Efficacy of Statin Treatment According to Baseline Renal Function in Korean Patients with Acute Myocardial Infarction Not Requiring Dialysis Undergoing Newer-Generation Drug-Eluting Stent Implantation

We investigated the 2-year efficacy of statin treatment according to baseline renal function in patients with acute myocardial infarction (AMI) not requiring dialysis undergoing newer-generation drug-eluting stent (DES) implantation. A total of 18,875 AMI patients were classified into group A (statin users, n = 16,055) and group B (statin nonusers, n = 2820). According to the baseline estimated glomerular filtration rate (eGFR; ≥90, 60–89, 30–59 and <30 mL/min/1.73 m2), these two groups were sub-classified into groups A1, A2, A3 and A4 and groups B1, B2, B3 and B4. The major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI) and any repeat revascularization, were evaluated. The MACE (group A1 vs. B1, p = 0.002; group A2 vs. B2, p = 0.007; group A3 vs. B3, p < 0.001; group A4 vs. B4, p < 0.001), all-cause death (p = 0.006, p < 0.001, p < 0.001, p < 0.001, respectively) and cardiac death (p = 0.004, p < 0.001, p < 0.001, p < 0.001, respectively) rates were significantly higher in statin nonusers than those in statin users. Despite the beneficial effects of statin treatment, the MACE (group A1 vs. A2 vs. A3 vs. A4: 5.2%, 6.4%, 10.1% and 18.5%, respectively), all-cause mortality (0.9%, 1.8%, 4.6% and 12.9%, respectively) and cardiac death (0.4%, 1.0%, 2.6% and 6.8%, respectively) rates were significantly increased as eGFR decreased in group A. These results may be related to the peculiar characteristics of chronic kidney disease, including increased vascular calcification and traditional or nontraditional cardiovascular risk factors. In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function.


Introduction
During the past two decades, rapid coronary reperfusion and revascularization with newer antiplatelet and anticoagulation therapies have improved the survival of patients with acute myocardial infarction (AMI) [1,2]. Ischemic heart disease accounts for almost 1.8 million annual deaths, or 20% of all deaths in Europe [3]. Similar to Western countries, AMI continues to be a major cause of mortality in the Asia-Pacific population [4]. Statin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, has both fundamental lipid-lowering capacity and additional pleiotropic effects on reducing morbidity and mortality [5,6]. The current guidelines recommend that statin therapy should be initiated or continued in all patients with AMI if there are no contraindications to its use [7,8]. Every 30% decrease in glomerular filtration rate (GFR) was associated with a 29% increase in the risk of a major vascular event (MVE) [9]. Hence, individuals with chronic kidney disease (CKD) grade 3a to 4 (GFR: 15-59 mL/min/1.73 m 2 ) have a 2-or 3-fold increased risk of cardiovascular mortality compared with those without CKD [10]. Some suggested mechanisms for the progression of CKD in patients with cardiovascular and renal diseases include endothelial dysfunction, oxidative stress and systemic inflammation of the glomerular capillary wall [11]. Statins alleviate many adverse effects of reduced nitric oxide availability in the inflammatory environment and improve endothelial function [12]. Moreover, statin treatment has been considered a mainstay strategy for CKD patients with respect to reducing the all-cause mortality [13]. Although previous reports [14][15][16] showed that statin treatment reduced the risk of major adverse events in patients with CKD, there are some debates [17]. Additionally, their study population [14][15][16][17] was not confined to patients with AMI. Kim et al. [18,19] showed that stent generation could be regarded as an important determinant of major adverse cardiac events (MACE) in patients with STsegment elevation myocardial infarction (STEMI) and AMI. Therefore, we believe that the presence or absence of beneficial effects of statin treatment on major adverse events should be re-estimated in patients with AMI according to renal function under the current newergeneration drug-eluting stent (DES) era to provide more accurate real-world information to interventional cardiologists. Hence, in this study, we evaluated the 2-year efficacy of statin treatment according to baseline renal function in patients with AMI undergoing newer-generation DES implantation.

Study Population
The study population was recruited from the Korea AMI Registry (KAMIR) [4]. Details of this registry can be found on the KAMIR website (http://www.kamir.or.kr (accessed on 15 April 2021). All patients aged ≥18 years at the time of hospital admission were included. The KAMIR was established in November 2005 and involved more than 50 communities and teaching hospitals in South Korea. A total of 45,555 patients with AMI who underwent successful stent implantation and who were not receiving continuous renal replacement therapy including hemodialysis or peritoneal dialysis between January 2006 and June 2015 were eligible for inclusion in this study. Patients with the following were also excluded: deployed bare-metal stents (n = 2362, 5.2%) and first-generation DES (n = 11,166, 24.5%), incomplete laboratory results (n = 8330, 18.3%), loss to follow-up (n = 2247, 4.9%), post-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade <3 (n = 2089, 4.6%), in-hospital death (n = 447, 1.0%) and treatment with other kinds of statins, except for atorvastatin, rosuvastatin, simvastatin, pitavastatin, pravastatin and fluvastatin (n = 39, 0.09%). Thus, a total of 18,875 AMI patients who underwent successful PCI with a newer-generation DES were included. The types of new-generation DESs used are listed in Table 1. Among the AMI patients, 16,055 (85.1%) were classified into group A (statin users) and 2820 (15.0%) into group B (statin nonusers). Thereafter, groups A and B were further subclassified into groups A1 and B1 (eGFR ≥ 90 mL/min/1.73 m 2 , n = 6847 (42.6%) and n = 889 (31.5%), respectively), groups A2 and B2 (eGFR 60-89 mL/min/1.73 m 2 , n = 6557 (40.8%) and n = 1227 (43.5%), respectively), groups A3 and B3 (eGFR 30-59 mL/min/1.73 m 2 , n = 2144 (13.4%) and n = 537 (19.0%), respectively) and groups A4 and B4 (eGFR < 30 mL/min/1.73 m 2 , n = 507 (3.2%) and n = 167 (5.9%), respectively) according to their baseline renal function and strata used to define CKD stages (Figure 1) [20]. However, because the number of patients included in stages 4 and 5 was small, they were grouped into one group (A4 or B4) in our study. The detailed reasons for not using statins in group B were as follows: (1) expected risk was higher than the benefit due to several etiologic factors such as end-stage renal failure, advanced age ≥75 years or severe heart failure (HF) (n = 1213, 43.0%), (2) abnormal liver function (aspartate aminotransferase or alanine aminotransferase was higher than 3-fold the upper normal limit) (n = 689, 24.4%), (3) multi-organ failure (n = 121, 4.3%), (4) statininduced myopathy or arthralgia (n = 110, 3.9%) and (5) unknown (n = 687, 24.4%). All data were collected using a web-based case report form at each participating center. The study was conducted in accordance with the ethical guidelines of the 2004 Declaration of Helsinki and was approved by the ethics committee at each participating center and the Chonnam National University Hospital Institutional Review Board ethics committee (CNUH-2011-172). All 18,875 patients included in the study provided written informed consent prior to enrollment. They also completed a 2-year clinical follow-up through face-to-face interviews, phone calls or chart reviews. All clinical events were evaluated by an independent event adjudication committee. The event adjudication process was previously described by the KAMIR investigators. [21].

Percutaneous Coronary Intervention (PCI) Procedure and Medical Treatment
Coronary angiography and PCI were performed via a transfemoral or transradial approach in accordance with the general guidelines [22]. Aspirin (200-300 mg) and clopidogrel (300-600 mg) when available, or alternatively, ticagrelor (180 mg) or prasugrel (60 mg), were prescribed as the loading doses to the individuals before PCI. After PCI, dual antiplatelet therapy (DAPT; a combination of aspirin (100 mg/day) with clopidogrel (75 mg/day) or ticagrelor (90 mg twice a day) or prasugrel (5-10 mg/day)) was recommended for more than 12 months. Based on previous reports [23,24], triple antiplatelet therapy was administered (TAPT; 100 mg of cilostazol administered twice a day in addition to DAPT) at the discretion of the individual operator. In this study, the patients who received atorvastatin, rosuvastatin, simvastatin, pitavastatin, pravastatin and fluvastatin were included (Table 1) and the type and dose of statins to be used were left to the physicians' discretion.

Study Definitions and Clinical Outcomes
AMI was defined according to the current guidelines [7,8]. A successful PCI was defined as a residual stenosis of <30% and TIMI flow grade 3 in the infarct-related artery (IRA). Glomerular function was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for eGFR [25]. The major clinical endpoint was the occurrence of MACE, defined as all-cause mortality, recurrent myocardial infarction (re-MI) or any repeat coronary revascularization, including target lesion revascularization (TLR), target vessel revascularization (TVR) and non-TVR during the follow-up period. All-cause mortality was considered cardiac death (CD) unless an undisputed noncardiac cause was present [26].

Statistical Analysis
Differences in the continuous variables among the four groups were evaluated using analysis of variance or the Jonckheere-Terpstra test, and a post hoc analysis was performed using the Hochberg test or Dunnett's T3 test; data are presented as means ± standard deviations. For discrete variables, differences between two of the four or eight groups were analyzed using the chi-square or Fisher's exact test, as deemed appropriate, and data are presented as counts and percentages. We tested all variables in the univariate analysis (p < 0.05) (Table S1). After univariate analysis, we tested all variables with p < 0.001 in the multivariate Cox regression analysis, which are listed as follows: male sex, age, left ventricular ejection fraction (LVEF), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiogenic shock, cardiopulmonary resuscitation (CPR) on admission, Killip class III/IV, STEMI, hypertension, diabetes mellitus (DM), previous MI, previous PCI, previous HF, previous cerebrovascular accident (CVA), current smoker, N-terminal pro-brain natriuretic peptide (NT-ProBNP), blood glucose level, total cholesterol level, triglyceride level, low-density lipoprotein (LDL) cholesterol level, high-density lipoprotein (HDL) cholesterol level, use of aspirin, use of angiotensin-converting enzyme inhibitor (ACEI), use of beta blockers (BBs), left main coronary artery (LM) infarct-related artery (IRA) and treated vessel, single-vessel disease, ≥3-vessel disease, stent diameter, stent length and number of stents. Various clinical outcomes were estimated using Kaplan-Meier curve analysis, and group differences were compared using the log-rank test. A two-tailed p value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS software v20 (IBM; Armonk, NY, USA).

Baseline Characteristics
Tables 1-4 show the baseline, laboratory, angiographic and procedural characteristics of the study population.

Group A (Statin Users)
Group A1 (eGFR ≥ 90 mL/min/1.73 m 2 ) included the highest number of male patients; patients who received PCI within 24 h; current smokers; those with left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCx) as the IRA and treated vessels, American College of Cardiology/American Heart Association (ACC/AHA) type B2 lesion, single-vessel disease and biolimus-eluting stent (BES) as the deployed stent; those who used optical coherence tomography and fraction flow reserve; and those prescribed with aspirin, ticagrelor, prasugrel, ACEI, BB and rosuvastatin as the discharge medications. The mean levels of LVEF, BMI, SBP, DBP, total cholesterol, triglyceride and LDL cholesterol and the mean diameter of deployed stents were highest in group A1. In group A2 (eGFR 60-89 mL/min/1.73 m 2 ), the number of patients with STEMI and pre-PCI TIMI 0/1 and the mean levels of peak creatine kinase myocardial band (CK-MB) and HDL cholesterol were highest. In group A3 (eGFR 30-59 mL/min/1.73 m 2 ), including patients who required CPR on admission, who received clopidogrel and cilostazol as the discharge medications, with the right coronary artery (RCA) as the IRA and treated vessel, with 2-vessel disease and with zotarolimus-eluting stent as a deployed stent, the mean age of the enrolled patients was highest. In group A4 (eGFR < 30 mL/min/1.73 m 2 ), including patients with cardiogenic shock, Killip class III/IV, non-STEMI (NSTEMI), hypertension, DM, previous MI, previous PCI, previous coronary artery bypass graft (CABG), previous HF, previous CVA, LM IRA and treated vessel, ACC/AHA type C lesion, ≥3-vessel disease, everolimuseluting stent as a deployed stent and atorvastatin as a discharge medication, the mean values of peak troponin-I, NT-ProBNP, high-sensitivity C-reactive protein (hs-CRP), blood glucose and stent length and mean number of deployed stents were highest.

Group B (Statin Nonusers)
Group B1 (eGFR ≥ 90 mL/min/1.73 m 2 ) included the highest number of male patients, patients who received PCI within 24 h, current smokers and patients with LAD and LCx as the IRA and treated vessels, single-vessel disease, BES as a deployed stent and aspirin, prasugrel and ACEI as the discharge medications. The mean levels of LVEF, BMI, SBP, DBP, total cholesterol, triglyceride and LDL cholesterol and the mean diameter of deployed stents were highest in group B1. In group B2 (eGFR 60-89 mL/min/1.73 m 2 ), including patients with STEMI, ACC/AHA type B1 lesion and pre-PCI TIMI 0/1, the mean levels of peak CK-MB and HDL cholesterol and the prescription rates of clopidogrel and BB as the discharge medications were highest. In group B3 (eGFR 30-59 mL/min/1.73 m 2 ), including patients who needed CPR on admission and those with previous CABG, RCA as the IRA and treated vessel and 2-vessel disease, the mean age of enrolled patients and mean number of deployed stents were highest. In group B4 (eGFR < 30 mL/min/1.73 m 2 ), including patients with cardiogenic shock, Killip class III/IV, NSTEMI, hypertension, DM, previous MI, previous PCI, previous CABG, previous HF, previous CVA, LM IRA and treated vessel, ACC/AHA type C lesion, ≥3-vessel disease, everolimus-eluting stent as a deployed stent and atorvastatin as a discharge medication, the mean values of peak troponin-I, NT-ProBNP, hs-CRP, blood glucose, stent length and mean number of deployed stents were highest.

Clinical Outcomes
The 2-year major clinical outcomes are summarized in Table 5 and Table S2 and Figure 2.

Discussion
The main findings of this retrospective observational study including patients with AMI who underwent successful PCI with newer-generation DES implantation were as follows: (1) regardless of the baseline renal function, individuals who underwent statin treatment had reduced rates of MACE, all-cause mortality and CD than those in statin nonusers; (2) despite these beneficial effects of statin therapy, the MACE, all-cause death and CD rates were significantly increased as the baseline eGFR decreased; (3) older age, STEMI, reduced LVEF, cardiogenic shock, CPR on admission, NT-ProBNP, LDL cholesterol, ACEI levels, ≥3-vessel disease and LM (IRA) were common independent predictors for both MACE and all-cause mortality in the statin user group.
To date, in the current guidelines [7,8], despite an MVE reducing the benefit of statin therapy in predialysis patients, this beneficial effect of statin therapy was not distinguished according to renal function (e.g., CKD grade 3, 4, or 5), and there is no convincing evidence among patients on dialysis [10]. In our study, we only included patients with AMI who did not require dialysis. Additionally, we directly compared major clinical outcomes between the statin user and nonuser groups according to baseline renal function to evaluate the presence or absence of benefit of statin treatment in these different renal function groups. In Table 6, in all four groups (eGFR ≥ 90, 60-89, 30-59 and <30 mL/min/1.73 m 2 ), statin therapy significantly reduced the rates of MACE, all-cause mortality and CD compared with those in statin nonusers. Moreover, the rates of MACE, all-cause mortality and CD significantly increased as the baseline eGFR decreased in group A (Table 5). These findings could be related to the poorer baseline characteristics of the statin nonuser group (e.g., reduced LVEF, high numbers of patients with cardiogenic shock or CPR on admission and high mean level of NT-ProBNP; Tables 3 and 4) compared with statin users. However, our results were consistent with those of previous reports [15,27,28]. Palmer et al. [15] showed that statins reduced the all-cause mortality (relative risk (RR), 0.81; 95% CI, 0.74-1.88) and CD (RR, 0.78; 95% CI, 0.68-0.89) rates compared with placebo or no treatment in individuals not receiving dialysis. Sarnak et al. [10] also mentioned that the benefit of reducing MVE with statin-based therapy decreases as eGFR declines. Similarly, Herrington et al. [14] demonstrated that smaller relative effects of MVE were observed as eGFR declined (RR, 0.78; 99% CI, 0.75-0.82 for eGFR ≥ 60 mL/min/1.73 m 2 ; RR, 0.76; 99% CI, 0.70-0.81 for eGFR 45-60 mL/min/1.73 m 2 ; RR, 0.85; 99% CI, 0.75-0.96 for eGFR 30 to <45 mL/min/1.73 m 2 ; RR, 0.85; 95% CI, 0.71-1.02 for eGFR <30 mL/min/1.73 m 2 ). In group B, the MACE rates between groups B1 and B3 and between groups B2 and B3 and all-cause mortality and CD rates between groups B1 and B2 and between groups B2 and B3 were not significantly different (Table S2). However, after statin treatment (group A), the rates of MACE between groups A1 and A3 (aHR, 1.465; p < 0.001) and groups A2 and A3 (aHR, 1.249; p = 0.026) and all-cause mortality and CD rates between groups A1 and A3 (aHR, 3.691; p < 0.001, aHR, 3.429; p < 0.001, respectively) and between groups A2 and A3 (aHR, 1.843; p < 0.001, aHR, 1.647; p = 0.019, respectively) were significantly different. These results could reflect the trend that if GFR is reduced, the relative beneficial effects of statins might be smaller, in accordance with previous reports. [10,14]. Although the precise mechanisms responsible for the pattern of diminished benefit of statin with lower renal function are not well-known, the peculiar characteristics of the patients with CKD could be related to this pattern [14]. Patients with CKD are often excluded from randomized trials that evaluate cardioprotective drugs, and the quality and coverage of evidence on which to guide decision making in this population is suboptimal [29]. This lack of evidence on optimal treatment strategies for such patients may result in worse outcomes [30]. Additionally, the cause of CD is influenced by misclassification of their atypical clinical presentation [31]. The difficulty of interpreting elevated levels of biomarkers of cardiac damage in CKD is a possible contributing factor [32]. As the GFR declines, vascular calcification increases, and the calcification of the intima and media of large vessels in CKD is associated with all-cause death and cardiovascular mortality [10,33,34]. These cardiovascular changes in CKD are related to traditional (e.g., diabetes and hypertension) and nontraditional CKD-related cardiovascular disease risk factors (e.g., mineral and bone disease abnormalities, inflammation and oxidative stress) [10]. Because there is geographical variation in the prevalence of DM, the absolute magnitude of beneficial effects of statin therapy can vary regionally [35].
In our study, the re-MI and any repeat revascularization rates were not significantly different between the statin user and nonuser groups. Similar results were reported by Natsuaki et al. [36]. Among 14,706 patients who underwent PCI [36], the number of patients with AMI was approximately 30%. During a median follow-up of 956 days, the re-MI and any repeat revascularization rates were not significantly different between the statin user and nonuser groups according to the three different renal function groups (eGFR ≥ 60, ≤30 to <60 and <30 mL/min/1.73 m 2 ). They [36] suggested that patients with advanced CKD (eGFR < 30 mL/min/1.73 m 2 ) generally have advanced atherosclerosis, typically characterized by heavy calcification, and statins may no longer provide significant benefits in patients with end-stage vascular pathology. Another randomized study [37] failed to show the effects of statin therapy in decreasing restenosis. Although the study population was not confined to individuals with AMI or CKD, according to the Cholesterol Treatment Trialists' (CTT) Collaboration report, intensive statin therapy reduced the coronary revascularization rate by about 19% (95% CI, 11-18; p < 0.0001) [38]. Walter et al. [39] found that patients receiving prolonged statin treatment developed lower in-stent restenosis rates in comparison with nonreceivers (25% vs. 38%). Therefore, our results showing similar re-MI and any repeat revascularization rates between statin users and nonusers could be related to low number of enrolled patients in groups A4, B1, B3 and B4 and relatively low incidences of these events compared with previous studies [17,30]. According to recent meta-analysis data that evaluated CKD patients [40], in which CKD was defined as eGFR < 60 mL/min/1.73 m 2 , results showed that the TLR/TVR (RR, 0.69; 95% CI, 0.57-0.84) was significantly reduced with DESs compared with bare-metal stents (BMS). Additionally, the use of second-generation DESs were associated with relative 27% reduction in TLR/TVR compared with first-generation DESs. Another study's metaanalysis data [41] showed that DESs were associated with lower TVR (RR, 0.61; 95% CI, 0.47-0.80) when compared with BMSs in patients with CKD. However, we think that future studies specifically focused on advanced CKD may help to clarify the benefit of statin treatment after PCI in this group. Interestingly, the number of patients with NSTEI was increased as their renal function deteriorated (Tables 1 and 2). Although, the precise underlying mechanisms of this phenomenon are not well known, some suggest that plaque erosion may be more predominant in the CKD group, in those patients who tend to be older and in those who have more established atherosclerosis, whereas the incidence of plaque rupture may be more common in younger non-CKD patients in whom less mature plaques are more vulnerable to rupture [42,43]. In both the statin user and nonuser groups, reduced LVEF, cardiogenic shock, CPR on admission and NT-ProBNP and LDL cholesterol levels were common independent predictors for both MACE and all-cause mortality. These variables are well-known unfavorable risk factors for mortality in patients with AMI [7,8].
Because the study populations of previous studies [14][15][16][17]27,28,36] regarding the long-term effects of statin treatment on major adverse events in patients with CKD were not confined to individuals with AMI and who received newer-generation DESs, we investigated the long-term major clinical outcomes of statin therapy confined to those patients to reflect current real-world practice. Moreover, as mentioned [29], evidence on optimal treatment strategies in patients with CKD is not abundant. More than 50 highvolume universities or community hospitals in South Korea participated in this study, but the study population was insufficient to provide meaningful results. Despite this weak point, we believe that our results could provide helpful information to interventional cardiologists in terms of current real-world information showing long-term effects of statin treatment according to the different renal function groups.
This study had other limitations. First, there may have been some underreporting and/or missing data and selection bias because this was a nonrandomized study. Second, although microalbuminuria is an early marker of chronic renal damage and a risk factor of cardiovascular disease [44], there was likely some misclassification of study groups due to the lack of information concerning the total amount of proteinuria and the presence or absence of microalbuminuria. Third, the estimation of renal function was based on a single measurement of eGFR at the time of presentation to the hospital. However, there is a possibility that eGFR may have worsened during the follow-up period. Unfortunately, we could not provide follow-up eGFR values because of a limitation of these registry data. Fourth, according to the current guidelines [7], the treatment goal is an LDL cholesterol level <1.8 mmol/L (<70 mg/dL) or at least 50% reduction in LDL cholesterol if the baseline LDL cholesterol level is 1.8-3.5 mmol/L. However, information regarding the follow-up levels of blood LDL cholesterol was incomplete in our registry data. This is a major shortcoming of this study and may be an important bias. Fifth, because the registry data did not include detailed or complete data on prescription doses, long-term adherence, discontinuation and drug-related adverse events, we could not provide this information during the follow-up period, which could have caused bias. Sixth, despite multivariable analyses, the variables that were not included in the data registry might have affected the study outcome. Seventh, because statins have a longer duration of use, the 2-year follow-up period in this study was relatively short for estimating long-term clinical outcomes. Eighth, because this retrospective study enrolled patients who underwent PCI between January 2006 and June 2015, this broad timeframe could have affected the clinical outcomes. Finally, during a 2-year follow-period, patients experienced definite or probable stent thrombosis (ST). Both in group A (group A1 vs. A2 vs. A3 vs. A4 = 37/6847 (0.5%) vs. 46/6557 (0.7%) vs. 22/2144 (1.0%) vs. 5/507 (1.0%), p = 0.091) and B (9/889 (1.0%) vs. 7/1227 (0.6%) vs. 4/537 (0.7%) vs. 4/537 (0.7%) vs. 1/167 (0.6%), p = 0.702, respectively), the cumulative incidences of ST were very low. Therefore, although ST is an important major determinant variable in patients with AMI [18], we inevitably could not include this variable as an endpoint in our study.

Conclusions
In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function in patients with AMI who underwent successful PCI. These results could be helpful in understanding the current real-world effects of statins on patients with AMI with different renal functions. However, more large-scale, long-term follow-up studies are warranted to confirm these results.