Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study.

BACKGROUND: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD). OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial. METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years). RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group. CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).

Impact of guideline-directed medical therapy on 5-year mortality in patients with newly diagnosed peripheral artery disease.

OBJECTIVE: Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis. METHODS: This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality. RESULTS: We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P < .001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P < .001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately. CONCLUSIONS: After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Consensus Decision-Making for the Management of Antiplatelet Therapy before Non-Cardiac Surgery in Patients Who Underwent Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents: A Cohort Study.

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic-bleeding risks, it has been left to an individualized decision-making based on physicians' perspectives before non-cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug-eluting stents. Methods and Results A total of 3582 adult patients undergoing non-cardiac surgery after percutaneous coronary intervention with second-generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non-cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98-3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31-7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45-3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.

Patterns of Antiplatelet Therapy During Noncardiac Surgery in Patients With Second-Generation Drug-Eluting Stents.

Background Continuing antiplatelet therapy (APT) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second-generation drug-eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second-generation drug-eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all-cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P=0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69-1.44; P=0.995). In subgroup analysis, patients undergoing intra-abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI, 0.08-0.91; P=0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36-8.38; P=0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second-generation drug-eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra-abdominal surgery. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03908463.

Isoproterenol Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Embryonic Kidney Cells through Death Receptor 5 up-Regulation.

BACKGROUND AND OBJECTIVES: Chronic impairment of ß-adrenergic receptor signaling increases cardiac apoptosis, hypertrophy and fibrosis. The aim of this study was to investigate whether isoproterenol (ISO), an agonist of the adrenergic receptor, can enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human embryonic kidney (HEK) 293 cells. MATERIALS AND METHODS: HEK 293 cells were treated with ISO and/or TRAIL for 24 hours. Cell viability was evaluated by microscopy and an established viability assay, and apoptotic cell death was analyzed by staining with fluorescein isothiocynate-annexin-V/propidium iodide (PI) and caspase activation. To confirm the mechanism of cell death induced by co-treatment with ISO and TRAIL, expression of TRAIL receptor 2 (death receptor 5, DR5) was evaluated by immunoblotting. RESULTS: Although ISO or TRAIL treatment decreased HEK 293 cell viability by 13% and 17%, respectively, co-treatment with ISO and TRAIL resulted in a markedly higher death rate of 35% after 24 hours. Increases were evident in early apoptotic cells (i.e., annexin-V positive/PI negative; 19.4%), late apoptotic cells (i.e., annexin-V positive/PI positive; 6.3%) and dead cells (i.e., annexin-V negative/PI positive; 1.1%) when cells were co-treated with ISO and TRAIL, compared to cells treated with either ISO or TRAIL. In addition, marked increases of cleaved cas-3, cleaved poly (adenosine diphosphate-ribose) polymerase and DR5 were observed in HEK 293 cells co-treated with ISO and TRAIL. CONCLUSION: Treatments combining ISO with TRAIL may be responsible for death of HEK 293 cells through DR5 up-regulation. Activation of adrenergic receptors is responsible for the synergistic cell death observed with TRAIL.

Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction.

To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85

A pharmacodynamic study of the optimal P2Y12 inhibitor regimen for East Asian patients with acute coronary syndrome.

BACKGROUND/AIMS: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). METHODS: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU ≤ 275) and Caucasian (85 < PRU ≤ 208) criteria for assessing the therapeutic window of OPR. RESULTS: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). CONCLUSIONS: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.

Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

Myocarditis often occurs due to viral infections and postviral immune-mediated responses. Hypersensitivity myocarditis is a rare form of myocarditis. Numerous drugs can induce myocarditis, which is typically reversible after withdrawal of the causative agent. Here, we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug. A 68-year-old woman presented with acute chest pain mimicking acute coronary syndromes, but the coronary angiography was normal. A recent history of taking medications, skin rash, and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis, which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

A prospective study of epicardial adipose tissue and incident metabolic syndrome: the ARIRANG study.

Increased epicardial adipose tissue (EAT) may be closely associated with the development of metabolic abnormalities. We investigated whether EAT predicts the incident metabolic syndrome in a community-based, middle-aged population. The study subjects were comprised of 354 adults (134 men and 220 women) aged 40 to 70 yr without metabolic syndrome. Baseline EAT thickness, measured by echocardiography, was compared between subjects who developed new-onset metabolic syndrome at follow-up survey and those who did not. After an average of 2.2 yr of follow-up, 32 men (23.9%) and 37 women (16.8%) developed metabolic syndrome. Median EAT thickness at baseline was significantly higher in male subjects who developed metabolic syndrome than those who did not (1.52 mm vs 2.37 mm, P<0.001). The highest quartile of EAT thickness (≥2.55 mm) was associated with increased risk of progression to metabolic syndrome (Odds ratio [OR], 3.09; 95% confidence interval [CI], 1.11-8.66) after adjustment for age, smoking, alcohol intake, regular exercise, total energy intake, high sensitive C-reactive protein and homeostasis model assessment of insulin resistance in men. A significant association of EAT with incident metabolic syndrome was not seen in women (OR, 1.25; 95% CI, 0.54-2.90). In conclusion, increased EAT thickness is an independent predictor for incident metabolic syndrome in men.

Different prognostic significance of high on-treatment platelet reactivity as assessed by the VerifyNow P2Y12 assay after coronary stenting in patients with and without acute myocardial infarction.

OBJECTIVES: This study compared the prognostic role of high on-treatment platelet reactivity (HTPR) in predicting thrombotic events in a Korean population undergoing percutaneous coronary intervention (PCI) in the acute myocardial infarction (AMI) and non-AMI setting. BACKGROUND: The prognostic significance and optimal cutoff of HTPR might differ according to a given clinical condition, such as AMI and ethnicity. METHODS: On-treatment platelet reactivity was measured with a VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in 1,226 patients (824 men; age 65 ± 10 years), including 413 AMI cases, 12 to 24 h after PCI between March 2008 and March 2010. The prevalence of cardiovascular (CV) events defined as a composite of death from CV causes, nonfatal myocardial infarction, or stent thrombosis at 1-year follow-up were compared according to HTPR between patients with and without AMI. RESULTS: The optimal cutoff for HTPR was 272 IU of the P2Y(12) reaction unit (PRU) (area under the curve: 0.708; 95% confidence interval [CI]: 0.607 to 0.809, p = 0.03), which was the upper-tertile threshold. Among AMI patients, 1-year CV events occurred more frequently in patients with versus without HTPR (n = 14 [8.8%] vs. n = 1 [0.4%], p < 0.001), whereas there was no difference in the composite endpoint on the basis of HTPR in patients without AMI (n = 7 [2.8%] vs. n = 8 [1.4%], p = 0.193). CONCLUSIONS: Increased residual platelet reactivity is related to post-discharge CV events in subjects with AMI, whereas the prognostic significance of HTPR seems to be attenuated in patients with stable coronary disease after PCI.

Intravascular ultrasound-guided primary percutaneous coronary intervention with drug-eluting stent implantation in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Studies investigating the clinical outcome of intravascular ultrasound (IVUS)-guided primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) show conflicting results. The aim of our study was to evaluate whether IVUS-guidedPPCI with drug-eluting stents (DESs) in STEMI patients improves clinical outcome. HYPOTHESIS: IVUS-guided PPCI is superior to angio-guided PPCI. METHODS: Three hundred forty-one patients who underwent PPCI for STEMI and survived the hospitalization were enrolled in this study. Two hundred sixteen (63.3%) patients were treated with angio-guided PPCI and 125 (36.7%) patients were treated with IVUS-guided PPCI. The primary endpoint was defined as the composite of death, myocardial infarction, target vessel revascularization, and target lesion revascularization at the 3-year follow-up visit. RESULTS: Male gender, dyslipidemia, and smoking were frequent in the IVUS-guided PPCI group. These patients had a higher rate of radial approach, adjunctive ballooning, thrombectomy, and the use of a glycoprotein IIb/IIIa inhibitor. The number and length of implanted stents were higher in the IVUS-guided PPCI group. The primary end point (18.1% vs 12.8%, P = 0.22) and stent thrombosis (2.8% vs 2.4%, P = 1.00) was not different between the groups. CONCLUSIONS: In our observational study, IVUS-guided PPCI with DESs in patients with STEMI did not improve clinical outcome or stent thrombosis.

Urine Albumin Creatinine Ratio is Associated with Carotid Atherosclerosis in a Community Based Cohort: Atherosclerosis Risk of Rural Area in Korean General Population Study.

BACKGROUND: Albuminuria is a surrogate marker of endothelial dysfunction and a predictor of cardiovascular events. Data are limited with regard to the relationship between albuminuria and subclinical atherosclerosis in a community-based cohort. We determined the association between albuminuria measured by the urine albumin creatinine ratio (UACR) and carotid intima media thickness (CIMT) in a Korean rural population. METHODS: We enrolled 1,369 healthy subjects older than 40 years (857 males and 518 females) with normal renal function and measured the CIMT. We excluded subjects with overt proteinuria (> 300 mg/day) or with treatment of diabetes mellitus, hypertension, dyslipidemia, and any cardiovascular disease. The subjects were stratified into the quartile value of the UACR (lowest quartile: UACR < 4.8 and highest quartile: UACR > 17.7). And we evaluate the relationship between UACR and CIMT by linear regression and logistic regression analysis. RESULTS: Increasing quartile of the UACR had a stepwise increase in body mass index, blood pressure, cholesterol profile [low density lipoprotein (LDL)-cholesterol and triglyceride], glucose, homeostratic model assessment of insulin resistance (HOMA-IR), and C-reactive protein (all p values < 0.001). Maximal CIMT from the 1(st) to the 4(th) quartile values of the UACR were 0.74 ± 0.17, 0.77 ± 0.18, 0.78 ± 0.18, and 0.82 ± 0.21 mm, respectively (p < 0.001). In a multivariate regression model adjusted for age, sex, systolic blood pressure, triglyceride, LDL-cholesterol, fasting blood sugar, waist circumference, adiponectin, HOMA-IR, high sensitive C-reactive protein, smoking, UACR showed a significant association with maximal CIMT (B = 0.014, R(2) = 0.145, p = 0.002). CONCLUSION: Albuminuria measured by the UACR was significantly associated with both CIMT and traditional risk factors of atherosclerosis except for smoking in healthy Koreans.