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Background No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agents users. Methods Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. The Cox proportional hazards model was used to compare mortality outcomes among the PS-matched cohort as the primary analysis. The Cox proportional hazards models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as the secondary analyses. Results Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0.50, 95% confidence interval [CI] 0.26–0.95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0.30, 95% CI 0.17–0.54 while adjusting for all pre-determined covariates, and aHR 0.34, 95% CI 0.19–0.59 while adjusting for quintiles of the PS). Conclusions Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. However, a detrimental effect of any of the comparators could not be excluded.

BACKGROUND: Ischemia-reperfusion injury following acute ST-segment elevation myocardial infarction (STEMI) is strongly related to inflammation. However, whether intracoronary (IC) tacrolimus, an immunosuppressant, can improve myocardial perfusion is uncertain. METHODS: A multicenter double-blind randomized controlled trial was conducted in Taiwan from 2014 to 2017. Among 316 STEMI patients with Killip class ≤ 3 undergoing primary percutaneous coronary intervention (PCI), 151 were assigned to the study group treated with IC tacrolimus 2.5 mg to the culprit vessel before first balloon inflation, and the remaining 165 were assigned to the placebo group receiving IC saline only. The primary endpoint was percentage of post-PCI TIMI-3 flow. The primary composite endpoints included achievement of TIMI-3 flow, TIMI- myocardial perfusion (TMP) grade, or 90-min ST-segment resolution (STR). The secondary endpoints were left ventricular ejection fraction (LVEF) and 1-month/1-year major adverse cardio-cerebral vascular events (MACCEs) (defined as death, myocardial infarction, stroke, target-vessel revascularization or re-hospitalization for heart failure). RESULTS: Although post-PCI TIMI-3 epicardial flow and MACCE rate at 1 month and 1 year did not differ between the two groups, TMP grade (2.54 vs. 2.23, p < 0.001) and 90-min STR (67% vs. 61%, p < 0.001) were significantly higher in the tacrolimus-treated group than in the placebo group. The STEMI patients treated with tacrolimus also had significantly higher 3D LVEF and less grade 2 or 3 LV diastolic dysfunction at 9 months compared to those without. CONCLUSIONS: IC tacrolimus for STEMI improved coronary microcirculation and 9-month LV systolic and diastolic functions. However, the benefit of tacrolimus on clinical outcomes remains inconclusive due to insufficient patient enrollment.

Background: No randomized controlled trials evaluating metformin therapy efficacy in patients with type 2 diabetes mellitus (DM) and acute coronary syndrome (ACS) have been reported. Well-designed retrospective studies controlling for imbalance in baseline patient characteristics are scarce. We aimed to examine the mortality benefit of metformin therapy in patients with type 2 DM and ACS, compared with non-metformin anti-diabetes agent users. Method: Data were extracted from the prospective nationwide ACS-DM Taiwan Society of Cardiology registry. Propensity score (PS) matching on baseline characteristics and treatment measures was performed for metformin versus non-metformin users. Cox proportional hazard models were used to compare mortality outcomes among the PS-matched cohort as a primary analysis. Traditional Cox proportional hazard models adjusting for all pre-determined covariates and quintiles of the PS among the overall population were performed as a secondary analysis. Findings: Of 1157 patients with type 2 DM and ACS receiving anti-diabetes agents, 78 patients (6.7%) died over the 2-year follow-up period. After PS matching, 318 metformin users were matched with 318 non-metformin users. Metformin users had a lower all-cause mortality rate (adjusted hazard ratio [aHR] 0·50, 95% confidence interval [CI] 0·26-0·95) in the primary analysis. The survival benefit of metformin therapy was consistent in the secondary analyses (aHR 0·30, 95% CI 0·17-0·54 while adjusting for all pre-determined covariates, and aHR 0·34, 95% CI 0·19-0·59 while adjusting for quintiles of the PS). Interpretation: Among patients with type 2 DM and ACS, metformin was associated with lower all-cause mortality. Funding Statement: This work was supported with grants from the Hsin-Chu branch of the National Taiwan University Hospital (HCH-106036). The funding source also provided technical help (Biotechnology R&D Center) with data analysis and interpretation of the findings. Declaration of Interest: All authors report no relationships that could be construed as a conflict of interest. Ethics Approval Statement: Patients are treated according to international or local guidelines and evidence-based strategies. The protocol and consent forms used in this study were consistent with the Declaration of Helsinki and relevant regulations. The ethics committees of each participating hospital approved the study, and all enrolled patients provided written informed consent.

We tested whether intracoronary (IC) administration of tacrolimus could improve myocardial perfusion and clinical outcomes following primary percutaneous intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). A multicenter double-blind randomized-controlled trial (

Background: Slow-flow and no-reflow phenomenon which occurred frequently during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) caused unfavorable prognostic outcomes. Currently, no effectively therapeutic strategy to prevent this phenomenon. Objectives/Design: To evaluate the efficacy and safety of intra-Coronary Administration of Tacrolimus prior to firstballoon inflation, a pilot study was performed. Methods/Results of Pilot Study: Twenty-nine STEMI patients (group 1) were first prospectively administered tacrolimus (2.5 mg intra-coronary slow injection using thrombuster) prior to first-balloon inflation. A historical-control group (group 2) was chosen from fifty-two consecutive patients undergoing primary PCI just prior to the pilot study. Age, gender, CAD-risk factors, peak CK-BM, and baseline left-ventricular performance were not different between groups 1 and 2 (all p>0.1). Chest pain onset-to-door and door-to-balloon times, mean Killip score upon presentation, number of multi-vessel disease, pre-PCI TIMI flow, and 30-day death were similar between these two groups (all p>0.1). The incidences of advanced CHF (≥ NYHA 3) and pulmonary edema were higher in group 2 than in group 1, whereas the incidence of anterior-wall infarction, final TIMI-3 flow and 90 minute ST-segment-resolution rate showed an opposite pattern of advanced CHF between these two groups. The incidence of myocardial blushing grade was significantly higher in group 2 than in group 1 (p=0.034). Conclusion: Tacrolimus therapy shows promise as a safe and effective therapeutic agent for STEMI. The positive preliminary outcomes from this pilot study suggests randomized-controlled trials are now required to evaluate the effectiveness and safety of Tacrolimus for STEMI patients. (clinical trials no: ISRCTN38455499).

The aim of this study was to assess the reproducibility and diagnostic performance for coronary artery disease (CAD) of an automated software package, 4D-MSPECT, and compare the results with a visual approach. We enrolled 60 patients without previously known CAD, who underwent dual-isotope rest Tl-201/stress Tc-99m sestamibi myocardial perfusion imaging and subsequent coronary angiography within 3 months. The automated summed stress score (A-SSS), summed rest score (A-SRS) and summed difference score (A-SDS) were obtained using a 17-segment five-point scale model with 4D-MSPECT. For intraobserver and interobserver variability assessment, automated scoring was done by a nuclear medicine physician twice and by a nuclear medicine technologist. The visual summed stress score (V-SSS), summed rest score (V-SRS), and summed difference score (V-SDS) were obtained by consensus of two nuclear medicine physicians. The intraobserver and interobserver agreements of automated segmental scores were excellent. The intraobserver and interobserver summed scores also correlated well. Agreements between visual and automated segmental scores were moderate (weighted kappa of 0.55 and 0.50 for stress and rest images, respectively). Correlations between automated and visual summed scores were high, with correlation coefficients of 0.89, 0.85 and 0.82 for SSS, SRS and SDS, respectively (all p0.001). The receiver operating characteristic area under the curve for diagnosis of CAD by V-SSS, V-SDS, A-SSS and A-SDS were 0.78 +/- 0.06, 0.87 +/- 0.05, 0.84 +/- 0.05 and 0.90 +/- 0.04, respectively. A-SDS had better diagnostic performance than A-SSS and V-SSS (p = 0.043 and p = 0.032, respectively), whereas there was no statistically significant difference between A-SDS and V-SDS (p = 0.56). Using V-SDSor = 2 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 83.7%, 76.5% and 81.7%, respectively. Using A-SDSor = 3 as a diagnostic threshold, the sensitivity, specificity, and accuracy for CAD were 79.1%, 82.4% and 80.0%, respectively. In conclusion, the reproducibility of automated semiquantitative analysis with 4D-MSPECT was excellent. The diagnostic performance of automated semiquantitative analysis with 4D-MSPECT was comparable with the visual approach.