糖尿病心血管并发症的药物防治

糖尿病已被列为冠心病的等危因素，美国心脏协会甚至提出了“糖尿病是一种心血管疾病”的观点。大部分糖尿病患者在确诊前已有多年隐匿的病史，开始治疗时往往已存在不同程度的心血管并发症。在同年龄组内，糖尿病患者冠心病的发病率和死亡率比非糖尿病人群高3～6倍，曾发生心肌梗死的糖尿病患者的7年死亡率更高达42％，糖尿病患者心血管疾病的患病率及预后均远差于非糖尿病人群。     

2型糖尿病心血管并发症的药物干预

2型糖尿病心血管并发症是造成患者高致残率、高致死率的主要原因。目前相关的防治药物重点针对2型糖尿病的心血管危险因素,主要包括降糖药、调血脂药、肾素-血管紧张素系统药物等,活血祛瘀中药在国内亦有较多应用。本文将对这些药物的临床研究进行综述。     

严格控制血压，降低糖尿病心血管事件

唐尿病慢性并发症尤其是血管并发症是影响糖尿病患者生命质量与寿命的主要原因。糖尿病是多种代谢异常的聚集体，在2型糖尿病中，血脂异常、血压异常、胰岛素抵抗、氧化应激异常、凝血机制异常及嘌呤代谢异常的发生率很高，所有这些代谢异常均参与了2型糖尿病并发症的发生发展，并且各自有不同的“贡献”。有关糖尿病患者血压的研究表明，糖尿病患者高血压的患病率在30％～60％。     

高血压人群心血管事件的发生情况及影响因素的问卷调查

目的：了解高血压人群中心血管事件（包括死亡、脑出血、脑梗死、心肌梗死和心绞痛）的发生情况及其影响因素。方法：把心血管事件作为因变量,对影响因素进行非条件logistic回归分析。结果：发病时间长、服药依从性差、有家族史、吸烟、嗜酒、四药以上联合、心脑血管病、糖尿病是社区高血压人群不良心血管事件发生的危险因素,其中服药依从性差、糖尿病、吸烟、心脑血管病是主要不良心血管事件发生的独立危险因素;二药联合、非药物治疗是不良心血管事件发生的独立保护因素。     

NT-proBNP水平对糖尿病合并冠心病患者心血管事件和预后的影响

目的：探讨NT-proBNP水平对糖尿病合并冠心病患者心血管事件和预后的影响。方法选取本院2012年3月~2014年3月收治的202例2型糖尿病合并冠心病患者作为研究对象,依据NT-proBNP水平将入选患者分为NT-proBNP≤86 ng/L组和NT-proBNP>86 ng/L组,各101例。采用多因素Logistic回归分析筛选出与急性心血管事件相关的影响因素,并比较两组的差异。结果多因素Logistic回归分析显示,心血管事件的发生与NT-proBNP水平密切相关（P<0.01）。 NT-proBNP>86 ng/L组的心血管事件发生率显著高于NT-proBNP≤86 ng/L组,差异有统计学意义（P<0.01）。NT-proBNP>86 ng/L组的空腹血糖、总胆固醇、低密度脂蛋白、载脂蛋白B水平及冠状动脉完全闭塞发生率显著高于NT-proBNP≤86 ng/L组,差异有统计学意义（P<0.05）。结论 NT-proBNP水平与糖尿病合并冠心病患者心血管事件及心血管事件发生的危险因素密切相关。     

抗高血压药物研发进展

高血压是多种心血管事件的主要诱发因素之一,针对高血压的治疗最直接且最有效的方式为通过各种手段综合降低血压。针对高血压药物的研发与进展,世界各国对于高血压药物的研发主要集中于直接抗高血压药物的研究。单独应用抗高血压药物虽然可以发挥有效的降压作用,但是抗高血压药物的耐药性及顽固性高血压的治疗仍是抗高血压治疗的重点研发领域。目前针对抗高血压药物治疗瓶颈的解决方式主要分为寻找新靶点药物和固定剂量联合用药,但仍有巨大的临床缺口需要更加深入的基础研究,为抗高血压药物的研发提供新的靶点。     

2型糖尿病患者下肢血管粥样硬化斑块超声表现与作为阻塞性冠状动脉疾病和心血管事件预测因子的临床价值

目的 分析2型糖尿病(T2DM)患者下肢血管粥样硬化斑块的超声表现与作为阻塞性冠状动脉疾病及心血管事件预测因子的临床价值。方法 90例T2DM伴冠状动脉粥样硬化性心脏病(CHD)患者设为CHD组,结合冠状动脉造影结果分为单支组、双支组、三支组,各30例;另选取同期90例健康体检者设为对照组。比较四组基线资料;观察下肢动脉超声分级结果 ;比较四组下肢血管内-中膜厚度(IMT)及下肢动脉超声分级结果 ;分析T2DM伴CHD患者心血管事件发生的影响因素。结果 四组的肌酸激酶、肌酸激酶同工酶、甘油三酯水平比较,差异具有统计学意义(P<0.05)。三支组的肌酸激酶、肌酸激酶同工酶、甘油三酯水平高于双支组、单支组、对照组,双支组高于单支组、对照组,单支组高于对照组,差异具有统计学意义(P<0.05)。CHD组下肢血管超声显示无粥样硬化19例, 27例存在下肢动脉硬化, 19例下肢动脉狭窄<50%/斑块、25例下肢动脉狭窄≥50%/闭塞。四组下肢IMT及下肢动脉超声分级比较,差异具有统计学意义(P<0.05)。三支组的下肢IMT(1.64±0.45)mm大于双支组的(1.30...     

罗格列酮对2型糖尿病合并冠心病患者心血管事件的影响

目的 分析罗格列酮治疗2型糖尿病合并冠心病患者的心血管事件影响.方法 选取我科住院89例2型糖尿病合并冠心病患者,按照治疗方案不同分为:对照组,47例,常规治疗,研究组,42例,在常规治疗结合罗格列酮治疗.随访1年后,比较两组患者的心梗、接受血运重建术、2级以上心衰、卒中以及猝死等心血管事件的发生率.结果 研究组患者的心梗、接受血运重建术、卒中以及猝死发生率较对照组减少,但无统计学差别(P＞0.05);研究组患者的2级以上心衰发生率明显增加(P＜0.05).结论 罗格列酮治疗2型糖尿病合并冠心病患者对缺血性心血管事件无明显影响,但可以增加充血性心力衰竭风险.     

新型抗糖尿病药物FFA1受体激动剂的研究进展

尽管目前建立的治疗Ⅱ型糖尿病的治疗方案取得了一定成效,但是仍然没有满足人类对新型的更加安全有效的抗糖尿病药物的需求.在这个领域FFA1受体已成为近年来一个很有吸引力的靶标.FFA1受体不仅通过刺激胰岛β细胞促使胰岛素分泌,同时能作用于场内分泌细胞促使肠促胰岛素分泌.最新的研究进展和临床数据表明,FFA1受体激动剂是治疗Ⅱ型糖尿病的潜力药物.     

心血管系统药物的合理应用

摘要：药物联用治疗是心血管疾病的主要治疗手段,临床上如何合理应用心血管疾病药物是临床医生重点关注的问题。本文结合近年来临床试验的结果和文献资料,对心血管疾病常用药物在患者中的治疗作用和不良反应以及由病人个体差异原因造成的不同后果等方面进行循证研究。     

某院2016年-2018年间抗糖尿病药物临床使用相关因素分析

目的:分析医院2016年—2018年间抗糖尿病药物使用的相关因素,为临床合理用药提供参考。方法:抽取2016年1月—2018年12月间抗糖尿病药物的使用数据,采用Excel 2007版统计软件,分析其抗糖尿病药物的销售金额、构成比、用药频度、日均药品费用。结果:医院2016年—2018年间抗糖尿病药物销售金额逐年增长,且除胰岛素类药物之外,其他降糖药物所占比例超过60%;二甲双胍片、阿卡波糖片、西格列汀片的销售总金额、用药频度居前3位,属于糖尿病患者常用药物。结论:3年间抗糖尿病药物使用情况较为合理,双胍类、α-糖苷酶抑制剂及DDP-4抑制剂类药物市场份额占比较大,可为临床糖尿病患者用药提供了治疗手段。     

TLC法筛查中药制剂中的14种化学降糖药物

目的:筛查中药制剂中非法添加的14种化学降糖药物。方法:建立薄层色谱法,采用硅胶GF254薄层板,分别以氯仿-甲醇-甲酸(12∶8∶0.03)和氯仿-环己烷-甲醇-冰醋酸(8∶8∶0.5∶1.5)为展开剂进行筛查。结果:26批样品中有8批添加了化学降糖药物。结论:本法简便有效,不需特殊仪器,可用于降糖类中药制剂的质量监控。     

HPLC法测定中成药中9种化学降糖药的研究

目的：建立测定添加在降糖中成药中的格列吡嗪、格列本脲、格列齐特、格列喹酮、格列美脲、盐酸吡格列酮、盐酸罗格列酮、那格列奈、瑞格列奈共9种化学降糖药的高效液相分析方法。方法：色谱柱：ThermoC18（150mm×4．6mm,5μm）,流动相：醋酸盐缓冲溶液（10mmol·L-1醋酸铵和20mmol·L-1三乙胺,醋酸调pH至5．5）-乙腈（61：39）,流速：1ml·min-1,检测波长：210nm,柱温：30℃,进样20山。结果：9种化学降糖药完全分离,检出限为4～18ng;9种药物具有宽的线性范围和良好的线性关系（r≥0．9994）;日内、日问RSD分别为O．09％～1．42％和O．30％～1．88％;在中药中的加样回收率除个别药物低浓度外均大于80％,RSD为0．26％-5．91％。结论：该方法用于检测中成药中的化学降糖药快速、简便、高效。     

166份抗糖尿病药品说明书中妊娠妇女用药信息标注情况调查分析

目的:为规范抗糖尿病药品说明书中妊娠妇女用药信息标注提供参考。方法:收集丁香园用药助手中收录的所有抗糖尿病药品说明书,分析其中妊娠妇女用药信息标注情况。结果:166份药品说明书中,147份(88.55%)有单独列出"孕妇及哺乳期妇女用药"项,并对妊娠妇女用药信息进行了标注;14份(8.43%)也有列出该项,但仅标注尚无临床资料或临床资料有限,未提示妊娠妇女可否用药;5份(3.01%)无"孕妇及哺乳期妇女用药"项。在无用药指导意见中,指导意见缺失3份(1.81%),临床资料无/有限14份(8.43%);在有用药指导意见中,指导意见为禁用49份(29.52%),不得/不宜/不应使用40份(24.1%),慎用/不推荐/权衡利弊/益处大于风险时使用/向医师咨询49份(29.52%),可用/使用不受限制11份(6.63%)。166份药品说明书中,26份为国外药企药品说明书,均有单独列出"孕妇及哺乳期妇女用药"项,且有妊娠妇女用药指导意见。结论:国内药品说明书标注内容存在妊娠妇女用药相关信息缺失、指导意见表述不统一、更新滞后等问题,应引起药品监督管理部门、药品生产企业的重视。     

Inpatient Costs of Major Cardiovascular Events

Objective

Many trials of new therapies for cardiovascular disease include economic measures to assess the impact of treatment on healthcare costs, however, it is difficult to compare results between trials due to variation in methods for assigning costs. Therefore we developed a standard library of inpatient hospital costs for major cardiovascular events commonly reported in trials for new cardiovascular therapies.

Design

Mean and median hospital charges for each event were calculated from Medicare admissions selected by ICD-9-CM codes from the most recent Healthcare Cost and Utilisation Project (HCUP) Nationwide Inpatient Sample (NIS) database available. Charges were converted to costs using the cost-to-charge ratio from the most recent Medicare cost report data and updated to 1999 using a model derived from the Medicare Payment Advisory Commission (MedPAC) forecast to recommend annual updates to Medicare.

Results

Total hospital costs for medical events ranged from $US3654 (1999 values) to $US7833; total hospital costs for surgery and procedures ranged from $US7054 to $US46 317. The distribution of hospital costs is skewed with median costs and lengths of stay lower than mean values. Costs for patients who died in the hospital were generally higher than costs for patients who were discharged.

Conclusions

The library of costs was calculated using a uniform method based on publicly available and easily accessible data and may be updated from year to year. This method provides standardised estimates of hospital costs that can be used in economic analyses of cardiovascular clinical trials.     

Interactions Between Grapefruit Juice and Cardiovascular Drugs

Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.     

Risk of Suicide in Users of Cardiovascular Drugs

An association between consumption of cardiovascular drugs and increased risk of depression was first reported more than 30 years ago. More recently three observational studies have also reported an association between the use of cardiovascular drugs and risk of suicide. We review the epidemiological evidence with particular focus on bias, confounding, and chance as alternative explanations to a causal association. The results of the three studies are inconsistent with respect to the association between cardiovascular drug use and suicide. None of the studies has been able to control fully for possible confounding, in particular by the underlying disease and comorbidity. We thus conclude that the finding of an association between suicide risk and cardiovascular drug use remains dubious. A true explanation for the apparent increase in risk of suicide in users of cardiovascular drugs remains unknown. Future studies must try to reduce confounding. Meta-analyses of data from existing trials may be an approach to solve the problem of confounding.