OBJECTIVETo evaluate the efficacy and safety of tirofiban use immediately after successful percutaneous coronary intervention (PCI) in patients with moderate to high risk non-ST segment elevation acute coronary syndromes (NSTE-ACS).

METHODSNSTE-ACS patients undergoing successful PCI (n = 246) were randomized by the envelope method to tirofiban group (n = 122, 10 µg/kg bolus within 3 min followed by 0.10-0.15 µg×kg(-1)×min(-1) for 36 h i.v.) or control group (n = 124, saline i.v. for 36 h). The primary efficacy composite end point was death, myocardial infarction, target vascular revascularization or ischemic stroke at 30 days. The second end point was the occurrence of composite end point at 7 days or 6 months. Key safety end points were bleeding and thrombocytopenia 3 days after PCI.

RESULTSBaseline characteristics were well-balanced between the two groups (P > 0.05). The primary end point occurred in 0.9% (1/117) patients in the tirofiban group and 3.3% (4/123) patients of those in the control group (P = 0.40). There was no significant difference in the composite end point at 7 days [0.8% (1/122) vs. 3.2% (4/124), P = 0.38] between the groups, however, there was a trend towards lower composite efficacy end points at 6 months in tirofiban group compared to control group [0.9% (1/117) vs. 5.9% (7/118), P = 0.07]. The probability of survival free of composite end point was significantly higher in the tirofiban group than that in the control group (99.2% vs. 94.2%, log-rank test, P = 0.03). There was no GUSTO severe or moderate bleeding or severe thrombocytopenia within 3 days post-PCI. There was no significant difference in mild bleeding [13.1% (16/122) vs. 7.3% (9/124), P = 0.13] or mild thrombocytopenia [0.8% (1/122) vs. 0.8% (1/124), P = 1.00] between the groups.

CONCLUSIONTirofiban use after successful PCI can improve 6-month event-free survival without increasing the risk of bleeding for patients with moderate to high risk NSTE-ACS.

Acute Coronary Syndrome ; therapy ; Aged ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Prognosis ; Treatment Outcome ; Tyrosine ; administration & dosage ; analogs & derivatives ; therapeutic use

OBJECTIVETo investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM).

METHODSWeight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip.) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.

RESULTSMortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01).

CONCLUSIONAng(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.

Angiotensin I ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Cardiomyopathy, Dilated ; chemically induced ; pathology ; physiopathology ; Caspase 3 ; metabolism ; Doxorubicin ; adverse effects ; Heart ; drug effects ; Male ; Myocytes, Cardiac ; drug effects ; pathology ; Peptide Fragments ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Ventricular Dysfunction, Left ; drug therapy ; bcl-2-Associated X Protein ; metabolism ; bcl-X Protein ; metabolism

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator