Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial.

BACKGROUND: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. METHODS: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. RESULTS: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. CONCLUSIONS: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.

Predicting long-term bleeding after percutaneous coronary intervention.

OBJECTIVES: To construct a model to predict long-term bleeding events following percutaneous coronary intervention (PCI). BACKGROUND: Treatment with dual antiplatelet therapy following PCI involves balancing the benefits of preventing ischemic events with the risks of bleeding. There are no models to predict long-term bleeding events after PCI. METHODS: We analyzed 1-year bleeding outcomes from 3,128 PCI procedures in the Patient Risk Information Services Manager (PRISM) observational study. Patient-reported bleeding events were categorized according to Bleeding Academic Research Consortium (BARC) definitions. Logistic regression analysis was used to develop a model predicting BARC ≥ 1 bleeding. RESULTS: BARC 0, 1, 2 or 3 bleeding was observed in 574 (18.4%); 2382 (76.2%); 114 (3.6%); and 58 (1.8%) patients, respectively. Compared to patients who had no bleeding, patients with BARC ≥ 1 bleeding were more often female (30 vs. 23%), Caucasian (94 vs. 83%), had a higher incidence of drug eluting stent (DES) implantation (83 vs. 76%) and warfarin therapy (7.4 vs. 3.9%), and a lower incidence of diabetes (31 vs. 45%; P-value <0.01 for all comparisons). A 27-variable model had moderate discrimination (c-statistic of 0.674), and good calibration, as did a parsimonious model with 10 variables (c-statistic = 0.667). This model performed well in predicting BARC ≥ 2 bleeding events as well (c-statistic = 0.653). CONCLUSIONS: Bleeding is common in the first year after PCI, and can be predicted by pre-procedural patient characteristics and use of DES. Objective estimates of bleeding risk may help support shared decision-making with respect to stent selection and duration of antiplatelet therapy following PCI. © 2016 Wiley Periodicals, Inc.

Initial Total Bilirubin and Clinical Outcome in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Drug-Eluting Stents.

BACKGROUND: Total bilirubin (TB) concentration is inversely associated with stable coronary artery disease, but there have been few studies on initial TB in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 1,111 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DES) were divided into a high TB group (n=295) and a low TB group (n=816) according to the optimal cut-off 0.79 mg/dl. The high TB group had a higher rate of in-hospital major adverse cardiac events (MACE), a composite of cardiac death, non-fatal MI, and definite/probable stent thrombosis (14.2% vs. 4.2%, P<0.001) and cardiac death (13.9% vs. 3.9%, P<0.001) compared with the low TB group. The 30-day MACE-free survival rate was also significantly different between the groups (P<0.001, log-rank test). On multivariate Cox regression, initial high TB was a significant predictor of in-hospital MACE (HR, 2.69; 95% CI: 1.67-4.34, P=0.010) and of cardiac death (HR 2.72, 95% CI: 1.67-4.44, P=0.012). Adding initial TB to TIMI risk score significantly improved prediction for in-hospital MACE according to net reclassification improvement (NRI=5.2%, P=0.040) and integrated discrimination improvement (IDI=0.027, P=0.006). CONCLUSIONS: Initial TB is a powerful prognostic marker, and inclusion of this can improve prediction of in-hospital MACE in patients with STEMI undergoing primary PCI with DES. (Circ J 2016; 80: 1437-1444).

Comparison of new adenosine diphosphate receptor antagonists with clopidogrel in patients with coronary artery disease: a meta-analysis.

Recent data suggest the superiority of new adenosine diphosphate (ADP) receptor antagonists compared with clopidogrel in acute coronary syndrome patients. We aimed to assess the risks and benefits of new ADP receptor antagonists in patients with coronary artery disease (CAD). Relevant studies published through February 28, 2014 were searched and identified in the MEDLINE, EMBASE, and Cochrane databases. Summary estimates were obtained using a random-effects model. All nine published randomized controlled studies comparing new ADP receptor antagonists with clopidogrel in CAD were included. The database consisted of 66,900 patients; 33,782 on novel agents, and 33,118 on clopidogrel. New ADP receptor antagonists reduced the composite incidence of all-cause mortality, myocardial infarction or stroke (odds ratio [OR] 0.89, 95 % confidence interval [CI] 0.81-0.97, p = 0.01) but increased the incidence of non-coronary artery bypass grafting-related major bleeding (OR 1.24, 95 % CI 1.08-1.42, p = 0.003). The composite end point of the net rate of adverse clinical events, which was the combination of the primary efficacy end point and the primary safety end point, was significantly lower in the new agent group compared to the clopidogrel group (9.7 versus 10.6 %, OR 0.92, 95 % CI 0.85-1.00). Use of recently introduced new ADP receptor antagonists results in a reduction in adverse clinical outcomes but a substantial increase in bleeding. New agents revealed an improved combined efficacy and safety outcome compared to that of clopidogrel in patients with CAD.

Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial.

BACKGROUND: The risks and benefits of long-term dual antiplatelet therapy remain unclear. METHODS AND RESULTS: This prospective, multicenter, open-label, randomized comparison trial was conducted in 24 clinical centers in Korea. In total, 5045 patients who received drug-eluting stents and were free of major adverse cardiovascular events and major bleeding for at least 12 months after stent placement were enrolled between July 2007 and July 2011. Patients were randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin (n=2531). The primary end point was a composite of death resulting from cardiac causes, myocardial infarction, or stroke 24 months after randomization. At 24 months, the primary end point occurred in 57 aspirin-alone group patients (2.4%) and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence interval, 0.66-1.35; P=0.75). The 2 groups did not differ significantly in terms of the individual risks of death resulting from any cause, myocardial infarction, stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%) of the aspirin-alone group and dual-therapy group patients, respectively (hazard ratio, 0.71; 95% confidence interval, 0.42-1.20; P=0.20). CONCLUSIONS: Among patients who were on 12-month dual antiplatelet therapy without complications, an additional 24 months of dual antiplatelet therapy versus aspirin alone did not reduce the risk of the composite end point of death from cardiac causes, myocardial infarction, or stroke. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186146.

AWAJI criteria are not always superior to the previous criteria: A meta-analysis.

INTRODUCTION: Recently, some authors have claimed that the Awaji criteria (AC) are not always more sensitive than the revised El Escorial criteria (rEEC) in amyotrophic lateral sclerosis (ALS). METHODS: A meta-analysis examined 2 prospective and 7 retrospective studies, which included 1,121 ALS patients, to compare AC and rEEC for early diagnosis of ALS. RESULTS: AC led to an 11% greater likelihood of being classified into the categories "clinically definite" or "clinically probable", while if confined to the "clinically probable - laboratory supported (LS)" category, this effect was 40% higher with the rEEC (95% cnfidence interval, 3-82%; I2=98%). Specifically, AC downgraded 20% of the rEEC "clinically probable - LS" category to the AC "clinically possible". CONCLUSIONS: Despite overall superiority of AC, this meta-analysis shows that it is not always more sensitive than rEEC. These results are related to the requirement for 2 upper motor neuron signs in the AC "clinically probable" category.

Preventive versus culprit-only percutaneous coronary intervention in ST-elevation myocardial infarction patients with multivessel disease: a meta-analysis.

BACKGROUND: Although previous studies have suggested clinical benefits of complete revascularization in patients with multivessel coronary artery disease, it is still controversial whether preventive percutaneous coronary intervention (PCI) leads to better clinical outcomes in the clinical setting of ST-segment elevation myocardial infarction (STEMI). METHODS: Relevant studies through September 2014 were searched and identified in the electronic databases.Primary endpoint was all-cause mortality at the longest follow-up. Secondary endpoints included myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). RESULTS: From 836 initial citations, 7 randomized trials, and 23 observational studies with 44,256 patients (8,087 preventive and 36,169 culprit-only) were included in this study. Preventive PCI was associated with a significant reduction in repeat revascularization (odds ratios [OR]: 0.71; 95% CI: 0.51­0.99) with no differences in all-cause mortality (OR: 0.99; 95% CI: 0.76­1.29) or MI (OR: 1.08; 95% CI: 0.62­1.87) as compared with culprit-only PCI.Comparison of preventive PCI to the culprit-only PCI group revealed OR for MACE of 0.80 (95% CI: 0.57­1.12).Stratified analysis according to revascularization strategy demonstrated a significant survival benefit of culprit-only PCI over multivessel PCI during the index procedure and a significantly lower incidence of all-cause mortality with staged PCI as compared with culprit-only or multivessel PCI during the index procedure. CONCLUSIONS: Preventive PCI strategy appears to be effective in reducing the risk of repeat revascularization without significant benefits for mortality or MI when compared with culprit-only revascularization in STEMI patients with multivessel disease.

Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease.

Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p's < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization.

Left atrial myxoma presenting as paroxysmal supraventricular tachycardia.

Cardiac myxomas are benign intracavitary neoplasms. Their incidence in cardiac surgery is approximately 0.3%. Symptoms of cardiac myxomas are typically variable, from obstruction of mitral valve to coronary embolism resulting in acute myocardial infarction. In this case, left atrial myxoma is presented as paroxysmal supraventricular tachycardia.

Duration of dual antiplatelet therapy after implantation of drug-eluting stents.

BACKGROUND: The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. METHODS: In two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. RESULTS: The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06). CONCLUSIONS: The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)

Relation between the vasodilator-stimulated phosphoprotein phosphorylation assay and light transmittance aggregometry in East Asian patients after high-dose clopidogrel loading.

OBJECTIVES: We analyzed the relation between platelet aggregation measured by light transmittance aggregometry (LTA) and platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. BACKGROUND: It has been suggested that LTA and VASP-P assay correlate differently according to the level of P2Y12 receptor blockade by thienopyridines. METHODS: We simultaneously measured platelet function by LTA and VASP-P assay in 466 East Asians undergoing elective percutaneous coronary intervention after a 600-mg clopidogrel loading. High on-clopidogrel platelet reactivity (HPR) was defined by published consensus criteria. RESULTS: The degree of correlation between LTA and the VASP-P assay was different according to PRI levels. The correlation was lower in patients with poor responsiveness (PRI >60%) (n = 216) (0.035 ≤ r(2) ≤ 0.047), which was greater in responsive patients (PRI ≤60%) (n = 250) (0.315 ≤ r(2) ≤ 0.526). Despite a 600-mg loading, East Asians had a high prevalence of HPR (40.1%-63.5%), and the prevalence of HPR also differed between LTA and VASP-P assay. A PRI cutoff of >58% (area under curve, 0.829; 95% confidence intervals, 0.792-0.862; P < .001) corresponded to the published HPR cutoff by 5-µM adenosine diphosphate-induced maximal platelet aggregation >46%. CONCLUSIONS: This is the largest study correlating platelet reactivity measured by LTA and VASP-P assay in a percutaneous coronary intervention-treated cohort. The correlation is dependent on the level of responsiveness. Future investigations are needed to better define the optimal cutoffs of HPR measured by LTA and VASP-P assay for personalized antiplatelet therapy.

Prognostic value of creatine kinase-myocardial band isoenzyme elevation following percutaneous coronary intervention: a meta-analysis.

OBJECTIVES: To assess whether different degrees of creatine kinase-myocardial band isoenzyme (CK-MB) elevation after percutaneous coronary intervention (PCI) affect the subsequent risk of death. BACKGROUND: While there is consensus that extensive cardiac enzyme elevation increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations after PCI. METHODS: The published literature was scanned by formal searches of electronic databases such as PubMed and MEDLINE from January 1999 to October 2011. Risk ratio (RR) was used as summary estimate. RESULTS: Ten studies have been included totaling 48,022 patients who underwent PCI (12,246 patients with CK-MB elevation and 35,776 patients without CK-MB elevation). Mean followup duration for each study ranged from 6 to 48 months. CK-MB elevation >1× the upper limit of normal (ULN) conferred a significant increase in the risk of mortality with an overall RR of 1.74 (95% confidence interval [CI], 1.42 to 2.13, P < 0.001). Compared with patients without CK-MB elevation, there was a dose-response relationship with RR for death being 1.48 (95% CI, 1.25-1.77, P < 0.001) with CK-MB elevation 1 to <3× ULN, 1.71 (95% CI, 1.23-2.37, P = 0.001) with CK-MB elevation 3 to 5× ULN, and 2.83 (95% CI, 1.98-4.04, P < 0.001) with CK-MB elevation ≥ 5× ULN. CONCLUSIONS: Even a small increase in CK-MB levels after PCI is associated with significantly higher risk of late mortality. Monitoring cardiac enzymes after PCI may help predict the long term clinical outcome.

Randomized comparison of everolimus-eluting stent versus sirolimus-eluting stent implantation for de novo coronary artery disease in patients with diabetes mellitus (ESSENCE-DIABETES): results from the ESSENCE-DIABETES trial.

BACKGROUND: Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus. METHODS AND RESULTS: This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23 ± 0.27 versus 0.37 ± 0.52 mm; difference, -0.13 mm; 95% confidence interval, -0.25 to -0.02; upper 1-sided 95% confidence interval, -0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11 ± 0.26 versus 0.20 ± 0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups. CONCLUSION: Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.

Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury ­ a systematic review and meta-analysis ­.

BACKGROUND: Sodium bicarbonate has been postulated to prevent contrast-induced acute kidney injury (CI-AKI) by various mechanisms, although the reports are conflicting. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and the Cochrane databases for randomized controlled trials that compared a sodium chloride with a sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19 clinical trials consisting of 3,609 patients were combined. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36-0.86; P=0.008). Stratified analyses by the type of contrast medium suggested lower odds of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR 0.40; 95% CI 0.23-0.71, P=0.002) compared with those using the iso-osmolar agents (OR 0.76; 95% CI 0.41-1.43; P=0.40). No significant difference in the rates of postprocedural death (OR 0.49; 95% CI 0.23-1.04; P=0.06) and the requirement for renal replacement therapy (OR 0.94; 95% CI 0.46-1.91; P=0.86) was observed. However, we found significant changes in serum bicarbonate and potassium levels after sodium bicarbonate infusion. CONCLUSIONS: This updated meta-analysis demonstrates that sodium bicarbonate-based hydration is superior to sodium chloride in preventing CI-AKI of patients undergoing exposure to iodinated contrast media.

A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation.

OBJECTIVES: To evaluate the impact of cilostazol on the angiographic and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) with stents and treated with aspirin and thienopyridine. METHODS: A total of 11 randomized controlled trials including 8,525 patients comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included in the analysis. The primary end points were in-segment late loss and angiographic restenosis at angiographic follow-up. Secondary end points included mortality, stent thrombosis, target lesion revascularization (TLR) and major adverse cardiac events (MACE). RESULTS: Triple antiplatelet therapy was associated with a significant reduction in late loss [weighted mean difference 0.14, 95% confidence interval (CI) 0.08-0.20; p < 0.001] and angiographic restenosis [odds ratio (OR) 0.58, 95% CI 0.48-0.71; p < 0.001]. Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.56, 95% CI 0.41-0.77; p < 0.001) and MACE (OR 0.72, 95% CI 0.60-0.86; p < 0.001) with no differences in mortality (p = 0.29), stent thrombosis (p = 0.60) or bleeding episodes (p = 0.77). CONCLUSIONS: Cilostazol in addition to dual antiplatelet therapy appears to be effective in reducing the risk of restenosis and repeat revascularization after PCI without any significant benefits for mortality or stent thrombosis.

Negative regulation of adipogenesis by kaempferol, a component of Rhizoma Polygonati falcatum in 3T3-L1 cells.

Rhizoma Polygonati falcatum (RPF) has been used as a traditional herbal medicine in Asia, because of its anti-hyperglycemic, anti-triglycemic, and anti-tumor activity. In this study, we determined the anti-adipogenic potential of RPF extract and its component kaempferol in 3T3-L1 adipocytes, and the underlying molecular mechanism(s) using microarray analysis. Adipocyte differentiation of 3T3-L1 cells was significantly impaired by RPF extract and kaempferol as monitored by Oil Red O staining and quantitative measurement of lipid accumulation. Additionally, the mRNA expression of adipogenesis genes decreased on treatment with kaempferol. The role of kaempferol at the genome-wide level was further assessed by a microarray approach. Our analysis indicated that kaempferol decreased the expression of adipogenic transcription factors (Pparγ, Cebpß, Srebp1, Rxrß, Lxrß, Rorα) and genes involved in triglyceride biosynthesis (Gpd1, Agpat2, Dgat2), while increasing lipolysis-related genes, such as Tnfα, Lsr, and Cel. Finally, co-transfection assays using luciferase reporter gene and reverse transcription-polymerase chain reaction (RT-PCR) analysis using peroxisome proliferator-activated receptor-γ (PPARγ) target genes indicated that kaempferol significantly repressed rosiglitazone-induced PPARγ transcriptional activity. Overall, our data suggests that kaempferol, a major component of RPF, may be beneficial in obesity, by reducing adipogenesis and balancing lipid homeostasis partly through the down-regulation of PPARγ.

Cardiovascular outcomes with glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: According to available research, there have been no head-to-head studies comparing the effect of glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors on cardiovascular outcomes among patients with type 2 diabetes not reaching glycemic goal with metformin. METHODS: Relevant studies were identified through electronic searches of PubMed and EMBASE published up to January 15, 2020. Efficacy outcomes of interest included the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, its individual components, all-cause death, and hospitalization for heart failure (HF). Safety outcomes included all suggested side effects of both agents previously reported. RESULTS: Eleven studies, including 94,727 patients were used for the analysis. The risk of composite end point was significantly lower in both groups compared to the control group (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.85-0.92, p < 0.001). The risk of hospitalization for HF was significantly lower in both groups but the magnitude of the effect was more pronounced in the SGLT-2 inhibitors group (HR 0.68, 95% CI 0.60-0.76, p < 0.001) than the GLP-1 agonists group (HR 0.92, 95% CI 0.84-0.99, p = 0.03). Patients treated with GLP-1 agonists discontinued trial medications more frequently compared to conventionally treated patients because of serious side effects. CONCLUSIONS: Both GLP-1 agonists and SGLT-2 inhibitors showed comparable cardiovascular outcomes in patients with type 2 diabetes. However, the SGLT-2 inhibitors were associated with more pronounced reduction of hospitalization for HF and lower risk of treatment discontinuation than GLP-1 agonists.

Comparison of Different Types of Drug-Eluting Stents for De Novo Long Coronary Artery Lesions.

Background: Outcomes of percutaneous coronary intervention for diffuse long lesions remain relatively unfavorable. Prior clinical trials investigated the relative efficacy and safety of different types of drug-eluting stents (DES) in long lesions. Objectives: This study sought to compare the relative performance of different types of DES for de novo long (≥25 mm) coronary artery lesions. Methods: Using a pooled analysis of individual data of 1,450 patients from 3 randomized clinical trials, we compared angiographic and clinical outcomes of 5 different types of DES: 224 patients with cobalt-chromium everolimus-eluting stents (EES), 255 with platinum-chromium EES, 250 with Resolute zotarolimus-eluting stents, 245 with biodegradable polymer biolimus-eluting stents, and 476 with first-generation sirolimus-eluting stents (SES). The primary endpoint was in-segment late lumen loss at 9 months. Results: The primary endpoint was not significantly different between 4 second-generation DES and 1 first-generation SES (0.17 ± 0.41 mm in cobalt-chromium EES; 0.11 ± 0.37 in platinum-chromium EES: 0.14 ± 0.38 in Resolute zotarolimus-eluting stents; 0.14 ± 0.38 in biodegradable polymer biolimus-eluting stents; or 0.10 ± 0.37 in SES, respectively, overall P = 0.38). Also, there were no significant between-group differences with respect to death, myocardial infarction, target-vessel revascularization, or stent thrombosis at 12 months. In the multiple treatment propensity-score analysis, the risk of angiographic and clinical outcomes was also similar among several types of DES. Conclusions: In this patient-level pooled analysis, several second-generation DES showed similar angiographic and clinical outcomes in patients with de novo long coronary lesions. (Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-III [LONG-DES-III]; NCT01078038; Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV [LONG-DES-IV]; NCT01186094; and Everolimus-eluting [PROMUS-ELEMENT] vs. Biolimus A9-Eluting [NOBORI] Stents for Long-Coronary Lesions [LONG-DES-V]; NCT01186120).

Efficacy and Safety of 3 Versus 6 Months of Dual-Antiplatelet Therapy in Patients Implanted With a Coroflex ISAR Stents: A Prospective, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES), especially recently developed polymer-free DESs, is unknown. This study examined the efficacy and safety of 3- versus 6-month DAPT in patients implanted with Coroflex ISAR polymer-free DESs. METHODS: Between May 2015 and August 2020, 488 patients who underwent Coroflex ISAR stent implantation were enrolled in the study and randomly assigned to the 3-month (n=244) or 6-month (n=244) DAPT group. RESULTS: At 1 year, the primary endpoint (composite of cardiovascular death, myocardial infarction, target vessel revascularization, and Bleeding Academic Research Consortium [BARC] type 2-5 bleeding) occurred in 9 (3.7%) patients in the 3-month DAPT group and in 7 (2.9%) patients in the 6-month DAPT group (hazard ratio 1.31; P=.60). There was no difference between the 3- and 6-month DAPT groups in either BARC type 2-5 bleeding (1.6% vs 0.8%; hazard ratio 2.00; P=.42) or any bleeding (2.9% vs 3.3%; hazard ratio 0.87; P=.80). CONCLUSION: Compared with 6 months of DAPT, 3 months of DAPT did not increase the risk of primary endpoint 1 year after Coroflex ISAR stent implantation, although it should be noted that the trial has limited power to see differences due to low event rate and low recruitment rate.

Clinical outcomes and the risk factors of coronary artery aneurysms that developed after drug-eluting stent implantation.

BACKGROUND: There is only limited data on coronary artery aneurysms (CAA) after drug-eluting stent (DES) implantation. METHODS AND RESULTS: Two hundred-fifty one patients who had 2 angiographic follow-ups at 8 months and 28-36 months, respectively, after the index procedure with DES from 2003 to 2007 were enrolled. A CAA was defined as a localized dilatation exceeding 1.5 times the diameter of the adjacent artery. The independent risk factors and major adverse cardiac events (MACE) were determined, including cardiac death, myocardial infarction (MI) and target-vessel revascularization (TVR), between the patients with CAA (n=35) and without them (n=216). On multivariate analysis, a lesion in an infarct-related artery (IRA) (odds ratio (OR): 6.1, P=0.001), a lesion in the left anterior descending artery (OR: 4.9, P=0.005), a lesion length >33 mm (OR: 3.9, P=0.022), and a lesion with chronic total occlusion (CTO) (OR: 3.4, P=0.044) were the independent risk factors for CAA. Follow-up duration was 1,046±516 days. Although most patients (71.4%) were asymptomatic, MACE was found in 10 patients (28.6%). No deaths occurred. MI with stent thrombosis occurred in 5 patients (14.3%) and TVR occurred in 10 patients (28.6%). CONCLUSIONS: The risk factors for the development of CAA after DES are a long lesion over 33 mm, a lesion in the left anterior descending artery, a lesion in an IRA, and CTO. Long-term follow-up and large clinical trials are warranted for patients with CAA.