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This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR‐hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open‐label, single‐center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low‐, medium‐, and high‐dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half‐life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3‐day period. [ABSTRACT FROM AUTHOR]

Background: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock., Methods: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald χ (2) tests were used to compare the strength of relationships., Results: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all-cause mortality; these in the highest vs. lowest quartiles of SBP (≥140 vs. <110mm Hg) and PP (≥60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (χ (2) = 5.9 for per 10mm Hg, χ (2) = 10.8 for quartiles) or women (χ (2) = 15.1 for per 10mm Hg, χ (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years., Conclusions: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis., Methods: Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele)., Results: A total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%., Conclusions: Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.

Objective: To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction., Methods: From June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose., Results: The mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05)., Conclusion: Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

Objective: The aim of the present work was to investigate the potential relationship between acute rejection and serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP)/high sensitivity C reactive protein (hs-CRP) in post-transplant patients., Methods: Sixty-one consecutive orthotopic heart transplantation recipients were prospectively recruited from the cardiac transplantation programme at Fuwai Hospital. Endomyocardial biopsies (EMB) were performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB were also performed when patients had new symptoms of heart failure or at 2 weeks after steroid pulse therapy. Serum NT-proBNP and hs-CRP were simultaneously measured before EMB procedure., Results: A total of 126 biopsy samples were obtained from the 61 patients. Serum NT-proBNP concentrations progressively decreased after transplantation (spearman correlation coefficient -0.520, P = 0.000). NT-proBNP levels within 6 months after transplantation were significantly higher than those beyond 6 months post transplantation [(11.86 +/- 11.16) x 10(-16) mol/L vs.(5.83 +/- 6.58) x 10(-16) mol/L, P = 0.002]. NT-proBNP concentrations in patients with rejection tended to be higher than patients without rejection (13.68 x 10(-16) mol/L vs. 9.26 x 10(-16) mol/L, P = 0.073). After time adjustment, the difference of NT-proBNP concentrations between patients with or without rejection becomes statistically significant (14.45 x 10(-16) mol/L vs. 9.1 x 10(-16) mol/L, P = 0.025). Receiver operating characteristics analysis for NT-proBNP versus rejection grade revealed an area under the curve of 0.566, indicating a low predictive value for NT-proBNP. A cutoff of 6.00 x 10(-16) mol/L yielded poor specificity (44.8%) and sensitivity (57.1%), the sensitivity and specificity were 38.1% and 61.0%, respectively with a cutoff of 8.00 x 10(-16) mol/L. hs-CRP levels within 6 months after transplantation tended to be higher than those beyond 6 months [(2.39 +/- 3.90) mg/L vs. (1.34 +/- 2.73) mg/L, P = 0.069]. hs-CRP concentrations in patients with rejection were similar as patients without rejection (2.995 mg/L vs. 1.833 mg/L, P = 0.138). The incidence of rejection was similar in patients with two higher biomarkers (5/20, 25%) compared to patients with two low biomarkers (3/26, 11.5%, P = 0.232)., Conclusions: NT-proBNP level decreased after transplantation. Although increased NT-proBNP concentrations were related to rejection, the diagnostic capacity was low. Elevated hs-CRP concentrations were not related to rejection after heart transplantation.