged multivessel intervention or less aggressive multivessel intervention (not attempting CTO) is a better option in this population.