Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

BACKGROUND: A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. METHODS: Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. RESULTS: SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). CONCLUSION: Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

Clinical outcomes of adjusted-dose versus standard-dose prasugrel in East Asian patients with acute myocardial infarction.

BACKGROUND: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. METHODS: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. RESULTS: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000). CONCLUSIONS: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.

Very early vs delayed invasive strategy in high-risk NSTEMI patients without hemodynamic instability: Insight from the KAMIR-NIH.

BACKGROUND: High-risk non-ST-elevation myocardial infarction (NSTEMI) patients' optimal timing for percutaneous coronary intervention (PCI) is debated despite the recommendation for early invasive revascularization. This study aimed to compare outcomes of NSTEMI patients without hemodynamic instability undergoing very early invasive strategy (VEIS, ≤ 12 hours) versus delayed invasive strategy (DIS, >12 hours). METHODS: Excluding urgent indications for PCI including initial systolic blood pressure under 90 mmHg, ventricular arrhythmia, or Killip class IV, 4,733 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Patients were divided into low and high- global registry of acute coronary events risk score risk score (GRS) groups based on 140. Both groups were then categorized into VEIS and DIS. Clinical outcomes, including all-cause death (ACD), cardiac death (CD), recurrent MI, and cerebrovascular accident at 12 months, were evaluated. RESULTS: Among 4,733 NSTEMI patients, 62% had low GRS, and 38% had high GRS. The proportions of VEIS and DIS were 43% vs. 57% in the low GRS group and 47% vs. 53% in the high GRS group. In the low GRS group, VEIS and DIS demonstrated similar outcomes; however, in the high GRS group, VEIS exhibited worse ACD outcomes compared to DIS (HR = 1.46, P = 0.003). The adverse effect of VEIS was consistent with propensity score matched analysis (HR = 1.34, P = 0.042). CONCLUSION: VEIS yielded worse outcomes than DIS in high-risk NSTEMI patients without hemodynamic instability in real-world practice.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention for acute myocardial infarction with cardiogenic shock.

The benefits of intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) in the clinical context of cardiogenic shock (CS) complicating acute myocardial infarction are lacking. We aimed to investigate the impact of IVUS-guided PCI in patients with AMI and CS. From the pooled data based on a series of Korean AMI registries during 2011-2020, we identified 1418 consecutive patients who underwent PCI with second generation drug-eluting stent (DES) for AMI and CS. The primary endpoint was the 1-year rate of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, and ischemic-driven target lesion revascularization. In total, 294 (20.7%) and 1124 (79.3%) underwent IVUS-guided and angiography-guided PCI with second generation DES implantation, respectively. The 1-year TLF was not significantly different between groups after IPTW analysis (hazard ratio 0.93, 95% confidence interval 0.65-1.34, p = 0.70). Additionally, the adjusted landmark analysis for TLF at 30 days and between 30 days and 1 year after PCI demonstrated no significant difference between the groups. In conclusion, in patients with AMI and CS who underwent PCI with second-generation DES, IVUS-guided PCI did not improve the 1-year TLF compared with angiography-guided PCI.Registration: URL:  http://cris.nih.go.kr . KCT0000863 and KCT0008355.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).Methods and Results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Prediction of longitudinal clinical outcomes after acute myocardial infarction using a dynamic machine learning algorithm.

Several regression-based models for predicting outcomes after acute myocardial infarction (AMI) have been developed. However, prediction models that encompass diverse patient-related factors over time are limited. This study aimed to develop a machine learning-based model to predict longitudinal outcomes after AMI. This study was based on a nationwide prospective registry of AMI in Korea (n = 13,104). Seventy-seven predictor candidates from prehospitalization to 1 year of follow-up were included, and six machine learning approaches were analyzed. Primary outcome was defined as 1-year all-cause death. Secondary outcomes included all-cause deaths, cardiovascular deaths, and major adverse cardiovascular event (MACE) at the 1-year and 3-year follow-ups. Random forest resulted best performance in predicting the primary outcome, exhibiting a 99.6% accuracy along with an area under the receiver-operating characteristic curve of 0.874. Top 10 predictors for the primary outcome included peak troponin-I (variable importance value = 0.048), in-hospital duration (0.047), total cholesterol (0.047), maintenance of antiplatelet at 1 year (0.045), coronary lesion classification (0.043), N-terminal pro-brain natriuretic peptide levels (0.039), body mass index (BMI) (0.037), door-to-balloon time (0.035), vascular approach (0.033), and use of glycoprotein IIb/IIIa inhibitor (0.032). Notably, BMI was identified as one of the most important predictors of major outcomes after AMI. BMI revealed distinct effects on each outcome, highlighting a U-shaped influence on 1-year and 3-year MACE and 3-year all-cause death. Diverse time-dependent variables from prehospitalization to the postdischarge period influenced the major outcomes after AMI. Understanding the complexity and dynamic associations of risk factors may facilitate clinical interventions in patients with AMI.

Empagliflozin after Acute Myocardial Infarction.

BACKGROUND: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown. METHODS: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis. RESULTS: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups. CONCLUSIONS: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.).

Intravascular imaging-guided percutaneous coronary intervention in patients with acute myocardial infarction and cardiogenic shock.

INTRODUCTION AND OBJECTIVES: There are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock. METHODS: Among a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis. RESULTS: Among the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88). CONCLUSIONS: In AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death.

Timing of fractional flow reserve-guided complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel disease: Rationale and design of the OPTION-STEMI trial.

BACKGROUND: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. METHODS: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. CONCLUSIONS: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.

Optimal timing of percutaneous coronary intervention for non-ST elevated myocardial infarction with congestive heart failure.

OBJECTIVES: This study investigated the optimal timing for percutaneous coronary intervention (PCI) in patients with NSTEMI complicated by heart failure (HF). METHODS: In total, 762 patients with NSTEMI and HF in a multicenter, prospective registry in South Korea were classified according to the Killip classification (Killip class 2, n = 414 and Killip class 3, n = 348) and underwent early (within 24 h) and delayed (after 24 h) PCI. The primary outcome was all-cause mortality which was further analyzed with landmark analysis with two months as a cut-off. Secondary outcomes were cardiovascular death, in-hospital cardiogenic shock (CS), readmission due to HF, and acute myocardial infarction during follow-up. RESULTS: Delayed PCI was associated with lower rates of 2-month mortality (6.1 % vs. 15.8 %, p = 0.007) and in-hospital CS (4.3 % vs. 14.1 %, p = 0.003), along with lower risks of 2-month mortality (hazard ratio [HR] = 0.38, 95 % confidence interval [CI] = 0.18-0.83, p = 0.014), in-hospital CS (HR = 0.29, 95 % CI = 0.12-0.71, p = 0.006) in multivariate Cox models of Killip class 3 patients. There was no statistical difference of incidence and risk of all predefined outcomes according to varying timing of PCI in Killip 2 patients. CONCLUSIONS: Based on these results, the timing of PCI in patients with NSTEMI complicated by HF should be determined based on HF severity. Delayed PCI should be considered in patients with NSTEMI and more severe HF.

Effect of hemoglobin A1c change on 24-month clinical outcomes in patients with diabetes after acute myocardial infarction.

BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes (n = 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1c > 1%, changes in HbA1c within 1%, and an increase in HbA1c > 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55 ±â€…0.85, 7.00 ±â€…0.98 and 7.07 ±â€…1.05 (P = 0.001) and HbA1c levels after 1 year were 6.62 ±â€…0.73, 7.05 ±â€…0.98 and 9.26 ±â€…1.59 (P = 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. METHODS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. RESULTS: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). CONCLUSIONS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). OBJECTIVES: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. METHODS: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. RESULTS: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. CONCLUSIONS: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).

Three-Year Clinical Outcomes With the Cilotax Dual Drug-Eluting Stent vs Everolimus-Eluting Stents in Patients With Acute Myocardial Infarction.

BACKGROUND: This study compared the safety and effectiveness of paclitaxel/cilostazol-eluting Cilotax stents with those of everolimus-eluting stents in patients with acute myocardial infarction. Real-world data from the Korea Acute Myocardial Infarction Registry were examined. METHODS: A total of 5,472 patients with acute myocardial infarction underwent percutaneous coronary intervention with Cilotax stents (n = 212) or everolimus-eluting stents (n = 5,260). The primary end point was the 3-year rate of target lesion failure. The other end points were major adverse cardiovascular events (a composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization), target vessel revascularization, and stent thrombosis. A propensity score matching analysis was performed to adjust for potential confounders by using a logistic regression model; propensity score matching generated 2 well-balanced groups (Cilotax group, n = 180; everolimus-eluting stents group, n = 170; N = 350). After propensity score matching, baseline clinical characteristics were similar between the groups. RESULTS: After percutaneous coronary intervention, compared with the everolimus-eluting stents group, the Cilotax group more often had major adverse cardiovascular events (24.1% vs 18.5%; P = .042), myocardial infarction (8.0% vs 3.2%; P < .001), target lesion revascularization (8.0% vs 2.6%; P < .001), target vessel revascularization (11.3% vs 4.5%; P < .001), and stent thrombosis (4.7% vs 0.5%; P < .001) before matching. Even after matching, the Cilotax group had more frequent target lesion revascularization (9.4% vs 2.9%; P = .22) and stent thrombosis (5.6% vs 1.2%; P = .34). CONCLUSION: In patients with acute myocardial infarction who underwent percutaneous coronary intervention, use of the Cilotax stent was associated with higher rates of target lesion revascularization, target vessel revascularization, and stent thrombosis than were everolimus-eluting stents. Use of the Cilotax dual drugeluting stent should be avoided in the treatment of myocardial infarction.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Association between body mass index and three-year outcome of acute myocardial infarction.

Body mass index (BMI), as an important risk factor related to metabolic disease. However, in some studies higher BMI was emphasized as a beneficial factor in the clinical course of patients after acute myocardial infarction (AMI) in a concept known as the "BMI paradox." The purpose of this study was to investigate how clinical outcomes of patients treated for AMI differed according to BMI levels. A total of 10,566 patients in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) from May 2010 to June 2015 were divided into three BMI groups (group 1: BMI < 22 kg/m2, group 2: ≥ 22 and < 26 kg/m2, and group 3: ≥ 26 kg/m2). The primary outcome was major adverse cardiac and cerebrovascular event (MACCE) at 3 years of follow-up. At 1 year of follow-up, the incidence of MACCE in group 1 was 10.1% of that in group 3, with a hazard ratio (HR) of 2.27, and 6.5% in group 2, with an HR of 1.415. This tendency continued up to 3 years of follow-up. The study demonstrated that lower incidence of MACCE in the high BMI group of Asians during the 3-year follow-up period compared to the low BMI group. The results implied higher BMI could exert a positive effect on the long-term clinical outcomes of patients with AMI undergoing percutaneous coronary intervention (PCI).

Dipeptidyl peptidase-4 inhibitors versus sulfonylureas on the top of metformin in patients with diabetes and acute myocardial infarction.

Background: Recent trials have shown that both the extent of glycated hemoglobin reduction and the duration of enhanced glycemic control are major factors that may affect cardiovascular outcome results. We aimed to investigate the impact of metformin (MET) combined with dipeptidyl peptidase-4 (DPP4) inhibitors or sulfonylureas (SU) on long-term clinical outcomes in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM). Methods: This study was a prospective cohort trial. From November 2011 to December 2015, a total of 13,104 AMI patients were consecutively enrolled from the Korea AMI registry-National Institutes of Health. The patients were divided into the MET + DPP4 inhibitors group and the MET + SU group. The primary endpoint, major adverse cardiac events (MACE), was defined as the composite of all-cause death, recurrent myocardial infarction (MI), and any repeat revascularization up to 3-year follow-up. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. Results: Baseline well-matched two groups were generated (the MET + DPP4 inhibitors group, n=468 and the MET + SU group, n=468). During 3-year clinical follow-up, the cumulative incidence of MACE between the two groups was not significantly different after adjustment (16.8% for MET + DPP4 inhibitors group vs. 19.4% for MET + SU group, P=0.302). However, the MET + DPP4 inhibitors group was associated with reduced risk of MI [1.3% vs. 4.9%; hazard ratio (HR): 0.228, 95% confidence interval (CI): 0.090-0.580, P=0.001] than the MET + SU group. Conclusions: In patients with AMI and type 2 DM, the use of MET combined with DPP4 inhibitors was associated with reduced incidence of recurrent MI than MET combined with SU during 3-year follow-up.

Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury.

INTRODUCTION: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). METHODS: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. RESULTS: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. CONCLUSION: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.