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Additional file 1: Figure S1. Anti-inflammatory effects of dapagliflozin on immunohistochemistry analysis. A-C The expression of RAM11, RAGE and TNF-α in the myocardium was detected by immunostaining. Values are means ± SEM (n = 10 per group). Scale bar = 200 μm. ***p < 0.001 compared to Control group, ††p < 0.01, †††p < 0.001 compared to Diabetes group. Figure S2. Dapagliflozin significantly decreased inflammation markers in H9C2. A RT-PCR expression of TNF-α and IL-6. Comparisons of relative mRNA expression, normalized to expression of β-actin. B Western blot expression of pNF-kB, NF-kB, TNF-α and IL-6. Representative data showing protein expression, normalized to expression of GAPDH. Values are means ± SEM (n = 6). *p < 0.05, **p < 0.01, ***p < 0.001 compared to Control, †p < 0.05 compared to DMSO, §p < 0.05, §§p < 0.01 compared to HG. GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IL-6, interlukin-6; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; TNF-α, tumor necrosis factor-α. Figure S3. Schematic design of the study protocol. Animals were randomized to Control, Diabetes, Diabetes+Dapa groups. Diabetic condition was induced for animals in Diabetes and Diabetes+Dapa groups. Dapagliflozin (1mg/kg/day) treated depending on their group assignment, for 8 weeks. After follow up echocardiography, animals were subsequently sacrificed and tissue samples were collected for assessment of histological and molecular remodeling. Table S1. List of rabbit primers. Table S2. List of H9C2 primers.

Supplemental Material for Effects of Hypertension on Two-Year Outcomes According to Glycemic Status in Patients With Acute Myocardial Infarction Receiving Newer-Generation Drug-Eluting Stents by Yong Hoon Kim, MD, PhD, Ae-Young Her, MD, PhD, Myung Ho Jeong, MD, PhD, Byeong-Keuk Kim, MD, PhD, Sung-Jin Hong, MD, Sang-Ho Park, MD, PhD, Seunghwan Kim, MD, Byung Gyu Kim, MD, Chul-Min Ahn, MD, PhD, Jung-Sun Kim, MD, PhD, Young-Guk Ko, MD, PhD, Donghoon Choi, MD, PhD, Myeong-Ki Hong, MD, PhD, and Yangsoo Jang, MD, PhD in Angiology

Additional file 1. Supplementary Appendix.

OBJECTIVES This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients. BACKGROUND Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited. METHODS Using 6 randomized trials that compared short-term (≤6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients (≥65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding. RESULTS The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p = 0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction = 0.0384). In the subset of younger patients (

BACKGROUND There is general agreement that the optimal duration of dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents should be individualized. We hypothesized that the extent of coronary artery disease may affect the clinical outcomes of DAPT. METHODS AND RESULTS We pooled patient-level data from 5 large, randomized trials comparing short-term DAPT with prolonged therapy. From the data, we identified 5476 patients who received newer-generation drug-eluting stents. Net adverse clinical event (NACE) was defined as a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding. At 1 year, NACE had occurred in 171 patients (3.1%). Independent predictors of NACE were older age (>65 years), sex, presence of diabetes mellitus, left ventricular dysfunction (ejection fraction

ObjectivesThis study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).BackgroundPrevious randomized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events (MACEs) in patients with stable angina pectoris and acute coronary syndrome. However, no randomized studies have been carried out with STEMI patients in a primary PCI setting.MethodsA total 171 patients with STEMI were randomized to 80-mg atorvastatin (n = 86) or 10-mg atorvastatin (n = 85) arms for pre-treatment before PCI. All patients were prescribed clopidogrel (600 mg) before PCI. After PCI, both groups were treated with atorvastatin (10 mg). The primary end point was 30-day incidence of MACE including death, nonfatal MI, and target vessel revascularization. Secondary end points included corrected thrombolysis in myocardial infarction frame count, myocardial blush grade, and ST-segment resolution at 90 min after PCI.ResultsMACE occurred in 5 (5.8%) and 9 (10.6%) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms, respectively (p = 0.26). Corrected thrombolysis in myocardial infarction frame count was lower in the 80-mg atorvastatin arm (26.9 ± 12.3 vs. 34.1 ± 19.0, p = 0.01). Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm (2.2 ± 0.8 vs. 1.9 ± 0.8, p = 0.02 and 61.8 ± 26.2 vs. 50.6 ± 25.8%, p = 0.01).ConclusionsHigh-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI. High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion. (Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction [STATIN STEMI]; NCT00808717).

ObjectivesThe goal of this study was to evaluate shorter duration (3 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation.BackgroundThere have been few published reports of prospective randomized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation.MethodsWe randomly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type: 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n = 1,059) versus 12-month DAPT following the other DES implantation (standard therapy, n = 1,058). We hypothesized that the E-ZES+3-month DAPT would be noninferior to the standard therapy for the primary composite endpoint (cardiovascular death, myocardial infarction, stent thrombosis, target\vessel revascularization, or bleeding) at 1 year.ResultsThe primary endpoint occurred in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%) patients assigned to the standard therapy (difference: 0.0%; 95% confidence interval [CI]: −2.5 to 2.5; p = 0.84; p < 0.001 for noninferiority). The composite rates of any death, myocardial infarction, or stent thrombosis were 0.8% and 1.3%, respectively (difference: −0.5%; 95% CI: −1.5 to 0.5; p = 0.48). The rates of stent thrombosis were 0.2% and 0.3%, respectively (difference: −0.1%; 95% CI: −0.5 to 0.3; p = 0.65) without its further occurrence after cessation of clopidogrel in the E-ZES+3-month DAPT group. The rates of target vessel revascularization were 3.9% and 3.7%, respectively (difference: 0.2%; 95% CI: −2.3 to 2.6; p = 0.70).ConclusionsE-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [RESET]; NCT01145079)

ObjectivesWe performed this study to investigate the vascular response in early period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic CardioVascular, Minneapolis, Minnesota) implantation.BackgroundThe ZES has different characteristics, with biocompatible polymer and rapid drug-elution, compared with the first-generation drug-eluting stents (DES).MethodsThe ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is a prospective, single-center study evaluating vascular healing patterns with optical coherence tomography (OCT) at 3 months after stent implantation. A total of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and 3 months. Neointimal growth and malapposition were analyzed at each stent strut of cross-sectional OCT images with 0.5-mm intervals.ResultsThe incidence of malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively. However, late acquired malapposition was not detected at 3 months. Of 31 stents, 27 stents (87.1%) were covered completely with neointima, but the remaining 4 stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall mean percentage of covered stent struts was 99.9 ± 0.4%. This finding was consistent among groups with acute coronary syndrome and stable angina pectoris (99.9 ± 0.3% vs. 99.9 ± 0.4%, p = 0.92). Intracoronary thrombus was documented in 1 stent (3.2%) among 31 stents.ConclusionsMost of the stent struts were covered with neointima, and late acquired malapposition was not found at 3 months after ZES implantation. Therefore, the current study demonstrated that ZES might have a favorable in vivo vascular response at 3 months after stent implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical Coherence Tomography [ENDEAVOR OCT]; NCT00815139)