The efficacy and safety of ivabradine hydrochloride versus atenolol in Chinese patients with chronic stable angina pectoris.

PURPOSE: The aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris. METHODS: In this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5 mg bis in die (BID)] or Aten group (12.5 or 25 mg BID) according to computer-generated random numbers for 12 weeks. RESULTS: One hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3 ± 120.1 seconds with Iva 5 mg and 58.8 ± 114.7 seconds with Aten 12.5 mg at the fourth week, and at the 12th week, TED improved by 84.1 ± 130.5 seconds with Iva and 77.8 ± 126.6 seconds with Aten (95%CI: -21.4-34.1 seconds, p = 0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0 seconds, p = 0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p > 0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p = 0.0035). CONCLUSIONS: Iva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe.

Development and validation of a liquid chromatography-tandem mass spectrometric assay for pitavastatin and its lactone in human plasma and urine.

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with electrospray ionization (ESI) was developed and validated for the simultaneous determination of pitavastatin and its lactone in human plasma and urine. Following a liquid-liquid extraction, both the analytes and internal standard racemic i-prolact were separated on a BDS Hypersil C(8) column, using methanol-0.2% acetic acid in water (70: 30, v/v) as the mobile phase. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode using the transition m/z 422.4-->m/z 290.3 for pitavastatin, m/z 404.3-->m/z 290.3 for pitavastatin lactone and m/z 406.3-->m/z 318.3 for the internal standard, respectively. Linear calibration curves of pitavastatin and its lactone were obtained in the concentration range of 1-200 ng/ml, with a lower limit of quantitation of 1 ng/ml. The intra- and inter-day precision values were less than 4.2%, and accuracies were between -8.1 and 3.5% for both analytes. The proposed method was utilized to support clinical pharmacokinetic studies of pitavastatin in healthy subjects following oral administration.

Clinical Characteristics and Risk Factors of Left Ventricular Thrombus after Acute Myocardial Infarction: A Matched Case-control Study.

BACKGROUND: Left ventricular thrombus (LVT) is reported to be a common complication in acute myocardial infarction (AMI) patients. And it has the potential to cause systemic embolism. This retrospective study was to present the current situation of LVT in clinical practice, as well as to evaluate the clinical characteristics and the risk factors of LVT after AMI. METHODS: LVT cases (n = 96) were identified from 13,732 AMI (non-ST elevation myocardial infarction was excluded) patients in Fuwai Hospital's electronic medical records system from January 2003 to January 2013. The controls (n = 192) were gender- and age-matched AMI patients without LVT during this period. A conditional logistic regression (fitted by the Cox model) was performed to identify the independent risk factors. RESULTS: The incidence of LVT after AMI was 0.7%. Univariate analysis indicated that the anterior myocardial infarction (especially extensive anterior myocardial infarction), lower left ventricular ejection fraction (LVEF), LVEF ≤40%, severe regional wall motion abnormalities (RWMA), pericardial effusion, and left ventricular aneurysm were all related to LVT after AMI. The independent risk factors obtained from the conditional logistic regression analysis were lower LVEF (odds ratio (OR) = 0.891, 95% confidence interval (CI ): 0.828-0.960), extensive anterior myocardial infarction (OR = 6.403, 95% CI: 1.769-23.169), severe RWMA (OR = 7.348, 95% CI: 1.323-40.819), and left ventricular aneurysm (OR = 6.955, 95% CI: 1.673-28.921). CONCLUSIONS: This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice.

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease.

BACKGROUND: Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients. METHODS: Overall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis. RESULTS: Compared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (ß = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I. CONCLUSIONS: This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

2-Methoxyestradiol and 2-ethoxyestradiol retard the progression of renal disease in aged, obese, diabetic ZSF1 rats.

The metabolic syndrome is a main cause for cardiovascular disease and for the accelerating epidemic of chronic renal failure. Previous studies show that 2-hydroxyestradiol (2-HE), an estradiol metabolite with little estrogenic activity, decreases obesity and arterial blood pressure and attenuates the development of renal disease in young, obese, diabetic ZSF1 rats. In humans, however, diabetic renal disease is more frequent and severe in older patients. In vivo, 2-HE is readily converted to 2-methoxyestradiol (2-ME), an estradiol metabolite with no estrogenic activity. Accordingly, one purpose of this study was to determine whether 2-ME would provide benefit in aged rats with a very severe form of diabetic renal disease. Another objective was to determine whether synthetic analogs of estradiol metabolites might be beneficial in diabetic renal disease. To achieve these objectives we examined the effects of 2-ME and its analog 2-ethoxyestradiol (2-EE) in aged (35-week-old), obese ZSF1 rats. Animals were treated for 9 weeks with vehicle (PEG-400, 0.5 microL per hour), 2-ME or 2-EE (18 microg/kg per hour). Metabolic and renal function were measured at weeks 0, 3, 6, and 9, and renal hemodynamics and excretory function were assessed at week 9. Aged ZSF1 rats had elevated levels of glycosylated hemoglobin; increased renal cortical expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NF-kappaB), and vascular endothelial growth factor (VEGF); glycosuria, hypertension; and proteinuria. 2-ME and 2-EE did not affect obesity or hypertension and had variable effects on glucose homeostasis, yet they attenuated proteinuria; increased renal blood flow and glomerular filtration; and reduced renal cortical expression of PCNA, NFkappaB, and VEGF. We conclude that 2ME and 2EE are strikingly renoprotective even in aged animals with severe diabetic renal disease. The present study warrants further investigation of 2-ME and analogs of estradiol metabolites for treatment of kidney disease associated with the metabolic syndrome.