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Abstract Backgrounds High-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI. Method Data was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM). Results A total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02). Conclusion In patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI. Graphical abstract Cumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention.

Background The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long‐term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction. Methods and Results A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long‐term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%–49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow‐up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group (P65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high‐risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high‐risk mrEF group was comparable with the rEF group, while it was lower in the low‐risk mrEF group than in the pEF group. Conclusions Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high‐risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.

Background Little is known about the characteristics and long‐term clinical outcomes of patients with heart failure with improved ejection fraction (HFimpEF) after acute myocardial infarction. Methods and Results From a multicenter, consecutive cohort of patients with acute myocardial infarction undergoing percutaneous coronary intervention, patients with an initial echocardiogram with left ventricular ejection fraction ≤40% and at least 1 follow‐up echocardiogram after 14 days and within 2 years of the initial event were considered for analyses. HFimpEF was defined as an initial left ventricular ejection fraction ≤40% and serial left ventricular ejection fraction >40% with an increase of ≥10% from baseline at follow‐up. Independent factors predicting HFimpEF were identified, and clinical outcomes of patients with HFimpEF were compared with those without improvement. From an initial cohort of 10 719 patients with acute myocardial infarction, 191 patients with HFimpEF and 256 patients with non‐HFimpEF who had initial and follow‐up echocardiographic data were analyzed. The median follow‐up duration was 4.5 (interquartile range, 2.9–5.0) years. The factors predicting HFimpEF were lower peak creatine kinase myocardial band, smaller left ventricular dimensions, lower ratio between early mitral inflow velocity and mitral annular early diastolic velocity ′, and the use of β blockers or renin–angiotensin system blockers at discharge. HFimpEF was associated with a significantly decreased risk of all‐cause death compared with non‐HFimpEF (hazard ratio, 0.377 [95% CI, 0.234–0.609]; P

Abstract Background Potent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS. Methods The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting). Results A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56–2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups. Conclusions Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI. Trial registration: KCT0002356, registered June 13, 2017.

BackgroundThe use of a cardioverter defibrillator for the primary prevention of sudden cardiac death is not recommended within 40 days after acute myocardial infarction (AMI). We investigated the predictors for early cardiac death among patients who were admitted for AMI and successfully discharged.MethodsConsecutive patients with AMI were enrolled in a multicenter prospective registry. Among 10,719 patients with AMI, 554 patients with in-hospital death and 62 patients with early non-cardiac death were excluded. Early cardiac death was defined as a cardiac death within 90 days after index AMI.ResultsEarly cardiac death after discharge occurred in 168/10,103 (1.7%) patients. A defibrillator was not implanted in all patients with early cardiac death. Killip class ≥3, chronic kidney disease stage ≥4, severe anemia, cardiopulmonary support usage, no dual antiplatelet therapy at discharge, and left ventricular ejection fraction (LVEF) ≤35% were independent predictors for early cardiac death. The incidence of early cardiac death according to the number of factors added to LVEF criteria in each patient was 3.03% for 0 factor, 8.11% for 1 factor, and 9.16% for ≥2 factors. Each model that sequentially added the factors in the presence of LVEF criteria showed a significant gradual increase in predictive accuracy and an improvement in reclassification capability. A model with all factors showed C-index 0.742 [95% CI 0.702–0.781], p < 0.001; IDI 0.024 [95% CI 0.015–0.033], p < 0.001; and NRI 0.644 [95% CI 0.492–0.795], p < 0.001.ConclusionWe identified six predictors for early cardiac death after discharge from AMI. These predictors would help to discriminate high-risk patients over current LVEF criteria and to provide an individualized therapeutic approach in the subacute stage of AMI.

Abstract Background Intensive glycemic control is generally recommended for diabetic patients to reduce complications. However, the role of glycemic control in the mortality in diabetic patients with acute myocardial infarction (AMI) remained unclear. Methods We selected diabetic patients who measured HbA1c more than 3 times after AMI among 10,719 patients enrolled in the multicenter AMI registry. Patients (n = 1384) were categorized into five groups: according to mean HbA1c level: ≤ 6.5%, > 6.5 to ≤ 7.0%, > 7.0 to ≤ 7.5%, > 7.5 to ≤ 8.0% and > 8.0%. The primary endpoint was all-cause mortality. Results During a median follow-up of 6.2 years, the patients with a mean HbA1c of 6.5 to 7.0% had the lowest all-cause mortality. Compared to patients with mean HbA1c of 6.5 to 7.0%, the risk of all-cause mortality increased in subjects with mean HbA1c ≤ 6.5% (adjusted hazard ratio [HR] 2.00, 95% confidence interval [CI] 1.02–3.95) and in those with mean HbA1c > 8.0% (adjusted HR 3.35, 95% CI 1.78–6.29). In the subgroup analysis by age, the J-curve relationship between mean HbA1c and all-cause mortality was accentuated in elderly patients (age ≥ 65 years), while there was no difference in all-cause mortality across the HbA1c groups in younger patients (age

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all‐cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50–4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30–29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69–57.07]). The risk of all‐cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04–8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81–9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

Background Real‐world data on low baseline low‐density lipoprotein cholesterol (LDL‐C) levels and long‐term postdischarge cardiovascular outcomes in patients with acute coronary syndrome are limited. Methods and Results Of the 10 719 patients enrolled in the Korean registry of acute myocardial infarction between January 2004 and August 2014, we identified 5532 patients who were event free from death, recurrent myocardial infarction, or stroke during the in‐hospital period after successful percutaneous coronary intervention. The co–primary outcomes were 3‐point major adverse cardiovascular events (a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and cardiovascular death at 5 years. Of 5532 patients with acute myocardial infarction (mean age, 62.1±12.8 years; 75.0% men), 446 cardiovascular deaths (8.1%) and 695 three‐point major adverse cardiovascular events (12.6%) occurred at 5 years. In the continuous analysis of LDL‐C, the risk of cardiovascular events increased steeply as LDL‐C levels decreased from 100 mg/dL. For categorical analysis of LDL‐C (

Background The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI). Methods Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger (Results In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 [5.4%] vs. 329 [6.8%], adjusted hazard ratio [aHR] 0.76; 95% confidence interval [CI] 0.59–0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 [11.4%] vs. 131 [10.6%], aHR 1.1; 95% CI 0.76–1.59; P = 0.63). Conclusions In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.

Cutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underlying mechanisms remain unclear. Determining the vascular endothelial growth factor (VEGF) contents in a human vascular smooth muscle cell (VSMC)-conditioned medium was assessed using human VEGF immunoassay and vascular reactivity using porcine coronary artery rings. Later, C57BL/6 or db/db mice were anesthetized, after which a 6-mm biopsy punch was manipulated for perforation via the back skin. Subsequently, CAPE was applied to the wound and changed daily. Furthermore, the injury in each mouse was digitally photographed, and the wound area was quantified. We observed that CAPE increased VEGF levels in human VSMC-conditioned medium, improved endothelium-dependent nitric oxide (NO)-mediated vasorelaxation, inhibited U46619-induced vasoconstriction porcine coronary artery, and enhanced cutaneous wound healing in the diabetic mouse model. Hence, we propose that CAPE improves wound healing in diabetic mice, which is aided by increased VEGF and NO expression.

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The benefit of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) for noninfarctrelated artery (IRA) lesions with angiographically severe stenosis in patients with acute myocardial infarction is unclear. METHODS: Among 562 patients from the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infraction Related Artery Stenosis in Patients With Acute Myocardial Infarction) who were randomly allocated into either FFR-guided or angiography-guided PCI for non-IRA lesions, the current study evaluated the relationship between non-IRA stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI. The incidence of the primary end point (death, myocardial infarction, or repeat revascularization) was compared between FFRand angiography-guided PCI according to non-IRA stenosis severity (QCA stenosis ≥70% or <70%). RESULTS: A total of 562 patients were assigned to FFR-guided (n=284) versus angiography-guided PCI (n=278). At a median follow-up of 3.5 years, the primary end point occurred in 14 of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patients with QCA stenosis ≥70% (8.5% versus 19.2%; hazard ratio, 0.41 [95% CI, 0.22–0.80]; P=0.008), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiographyguided PCI among those with QCA stenosis <70% (3.9% versus 11.1%; P=0.315). There was no significant interaction between treatment strategy and non-IRA stenosis severity (P for interaction=0.636). FFR-guided PCI was associated with the reduction of death and myocardial infarction in both patients with QCA stenosis ≥70% (6.7% versus 15.1%; P=0.008) and those with QCA stenosis <70% (1.0% versus 9.6%; P=0.042) compared with angiography-guided PCI. CONCLUSIONS: In patients with acute myocardial infarction and multivessel disease, FFR-guided PCI tended to have a lower risk of primary end point than angiography-guided PCI regardless of non-IRA stenosis severity without significant interaction. [ABSTRACT FROM AUTHOR]

BackgroundWe evaluated the effectiveness of extended dual antiplatelet therapy (DAPT) usage after 2nd-generation drug elution stent implantation in acute myocardial infarction (AMI) survivors with high ischemic risk characteristics who had no major bleeding for 24 months under at least 1 year of DAPT maintenance.Materials and methodsThe primary ischemic and bleeding endpoints were the risk of mortality and the risk of BARC 3 or 5 (major) bleeding. We investigated the event rates for 2–5 years after the index procedure.ResultsOf 3382 post-AMI survivors who met the PEGASUS-TIMI 54 (PEGASUS) criteria and without major bleeding until 2 years, 2281 (67.4%) maintained DAPT over 24 months, and 1101 (32.5%) switched DAPT to a single antiplatelet agent. The >24 M DAPT group showed a lower risk of mortality than the 12–24 M DAPT group (7.2 vs. 9.2%; adjusted hazard ratio: 0.648; 95% confidence interval: 0.595–0.976; p < 0.001). The mortality risk was significantly greater as the number of PEGASUS criteria increased (p < 0.001). DAPT > 24 months was not significantly associated with a decreased risk for major bleeding in the population meeting the PEGASUS criteria (2.0 vs. 1.1%; p = 0.093). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences.ConclusionExtended DAPT over 24 months was associated with a lower risk of mortality without increasing the risk of major bleeding among 2 years survivors after AMI who met the PEGASUS criteria and had no major bleeding events before 24 months.