目的 系统评价氯沙坦对比其他血管紧张素受体拮抗剂(ARB)对高血压患者血尿酸水平的影响,为临床有降尿酸需求的高血压患者用药决策提供循证证据.方法 检索PubMed、Embase、Cochrane Library、中国知网(CNKI)、万方、维普等数据库,纳入符合标准的随机对照研究(RCT)及队列研究.评价纳入研究质量并根据设计的Excel表格提取数据,以加权均数差(WMD)为效应量,使用RevMan5.4版、Stata 15版软件进行Meta分析,GRADEpro GDT网站进行证据质量评价.结果 共纳入24篇文献,其中13项RCT,11项队列研究.结果 显示,氯沙坦对比其他ARB能有效降低血尿酸水平,优于替米沙坦(WMD=-81.54,95％CI:-108.71～-54.38),缬沙坦(WMD=-92.19,95％CI:-125.49～-58.89),坎地沙坦酯(WMD=-27.34,95％CI:-35.92～-18.76)及厄贝沙坦(WMD=-91.82,95％CI:-148.00～-35.64);与奥美沙坦和依普沙坦(WMD=-12.62,95％CI:-32.54～7.30)相比差异无统计学意义.结论 当前证据显示,在ARB类降压药中,氯沙坦具有显著降低血尿酸水平的优势,且这一优势与目标人群是否合并高尿酸血症、氯沙坦剂量和用药时长无明显相关.

Objective This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events. Methods Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events. Results Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.929.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65-1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91-1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53-1.23) between the clopidogrel- and ticagrelor-treated groups. Conclusion In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.

目的 对2015-2019年国家自然基金资助的动脉硬化相关项目进行分析,探讨当前该领域的研究热点,为后续开展动脉粥样硬化相关研究提供参考.方法 统计2015-2019年立项的动脉粥样硬化相关项目,对立项年度、类型、学科分布等情况进行分析,并应用CiteSpace软件进行关键词可视化分析,探究当前国家自然科学基金对于动脉粥样硬化领域的资助热点.结果 近5年动脉粥样硬化相关项目的 立项总数为662项,每年立项数目整体较为稳定.其中所属医学科学部有612项(92.4％)占比最高,立项呈现多学科协同现象.资助项目地区分布不均衡,立项集中于北京、上海、广东等地区.关键词共现结果显示,巨噬细胞、炎症、内皮细胞为出现频率前3名的关键词.关键词聚类结果显示内皮细胞、巨噬细胞、微RNA为前3名的研究类团.结论 国家自然科学基金是国家对于基础研究的重要支撑,研究者应把握研究热点,多学科协同,多技术联用,推动动脉粥样硬化研究的更深层次探索.

Background: The clinical benefits of cytochrome P450 (CYP) 2C19 genotype-guided antiplatelet therapy in Asians remain unclear. In this study, we aimed to investigate the clinical outcomes of pharmacogenomic antiplatelet therapy in Chinese patients.Methods: Patients with acute coronary syndrome planning to undergo percutaneous coronary intervention were eligible for this study and were randomly divided into a genotype-guided treatment (GT) group and routine treatment (RT) group, with a ratio of 2:1. Patients in the GT group underwent CYP2C19 genotyping (*2 and *3 alleles), and the results were considered in selecting P2Y12 receptor inhibitors. Patients in the RT group were treated with P2Y12 receptor inhibitors according to their clinical characteristics. The primary endpoint was a composite of major adverse cardiovascular or cerebrovascular events (MACCE). The secondary endpoint was significant bleeding events.Results: Finally, 301 patients were enrolled; 75.1% were men and the mean age was 59.7 ± 9.8 years. In total, 281 patients completed the follow-up procedure. The primary endpoint occurred in 16 patients, 6 patients in the GT group and 10 in the RT group. The GT group showed lower MACCE rates than the RT group (6/189 vs. 10/92, 3.2 vs. 10.9%, hazard ratio: 0.281, 95% confidence interval: 0.102–0.773, P = 0.009). There was no statistically difference in significant bleeding events between the GT and RT groups (4.2 vs. 3.3%, hazard ratio: 1.315, 95% confidence interval: 0.349–4.956, P = 0.685).Conclusion: Personalized antiplatelet therapy that is based on CYP2C19 genotypes could decrease MACCE within a 12-month period in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000034352.

目的:评估国产与进口氯吡格雷口服常释剂型的有效性和安全性及药物经济学差异,为“4+7”带量采购政策执行对患者治疗模式和医疗费用支出的影响提供数据支持.方法:提取首都医科大学附属北京安贞医院急性冠脉综合征患者药物治疗相关因素与临床结局的病例,研究患者登记数据库中使用氯吡格雷患者的基线及随访信息及医院药品费用数据,根据所用药物品种分为中标药组及原研药组进行统计分析.结果:原研药组MACCE的发生率与中标药组(4.91％ vs.5.07％,P=0.83)无显著性差异,全因死亡、心血管相关死亡、心肌梗死、卒中、血运重建及支架内血栓等各单独终点事件及主要出血事件发生率与中标药组无显著性差异(log-rank P=0.60).2019年4-9月氯吡格雷用量较政策实施前2018年同期使用金额下降874.4万元.结论:中标品种氯吡格雷与进口同类药物相比,在急性冠脉综合征患者经皮冠状动脉介入治疗后的疗效可靠,安全性好,具有较大价格优势.

Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel in patients undergoing percutaneous coronary intervention for acute coronary syndrome. However, the clinical impact of implementing CYP2C19 gene-guided pharmacotherapy is unclear, especially among the Chinese population. The purpose of this study was to evaluate P2Y12 receptor inhibitor selection and clinical outcomes upon implementation of CYP2C19 genotype-guided pharmacotherapy in current clinical practice.Methods: This was a single-center observational cohort study. Adult percutaneous coronary intervention patients who received CYP2C19 genetic testing (*2, *3, *17 alleles) were included. Ticagrelor was recommended for patients with a LOF allele. Factors related to P2Y12 inhibitor selection were determined by logistic regression. The primary endpoint was major cardiac or cerebrovascular adverse events (MACCE) within 12 months. MACCE and clinically significant bleeding events (BARC ≥2) in the LOF-clopidogrel group, non-LOF-clopidogrel group, and non-LOF-ticagrelor group were compared with those in the LOF-ticagrelor group. The inverse probability of treatment weighting (IPTW) was adjusted in a Cox regression analysis to eliminate confounding factors.Results: Among 1,361 patients, 826 (60.7%) had a LOF allele. Patients with a LOF allele were more likely to be prescribed ticagrelor (multivariate-adjusted OR 1.349; 95% CI 1.040 to 1.751; p = 0.024). The MACCE rate was higher in the LOF-clopidogrel group than in the LOF-ticagrelor group (7.8 vs. 4.0%; log-rank p = 0.029; IPTW-adjusted HR 2.138; 95% CI 1.300–3.515). Compared with the LOF-ticagrelor group, the non-LOF-clopidogrel group showed no significant difference in MACCE rate (5.8 vs. 4.0%; log-rank p = 0.272; IPTW-adjusted HR 1.531; 95% CI 0.864–2.714). Among the patients treated with ticagrelor, there was no significant difference in the MACCE rate between the LOF group and non-LOF group (4.3 vs. 4.0%; log-rank p = 0.846; IPTW-adjusted HR 1.184; 95% CI 0.582–2.410). There was no significant difference in the incidence of clinically significant bleeding events among the four groups.Conclusion: This study confirms that efficiently returned CYP2C19 genotype results did partially guide cardiologists to prescribe ticagrelor for patients with a LOF allele, and that clopidogrel had a higher risk of MACCE than ticagrelor in these patients, which provides support for the implementation of CYP2C19 gene-guided antiplatelet therapy in clinical practice.

目的 系统评价复方利血平氨苯蝶啶片(北京降压0号)治疗原发性高血压的有效性和安全性.方法 检索PubMed、Cochrane、Web of Science、中国学术期刊全文数据库(CNKI)、维普数据库、万方数据库及百度学术数据库,中文检索词为复方利血平氨苯蝶啶片、降压零号、北京降压0号、高血压,英文检索词为com-pound reserpine and triamterene tablets、hypertension,筛选2000—2020年发表的研究复方利血平氨苯蝶啶片的安全性及有效性的随机对照试验.由2位研究员按纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Revman5.4软件进行Meta分析.结果 最终纳入7项研究.Meta分析结果显示:在5项研究中,与其他降压药相比,复方利血平氨苯蝶啶片降压总有效率更高(OR=2.23,95％CI:1.32～3.75);不良反应发生率差异无统计学意义(OR=0.91,95％CI:0.68～1.22).结论 复方利血平氨苯蝶啶片治疗原发性高血压较其他降压药物降压效果与安全性均更可靠.

目的 评价洛匹那韦/利托那韦抗新型冠状病毒治疗的应用可行性、临床效果及安全性.方法 最近在中国暴发的新型冠状病毒肺炎(简称新冠肺炎)疫情,目前尚无针对性强的抗病毒药物,临床尝试"老药新用",以2003年严重急性呼吸综合征(SARS)和2012年中东呼吸综合征(MERS)疫情中使用的一线抗病毒药物洛匹那韦/利托那韦来抗新型冠状病毒治疗.分析该药的抗病毒药理作用、临床应用可行性,评价其临床应用效果和安全性.结果 洛匹那韦/利托那韦治疗冠状病毒感染性疾病有一定临床基础,可重建宿主的免疫功能,抗新型冠状病毒有一定疗效,但有较高的耐药屏障.结论 洛匹那韦/利托那韦用于抗新型冠状病毒治疗可行,临床疗效较好,但应用期间要加强药学监护,尤其是合并用药和特殊人群应用时,注重安全、合理用药.