Clinical trials of an antiplatelet agent,ticlopidine, in diabetes mellitus

Summary

At present there is no simple, reliable and noninvasive method for monitoring progression and improvement in diabetic microangiopathy. However; some diabetic patients with severe microvascular complications show a fairly specific pattern of impaired left ventricular function (abnormal relaxation, cavity filling and wall thinning) and abnormalities of haemorheology (increased viscosity, erythrocyte rigidity and beta-thromboglobulin and decreased threshold for platelet ADP aggregation). A single-blind, 6-months’ crossover study of an antiplatelet agent, ticlopidine, was conducted in 20 diabetics with clinical evidence of microvascular disease. Response to therapy was monitored by digitised M-mode echocardio-graphic analysis of left ventricular diastolic function and haemorheology. All patients had abnormal basal values with no significant change during the 3-month placebo run-in period but, although significant alterations in viscosity, erythrocyte deformability, beta-thromboglobulins and ADP threshold were observed, no change in left ventricular function was detected. It is concluded that, while it may be possible to alter abnormal haemorheology in diabetes, there was no change in one parameter of microvascular end-organ damage.     

三七总皂苷联合双重抗血小板药物治疗对冠状动脉支架术后患者心血管事件的影响

目的 研究三七总皂苷片联合双重抗血小板药物(肠溶阿司匹林+氯吡格雷)对冠状动脉药物涂层支架植入术后患者心血管事件的影响.方法 选择2010年1月至2011年12月北京安贞医院择期行雷帕霉素涂层支架植入术的急性冠状动脉综合征及稳定型心绞痛患者1200例,采用随机表法分为观察组和对照组,各600例.所有择期冠状动脉介入治疗患者均于冠状动脉造影后植入雷帕霉素药物涂层支架,术后长期口服阿托伐他汀钙20 mg/d,肠溶阿司匹林100 mg/d,氯吡格雷75 mg/d等常规治疗.观察组另加服三七总皂苷片300 mg/次,3次/d.随访观察1年,检测2组花生四烯酸(AA)和二磷酸腺苷(ADP)介导的血小板聚集率和ADP血小板聚集抑制达标率等,记录不良事件与联合用药情况,评价1年心血管事件.结果 ①观察组和对照组AA介导的血小板聚集率分别为(75±11)％、(79±10)％,组间差异无统计学意义(P＞0.05),均显示明显的抑制作用.观察组ADP介导的血小板聚集率明显高于对照组[(61±22)％比(45±20)％,P ＜0.05];观察组ADP血小板聚集抑制达标率为66.0％(396例),高于对照组[44.3％(260例)],组间差异均有统计学意义(P＜0.05).②观察组和对照组心血管事件发生率分别为3.3％(20例)和7.8％(47例),组间差异有统计学意义(P＜0.05).结论 三七总皂苷增加氯吡格雷对血小板聚集的抑制效果,减少心血管事件.     

Role of peripheral vascular resistance as an indicator of cardiovascular abnormalities in patients with Parkinson's disease

The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD ). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD , vasodilator PD , control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using impedance cardiography (ICG ) and electrocardiography (ECG ) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance. We also analyzed heart rate variability (HRV ), using spectral analysis and continuous blood pressure (contBP). At rest, the vasodilator PD group showed significantly higher values of total peripheral resistance and lower values of stroke volume and cardiac output, compared to the vasoconstrictor PD and the control groups. A post‐tilt drop in ? (change rest – tilt) systolic blood pressure, ?mean blood pressure, ?total peripheral resistance and ?Heather index, and a significantly lower increase in ?diastolic blood pressure was observed in subjects from the vasodilator PD group compared to the vasoconstrictor PD and the control groups. No statistically significant differences were observed for HRV parameters between the vasoconstrictor and vasodilator PD groups, P  > .05. Longer duration and higher disease stage of PD correlated with a reduction in post‐tilt systolic blood pressure changes in vasodilator group. Positive inotropy of the cardiac muscle represents a significant factor preventing orthostatic hypotension in PD subjects with a concurrent drop in peripheral vascular resistance during orthostatic stress.     

糖尿病患者踝臂指数与全因和心血管病死亡率关系的研究

目的研究糖尿病患者外周动脉疾病（peripheral arterial disease,PAD）踝臂指数（ankle-brachial index,ABI）与全因和心血管病（cardiovascular disease,CVD）死亡率的关系。方法研究对象来自2006年6月至2009年6月我医院的有完整ABI基线资料的糖尿病患者528例,于2006年12月至2009年12月对其进行随访调查。结果 528例糖尿病患者中,ABI降低的PAD组178例（33.71%）,ABI正常的非PAD组350例（66.29%）,血压和吸烟史是PAD的独立危险因素,在34.8个月的随访中,有33例死亡,其中17例为CVD死亡。经COX回归分析,PAD患者发生全因及CVD死亡的相对危险度分别为1.513（0.892-2.964）和4.526（0.981-13.520）。随着ABI水平降低,发生死亡及CVD死亡危险增加。结论低ABI是糖尿病患者死亡和CVD死亡的独立危险因素,在糖尿病人群中运用无创性ABI测定对全因死亡及CVD死亡具有预测价值。     

加用泮托拉唑对行双抗血小板治疗冠心病患者血小板抑制率的影响

目的 研究加用泮托拉唑对行双抗血小板治疗冠心病患者血小板抑制率的影响.方法 选取2015年7月至2016年11月本院收治的76例行双抗血小板治疗冠心病患者为研究对象,依据用药差异,分为观察组(n=38)与对照组(n=38),观察组加用泮托拉唑,对照组不加用其他药物,对比两组血小板聚集率、血小板反应指数与不良心血管事件出现率、消化道不良反应情况.结果 观察组ADP-Ag(19.08±18.36)％、不良心血管事件出现率0.00％、消化道不良反应总发生率2.63％,明显小于对照组的(28.26±20.84)％、10.53％、18.42％,且PRI为(67.43±21.13)％,明显高于对照组的(48.48±19.32)％,均P＜ 0.05.结论 对氯吡格雷条件下抗血小板治疗患者加用泮托拉唑,可产生良好血小板抑制效果,并且不会诱发心血管事件,降低消化道不良反应出现率,具有积极应用意义.     

静脉泵注右美托咪定对老年患者心血管事件及血管活性药物使用的影响

目的探究右美托咪定对老年患者围术期心血管事件及血管活性药物使用的影响。方法选取行腹腔镜手术的老年患者186例,按随机数表法分为研究组及对照组,每组各93例。研究组麻醉诱导前静脉泵注0.5μg/kg右美托咪定,后0.2μg/(kg·h)持续泵注至术毕前0.5 h;对照组泵注等容量生理盐水。比较两组围术期心血管事件发生率、血管活性药物使用次数及心率变异性[每5 min平均R-R间期标准差(standard deviation of sequential five-minute R-R interval means,SDANN)、全部窦性R-R间期标准差(standard deviation of normal R-R intervals,SDNN)、相邻R-R间期差值均方根(rootmean square standard deviations of R-R intervals,RMSSD)]。结果研究组术中及术后1 d内心血管事件总发生率分别为15.05%和4.30%,低于对照组的31.18%及12.90%(P<0.05或P<0.01)。研究组去氧肾上腺素、乌拉地尔、阿托品及艾司洛尔等血管活性药物使用次数均少于对照组(P<0.01)。术后1 d,两组SDANN、SDNN、RMSSD水平均下降,但研究组高于对照组(P<0.05)。结论静脉泵注右美托咪定可减少老年患者围术期心血管事件的发生及血管活性药物的应用,利于稳定心血管功能。     

NT-proBNP与h-FABP联合检测评价糖尿病患者发生心血管事件的相关性研究

目的探讨NT-proBNP与h-FABP联合检测在糖尿病患者发生心血管事件的相关性。方法选择来本院急诊科、内科门诊及住院部的106例2型糖尿病患者为研究对象,将所有患者根据NT-proBNP和h-FABP水平检测结果分为A组(NT-proBNP及h-FABP均升高)、B组(NT-proBNP升高,h-FABP正常)、C组(NT-proBNP正常,h-FABP升高)以及D组(NT-proBNP与h-FABP正常)。并选择同期本院健康体检者33例为对照组,监测NT-proBNP及h-FABP。随访半年后,观察随访3个月和6个月时患者心血管疾病发生情况。结果 2型糖尿病患者中的NT-proBNP及h-FABP水平增高与慢性心力衰竭、高血压以及冠心病的发生率呈正相关,且随时间的延长发生率增多,并比NT-proBNP或h-FABP两者中单一升高的2型糖尿病患者发生心血管事件危险预测将更加准确,并具有统计学意义(P0.05)。结论对2型糖尿病患者联合监测NT-proBNP及h-FABP水平可对心血管事件做出准确的危险预测具有重要意义。     

Xuezhikang, an extract of cholestin, reduces cardiovascular events in type 2 diabetes patients with coronary heart disease: subgroup analysis of patients with type 2 diabetes from China coronary secondary prevention study (CCSPS)

Lipid-lowering therapy has been proven to reduce macrovascular complications of type 2 diabetes. Xuezhikang is an extract of cholestin and has a markedly modulating effect on lipids, but the effect of xuezhikang on reducing coronary events in diabetic patients with coronary heart disease (CHD) is less clear. A total of 591 diabetic patients with CHD were randomized to the xuezhikang group (n=306) and the placebo group (n=285). During the average 4 years of follow-up, there were 28 cases of CHD events (9.2%) in the xuezhikang group and 53 cases (18.6%) in the placebo group. Risk reduction for CHD events was 50.8% (P<0.001) by xuezhikang treatment. Xuezhikang decreased the risk of non-fatal MI by 63.8%, fatal MI by 58.5%, CHD sudden death by 26.9%, and other CHD death by 53.4%. CHD death totaled to 21 cases in the xuezhikang group (6.9%) and 35 cases in the placebo group (12.3%), indicating that xuezhikang significantly decreased the risk of CHD death by 44.1% (P<0.05). Seventy-two patients died from various causes, among which there were 27 patients in the xuezhikang group and 45 patients in the placebo group. The risk for all-cause death was 44.1% lower in the xuezhikang group than in the placebo group (P<0.01). This investigation demonstrates that xuezhikang therapy can be effective on reduction of cardiovascular events in diabetic patients with CHD with a reliable safety.     

冠心病合并糖尿病患者应用罗格列酮对心血管事件发生的影响

目的分析冠心病合并糖尿病患者应用罗格列酮治疗对心血管事件发生率的影响。方法回顾性分析本科住院106例冠心病合并糖尿病患者,依据治疗方案差异分为两组：对照组52例．予以常规治疗：研究组54例,常规治疗联合应用罗格列酮。随访1年,比较两组的主要心血管事件（MACE）发生率的差异,如：接受血运重建术、心肌梗死、充血性心力衰竭、脑卒中以及心源性猝死。结果与对照组相比,研究组的充血性心力衰竭发生率显著升高（P〈0．05）,但是接受血运重建术、心肌梗死、脑卒中以及心源性猝死等MACE的发生率虽有升高,但差异无统计学意义（P〉0．05）。结论冠心病合并糖尿病患者应用罗格列酮治疗对缺血性MACE无明显影响,但能增加充血性MACE风险。     

Association of serum osteocalcin levels with major adverse cardiovascular events: A 4.4‐year retrospective cohort study

We investigated whether the serum osteocalcin levels at baseline were associated with the incidence of major adverse cardiovascular events (MACE) in a population‐based retrospective cohort study of Chinese subjects. Coronary angiography was used to diagnose coronary artery disease (CAD). Survival curves were analyzed by performing log‐rank tests with Kaplan‐Meier figures. Multivariable Cox proportional hazards regression was performed to identify the association of serum osteocalcin levels with the incidence of MACE. A total of 247 subjects with a mean age of 65.50 ± 10.38 years were enrolled in the analysis. After a mean follow‐up time of 4.4 ± 2.6 years, MACE occurred in 175 cases. For men patients, those with serum osteocalcin levels higher than 17.22 ng/mL had significantly lower fasting plasma glucose (FPG) than those with serum osteocalcin levels lower than 17.22 ng/mL (P < .05). According to the multivariate Cox proportional hazards regression, the lower serum osteocalcin levels and the higher risk of future MACE occurred in men with CAD at baseline (hazard ratio = 0.970; 95% confidence interval 0.943‐0.999, P = .04). However, this difference was not significant either in men without CAD or in women. In conclusion, relatively lower serum osteocalcin levels were associated with a higher risk of MACE in Chinese men with CAD.     

双抗血小板联合阿托伐他汀治疗对高龄冠心病PCI术患者颈动脉硬化斑块及心肌功能的影响

目的 观察双抗血小板联合阿托伐他汀治疗对高龄冠心病经皮冠状动脉介入治疗(PCI)术患者颈动脉硬化斑块及心肌功能的影响.方法 将2014年1月至2016年2月本院收治的66例高龄冠心病PCI术患者随机数字表法均分为研究组和对照组,两组均实施双抗血小板治疗,研究组另给予阿托伐他汀治疗,观察两组治疗前后颈动脉硬化斑块[颈动脉内中膜厚度(IMT)、斑块面积(PA)]、心肌功能指标[肌酸激酶同工酶(CKMB)、肌钙蛋白Ⅰ(cTNⅠ)]及治疗期间不良心血管事件发生率.结果 两组治疗结束后IMT、PA均较治疗前显著减小,且治疗结束后研究组IMT、PA较对照组显著减小,差异均有统计学意义(均P＜ 0.05);治疗结束后仅对照组CKMB、cTNⅠ较治疗前显著升高,且治疗结束后研究组CKMB、cTNⅠ显著低于对照组(P＜0.05);治疗期间研究组不良心血管事件总发生率较对照组显著低(P＜0.05).结论 双抗血小板联合阿托伐他汀治疗可显著减小高龄冠心病PCI术患者的颈动脉硬化斑块,且有效减轻对心肌功能损害程度.     

早期应用丁苯酞联合低分子肝素、双联抗血小板聚集药物治疗急性穿支动脉病变型脑梗死的疗效及安全性分析

目的观察早期应用丁苯酞联合低分子肝素、双联抗血小板聚集药物治疗急性穿支动脉病变型脑梗死的疗效及安全性。方法503例急性穿支动脉病变型脑梗死患者,随机分为对照组(253例)和研究组(250例)。对照组患者给予低分子肝素、双联抗血小板聚集药物进行治疗,研究组在对照组基础上给予丁苯酞进行治疗。观察比较两组患者治疗前和治疗1、7 d后神经功能缺损程度,治疗前和治疗3个月后生活能力,不良反应发生情况。结果两组患者治疗1、7 d后美国国立卫生研究院卒中量表(NIHSS)评分均低于本组治疗前,差异具有统计学意义(P<0.05)。治疗1 d后,研究组NIHSS评分(14.63±1.34)分略低于对照组的(14.77±1.48)分,但差异无统计学意义(P>0.05);治疗7 d后,研究组患者NIHSS评分(8.03±1.54)分明显低于对照组的(11.56±2.01)分,差异具有统计学意义(P<0.05)。两组患者治疗3个月后改良RANKIN量表(mRS)评分均低于本组治疗前,差异具有统计学意义(P<0.05)。治疗3个月后,研究组患者mRS评分(0.98±0.34)分明显低于对照组的(1.77±0.48)分,差异具有统计学意义(P<0.05)。两组患者治疗过程中均无肠道出血等不良反应发生。结论早期应用丁苯酞联合低分子肝素、双联抗血小板聚集药物治疗急性穿支动脉病变型脑梗死患者,可有效改善患者的神经功能损伤状态,恢复患者生活能力,且安全性较好,具有较高的推广价值。     

Abnormal lipids in high-risk patients achieving cholesterol targets: a cross-sectional study of routinely collected UK general practice data

ABSTRACT

Background and objectives: Lipid management in UK general practice targets the achievement of total cholesterol (TC) targets in high-risk individuals. Statins alone have a modest effect on non-LDL-C components of the lipid profile, leaving these patients at significant residual cardiovascular (CV) risk. Improving risk further would require the addition of non-statin therapies. This analysis explores what proportion of the UK population with cardiovascular disease (CVD) and TC levels at or below target may still be at risk because of residual dyslipidaemia.

Methods: CV risk profiles were extracted from a research database of 602?222 patients from 98 UK general practices. Patients were categorised according to their prior CV history and use of statins. Mean values and proportions achieving treatment targets were assessed for TC, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglycerides (TG).

Results: In all, 48?499 patients with pre-existing CVD or diabetes were identified. 73% of statin-treated patients and 63% of untreated patients had a TC ≤?5?mmol/L. 28.6% of patients treated to a TC target had LDL-C?> 3?mmol/L. Amongst those with both TC and LDL-C treated to target, 22.5% had low HDL-C and 37.2% had high triglyceride (TG). Within this group, more women than men had abnormal HDL-C (25.4?vs. 20.7% p?< 0.0001). Patients with diabetes were more likely than non-diabetics to have abnormalities of both HDL-C (28.9?vs. 16.4% p?< 0.0001) and triglyceride (44.9?vs. 29.5% p?< 0.0001) despite normal TC and LDL-C.

Conclusions: Around 60% of high-risk patients have residual dyslipidaemias despite achieving the Quality and Outcomes Framework (QOF) TC target. New patterns of treatment are required in order to extend lipid management beyond simple total cholesterol lowering.     

达格列净对2型糖尿病患者心血管安全性影响的Meta分析

目的：评价达格列净对2型糖尿病患者心血管安全性的影响。方法以“达格列净”、“sodium-glucose cotransporter 2 inhibitor*”、“SGLT2 inhibitor*”、“dapagliflozin”和“BMS 512148”为关键词,检索PubMed（截至2013年11月）和Cochrane图书馆、Embase、中国知网、万方数据库（截至2013年10月）,筛选达格列净对2型糖尿病患者心血管事件影响的随机对照试验（ RCT）。干预措施包括达格列净与安慰剂或其他降糖药物比较,以及达格列净联合其他降糖药物与相同降糖药物联合安慰剂或另一种降糖药物比较。结局指标主要终点为主要不良心血管事件（ MACE）,次要终点为心肌梗死、卒中、全因死亡和心血管死亡。使用 RevMan5.2软件进行 Meta 分析。计数资料采用Mantel-Haenszel方法检验,计算比值比（ OR）及95%置信区间（ CI）。结果共11项RCT纳入Meta分析。达格列净组MACE发生率（0.39%,5/1271）与安慰剂组（0.54%,3/551）比较差异无统计学意义（OR=0.65,95%CI为0.16~2.65,P=0.55）,达格列净组MACE发生率（0.24%,1/422）与二甲双胍组（0.24%,1/409）比较差异无统计学意义（OR=0.97,95%CI为0.14~6.88,P=0.98）。达格列净组卒中发生率（0.28%,3/1060）与安慰剂组（0.29%,1/343）比较差异无统计学意义（ OR =0.76,95%CI为0.11~5.14,P =0.77）。达格列净组全因病死率（0.26%,6/2278）与安慰剂组（0.18%,2/1082）比较差异无统计学意义（OR=0.91,95%CI为0.30~2.75,P=0.86）,达格列净组全因病死率（0.24%,1/422）与二甲双胍组（0.24%,1/409）比较差异无统计学意义（ OR=0.97,95%CI为0.14~6.88,P=0.98）。达格列净组心血管病死率（0.24%,3/1271）与安慰剂组（0.18%,1/551）比较差异无统计学意义（OR=0.81,95%CI为0.16~4.27,P=0.81）,达格列净组心血管病死率（0.24%,1/422）与二甲双胍组（0.24%,1/409）比较差异无统计学意义（ OR =0.97,95%CI 为0.14~6.88,P=0.98）。结论达格列净不增加2型糖尿病患者MACE风险。     

Esomeprazole and rabeprazole did not reduce antiplatelet effects of aspirin/clopidogrel dual therapy in patients undergoing percutaneous coronary intervention: a prospective,randomized, case–control study

Objectives: Controversy has been prompted based on drug interaction between proton pump inhibitors (PPIs) and aspirin/clopidogrel leading to weakened effects. However, whether such interaction was drug-specific or class effect remains controversial. This study predicted the impact of esomeprazole and rabeprazole on efficacy of dual antiplatelet therapy (DAPT).

Methods: This study, involving 150 patients, evaluated the efficacy of DAPT upon concomitant use of esomeprazole (40 mg/d) or rabeprazole (20 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at day 1, day 3 and day 30 end points after initiation of DAPT.

Results: No significance were observed by post-hoc analysis of treatment-by-period interaction in LTA value and VASP-PRI value when compared with non-PPI users, which suggests no carryover effect in both PPIs over the 30-day treatment period. Moreover, no statistical differences was in LTA or VASP-PRI value in esomeprazole group while rabeprazole group showed decreased in antiplatelet function of DAPT at the day 3 and day 30 end points.

Conclusion: Although antiplatelet effect of DAPT were not affected upon concomitant use of both PPIs over the 30-day treatment period, esomeprazole exerts much more stable impact on antiplatelet effect than rabeprazole among respective end points.     

Dapagliflozin: potential beneficial effects in the prevention and treatment of renal and cardiovascular complications in patients with type 2 diabetes

Introduction: Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects.

Areas covered: This review examines the role of the kidney in glucose homeostasis, discusses renal hemodynamic changes in diabetes, and outlines the major hypotheses regarding the mechanisms underlying renal injury in diabetes. The potential benefits of SGLT2 inhibitors in the prevention and treatment of CV complications in patients with T2DM are reviewed, with particular focus on dapagliflozin.

Expert opinion: Dapagliflozin and other SGLT2 inhibitors have the capacity to decrease hyperglycemia and visceral fat, components of the metabolic syndrome particularly associated with the progression of CV disease. However, the mechanisms of action of SGLT2 inhibitors resulting in their positive CV effects remain unclear. Furthermore, the mechanism of action of SGLT2 inhibitors on heart function in non-diabetic patients with decompensated heart failure remains to be explored.