应用血栓弹力图评估高龄老年冠心病氯吡格雷抵抗患者服用替格瑞洛的疗效

目的通过血栓弹力图(TEG)监测ADP诱导的血小板抑制率,观察高龄老年冠心病患者口服氯吡格雷抵抗时更换为替格瑞洛的疗效。方法选择自2012年10月~2014年12月于北京军区总医院干部病房一、四科及心血管内科住院的75岁以上老年急性冠脉综合征(ACS)及经皮冠状动脉介入(PCI)术后氯吡格雷抵抗的患者31例(ACS10例,PCI术后21例),其中男性27例,女性4例。分为氯吡格雷组(15例)及替格瑞洛组(16例),氯吡格雷组继续服用氯吡格雷(75 mg 1/日),替格瑞洛组更换为替格瑞洛(90 mg 2/日),连续治疗8周。分别于服药前、服药后1、4、8周观察ADP诱导的血小板抑制率的变化,并比较两组主要不良心血管事件的发生情况。结果与氯吡格雷组比较,替格瑞洛组治疗1周、4周以及8周后,ADP诱导的血小板抑制率升高,为[(22.6±4.5)%vs.(35.8±5.7)%]、[(21.9±4.6)%vs.(36.9±5.5)%]、[(22.8±4.6)%vs.(37.1±5.2)%],差异有统计学意义(P均0.05)。氯吡格雷组心肌梗死1例,再发心绞痛5例,总计6例(40%);替格瑞洛组轻度呼吸困难1例,未做特殊处理3 d后呼吸困难缓解,再发心绞痛1例,总计1例(6.3%)。氯吡格雷组主要不良心血管事件发生率较替格瑞洛组升高(40%vs.6.3%),差异有统计学意义(P0.05)。结论高龄老年冠心病氯吡格雷抵抗患者将氯吡格雷更换为替格瑞洛,明显升高ADP诱导的血小板抑制率,减少主要不良心血管事件,具有良好的安全性和耐受性。     

不同抗血小板治疗对经皮冠状动脉介入术后氯吡格雷抵抗患者血小板miR-223、血小板抑制率及血小板活化指标的影响

目的:探讨不同抗血小板治疗方案对经皮冠状动脉介入术(PCI)后氯吡格雷抵抗患者血小板微小RNA-223(miR-223)、血小板抑制率及血小板活化指标的影响。方法:将160例PCI后氯吡格雷抵抗患者随机分为氯吡格雷双倍组(n=80,氯吡格雷150 mg,每日1次)和替格瑞洛组(n=80,替格瑞洛90 mg/次,每日2次)。比较两组治疗前后血小板抑制率、血小板miR-223、血小板α颗粒表面膜糖蛋白(CD62P)、活化血小板糖基化复合物(PAC-1)的变化。随访6个月,记录两组主要不良心血管事件(MACE)、出血事件及呼吸困难的发生情况。结果:治疗7 d、30 d后,替格瑞洛组血小板抑制率均明显高于氯吡格雷双倍组(P均0.05)。治疗30 d后,替格瑞洛组血小板miR-223、CD62P、PAC-1表达水平均明显低于氯吡格雷双倍组(P均0.05)。随访6个月,替格瑞洛组MACE发生率明显低于氯吡格雷双倍组(3.75%对13.75%,P0.05);两组出血事件发生率的差异无统计学意义,但替格瑞洛组呼吸困难发生率明显高于氯吡格雷双倍组(11.25%对16.25%,P0.05)。结论:对于PCI后氯吡格雷抵抗的冠状动脉粥样硬化性心脏病患者,替格瑞洛较双倍剂量氯吡格雷能够更好地抑制血小板聚集,减少MACE,且不增加出血风险。但替格瑞洛易引起呼吸困难,临床应予以足够重视。     

老年女性急性冠状动脉综合征行介入治疗患者应用氯吡格雷和替格瑞洛一年的临床结局

目的观察老年女性急性冠状动脉综合征(acute coronary syndrome, ACS)行PCI的患者应用双联抗血小板治疗1年的临床结局。方法入选2016年1月～2017年12月因ACS首次入我院且行PCI的老年女性患者284例,随机分为氯吡格雷组129例和替格瑞洛组155例,2组均服用阿司匹林,分别加服氯吡格雷或替格瑞洛,用比浊法检测血小板聚集率,平均随访1年,比较2组患者血小板聚集率、支架内血栓和出血事件。结果 2组花生四烯酸诱导的血小板聚集率比较无统计学差异(P0.05);氯吡格雷组二磷酸腺苷诱导的血小板聚集率高于替格瑞洛组[(36.43±23.17)%vs(13.88±11.48)%,P0.05];氯吡格雷组与替格瑞洛组支架内血栓(0.8%vs 0.6%)、TIMI定义的大出血(0.8%vs 2.6%)、颅内出血(0.8%vs 1.3%)发生率比较,均无统计学差异(P0.05),替格瑞洛组TIMI定义的少量出血(7.7%vs 1.6%)及不明显出血(9.0%vs 2.3%)发生率明显高于氯吡格雷组(P0.05),氯吡格雷组与替格瑞洛组出血事件发生率比较,差异有统计学意义(4.7%vs 19.4%,P0.01)。结论 ACS患者用替格瑞洛的支架内血栓与氯吡格雷无统计差异,出血事件中,主要是少量出血及不明显出血较氯吡格雷增加。     

替格瑞洛与氯吡格雷对急性冠脉综合征患者PCI术后血小板功能和炎症因子的影响

目的比较替格瑞洛和氯吡格雷对急性冠脉综合征(ACS)患者经皮冠状动脉介入(PCI)术后血小板功能和炎症因子的影响。方法入选2013年1月~2014年2月于新乡市第二人民医院心血管内科接受冠状动脉造影确诊为ACS患者84例,其中男性52例,女性32例,年龄50~71(60.48±8.96)岁。按入院顺序随机分为替格瑞洛组和氯吡格雷组,每组各42例。替格瑞洛组应用阿司匹林+替格瑞洛抗血小板治疗;氯吡格雷组应用阿司匹林+氯吡格雷抗血小板治疗。两组患者均观察治疗12个月。于治疗前、术后24 h、术后7 d、术后28 d检测血小板最大聚集率(MPAR)、P2Y_(12)反应单位(PRU)、可溶性白细胞分化抗原40配体(s CD40L)、高敏C反应蛋白(hs-CRP),并监测药物的不良反应。随访12个月的缺血事件和出血事件。结果术后24 h、术后7 d、术后28 d替格瑞洛组患者的MPAR及PRU均显著低于氯吡格雷组,差异有统计学意义(P均0.01)。两组患者炎症因子水平均在术后24 h出现峰值,随后下降。术后24 h、7 d、28 d替格瑞洛组患者的hs-CRP和s CD40L水平均低于氯吡格雷组,差异有统计学意义(P均0.05)。随访12个月内,替格瑞洛组缺血事件发生率低于氯吡格雷组(2.38%vs.19.05%),差异有统计学意义(P0.05)。结论 ACS患者PCI术后应用替格瑞洛抗血小板聚集和炎症反应优于氯吡格雷,并降低缺血事件发生率。     

急性冠状动脉综合征合并2型糖尿病患者冠状动脉介入术后替格瑞洛与氯吡格雷抗血小板疗效及预后

目的应用血栓弹力图(TEG)评价替格瑞洛与氯吡格雷在急性冠状动脉综合征(ACS)合并糖尿病患者经皮冠状动脉介入治疗(PCI)后抗血小板的疗效及预后。方法纳入ACS合并糖尿病行PCI术的患者180例。随机分为两组,氯吡格雷组(n=92)术前接受负荷量阿司匹林300 mg+氯吡格雷300 mg,术后给予阿司匹林100mg/d,氯吡格雷75 mg/d;替格瑞洛组(n=88)术前接受负荷量阿司匹林300 mg+替格瑞洛180 mg,术后给予阿司匹林100 mg/d,替格瑞洛90 mg,每天两次。血栓弹力图检测两组患者PCI术后24 h花生四烯酸(AA)诱导的血小板抑制率和二磷酸腺苷(ADP)诱导的血小板抑制率,观察并比较两组3个月内不良心血管事件及出血等安全性事件。结果替格瑞洛组ADP激活血小板形成最大血凝块强度(MA-ADP),低于氯吡格雷组(34.94%±11.91%比47.16%±14.90%,P0.001)。血小板AA抑制率、ADP抑制率替格瑞洛组明显高于氯吡格雷组(68.24%±22.96%比48.21%±32.91%,58.16%±23.52%比33.34%±26.67%,P0.001)。结论 ACS合并2型糖尿病患者中,替格瑞洛抗血小板聚集的效果明显优于氯吡格雷,可显著降低3个月内心血管终点事件的发生率,不增加出血风险。     

急性冠状动脉综合征合并糖尿病患者经皮冠状动脉介入术后替格瑞洛与氯吡格雷抗血小板疗效及预后研究

目的应用血栓弹力图评价替格瑞洛与氯吡格雷在急性冠状动脉综合征(ACS)合并糖尿病(DM)患者经皮冠状动脉介入(PCI)术后抗血小板治疗的疗效和预后。方法入选2016年6月至2017年1月期间在陕西省第四人民医院心血管内科住院治疗的ACS合并DM患者100例。采用前瞻性、随机对照的研究方法,按随机数字表分为两组:氯吡格雷组和替格瑞洛组,每组50例。PCI术后24~48 h行血栓弹力图检测,比较两组花生四烯酸(AA)诱导的血小板抑制率和二磷酸腺苷(ADP)诱导的血小板抑制率以及最大血凝块幅度(MAADP)。术后随访6个月,比较两组主要不良心血管事件(MACE)、出血事件和呼吸困难的发生率。采用SPSS 19.0软件进行数据处理。根据数据类型,分别采用t检验或x~2检验进行组间比较。结果与氯吡格雷组相比,替格瑞洛组AA抑制率[(72.3±26.6)%vs(54.0±31.4)%,P=0.041]和ADP抑制率[(76.5±22.1)%vs(43.4±28.7)%,P=0.016]均显著增高,MAADP幅度显著降低[(33.2±10.5)vs(48.2±13.6)mm,P=0.024]。替格瑞洛组AA抑制率50%(14.0%vs38.0%,P=0.006)和ADP抑制率30%(6.0%vs28.0%,P=0.003)的患者数量显著低于氯吡格雷组。术后6个月替格瑞洛组MACE发生率较氯吡格雷组显著降低(8.2%vs 22.9%,P=0.045);两组出血事件和呼吸困难发生率间差异无统计学意义。结论对于ACS合并DM患者,PCI术后服用替格瑞洛的抗血小板疗效明显优于氯吡格雷。     

替格瑞洛与氯吡格雷序贯治疗对STEMI急诊PCI患者血小板聚集率及MACE的影响

目的探讨行急诊经皮冠状动脉介入治疗(PCI)急性ST段抬高型心肌梗死(STEMI)患者替格瑞洛与氯吡格雷序贯治疗对血小板聚集率及主要不良心血管事件(MACE)的影响。方法选择2012年2月~2015年3月黑龙江佳木斯市中心医院心内科收治急性STEMI并行急诊PCI治疗的患者92例,随机分为替格瑞洛组(n=30)、氯吡格雷组(n=30)与序贯治疗组(n=32)3组。替格瑞洛组给予替格瑞洛口服;氯吡格雷组给予氯吡格雷口服;序贯治疗组先给予替格瑞洛口服,7 d后更改为氯吡格雷口服。检测急诊PCI术前及术后2 h、24 h、7 d及30 d时血小板聚集率,并观察患者30 d内MACE及出血事件的发生率。结果 3组患者急诊PCI术后血小板聚集率较术前均明显下降(P0.05);在术后2 h、24 h、7 d时间点替格瑞洛组血小板聚集率与氯吡格雷组比较下降更明显(P0.05);在术后2 h、24 h、7 d、30 d时间点序贯治疗组与替格瑞洛组血小板聚集率差异无统计学意义(P0.05);替格瑞洛组与序贯治疗组30d内MACE事件发生率均低于氯吡格雷组(P0.05);住院期间3组出血事件发生率差异无显著性(P0.05)。结论 STEMI患者行急诊PCI术前应用替格瑞洛抗血小板治疗,可显著抑制血小板聚集,降低30 d内MACE事件且不增加出血风险;STEMI患者PCI术一周后口服氯吡格雷替代替格瑞洛具有与替格瑞洛同样的疗效。     

替格瑞洛治疗氯吡格雷抵抗性急性冠脉综合征患者的临床效果

目的:研究替格瑞洛治疗氯吡格雷抵抗性急性冠脉综合征(CPGR-ACS)患者的临床效果。方法:于我院行经皮冠状动脉介入治疗(PCI)且术后发生CPGR-ACS的患者138例被随机分为常规治疗组(69例,强化氯吡格雷+拜阿司匹林治疗)与替格瑞洛组(69例,替格瑞洛+拜阿司匹林治疗)。连续治疗90d,观察两组治疗前后血小板抑制率(PIR),血清基质金属蛋白酶2(MMP-2)、hsCRP水平,心率变异性(HRV),主要心血管不良事件(MACE)及出血事件。结果:治疗后,与常规治疗组比较,替格瑞洛组血小板抑制率[(25.76±4.63)%比(43.97±6.43)%]显著提高,血清MMP-2[(44.85±4.51)ng/ml比(36.96±3.72) ng/ml]、hsCRP[(11.64±1.2)mg/L比(7.15±0.72)mg/L]水平显著降低,HRV指标中SDNN[(62.87±6.33)ms比(96.86±9.72)ms]、SDANN[(37.62±3.81)ms比(46.38±4.72)ms]、rMSSD[(25.70±2.61)ms比(38.27±3.93)ms]、PNN50[(3.61±0.37)%比(4.93±0.51)%]、HF[(163.27±16.42)ms~2比(178.68±18.21) ms~2]值均显著增加, LF[(283.62±28.90) ms~2比(197.32±20.18) ms~2]显著减小(P均=0.001)。替格瑞洛组MACE发生率显著低于常规治疗组(2.90%比15.94%,P=0.009)。两组出血事件比较无显著差异(P=0.229)。结论:替格瑞洛治疗氯吡格雷抵抗性急性冠脉综合征患者,疗效显著,安全可靠。     

替格瑞洛与氯吡格雷在急性心肌梗死患者经皮冠状动脉介入治疗中有效性和安全性的对比研究

目的比较替格瑞洛与氯吡格雷在急性心肌梗死(AMI)患者经皮冠状动脉介入治疗(PCI)中的有效性和安全性。方法选取2014年1月—2015年5月郑州市第一人民医院心内科收治的AMI患者203例,随机分为替格瑞洛组90例和氯吡格雷组113例。在常规治疗及PCI基础上,替格瑞洛组患者给予替格瑞洛治疗,氯吡格雷组患者给予氯吡格雷治疗;两组患者均规律服药12个月。比较两组患者PCI前和PCI后1、6、12个月血小板计数、血小板最大聚集率、尿酸、肌酐及治疗期间不良事件发生情况(包括胸闷、缺血事件、出血事件)。结果时间与方法在血小板计数、肌酐上无交互作用(P>0.05);时间在血小板计数、肌酐上主效应不显著(P>0.05);方法在血小板计数、肌酐上主效应不显著(P>0.05)。时间与方法在血小板最大聚集率、尿酸上存在交互作用(P<0.05);时间在血小板最大聚集率、尿酸上主效应显著(P<0.05);方法在血小板最大聚集率、尿酸上主效应显著(P<0.05);PCI后1、6、12个月替格瑞洛组患者血小板最大聚集率低于氯吡格雷组,PCI后6、12个月替格瑞洛组患者尿酸高于氯吡格雷组(P<0.05)。替格瑞洛组患者治疗期间胸闷、出血事件发生率高于氯吡格雷组,缺血事件发生率低于氯吡格雷组(P<0.05)。结论与氯吡格雷相比,替格瑞洛能更好地抑制AMI患者PCI后血小板聚集,但高尿酸血症、胸闷、出血发生风险较高,应加以重视。     

血栓弹力图评估PCI后氯吡格雷不敏感患者抗血小板药物的疗效

目的应用血栓弹力图(TEG)评估冠状动脉粥样硬化性心脏病(冠心病)患者行经皮冠状动脉介入治疗(PCI)后氯吡格雷不敏感患者中不同抗血小板药物的疗效。方法对在应急总医院心内科行PCI并规律服用阿司匹林及氯吡格雷的冠心病患者278例,通过TEG检测血小板抑制率,ADP抑制率≥50%为达标组,ADP抑制率50%为未达标组;未达标组随机将氯吡格雷更换为替格瑞洛,为替格瑞洛组,应用氯吡格雷的患者为氯吡格雷组,分析替格瑞洛组换药前后AA抑制率和ADP抑制率的变化及其与达标组的差异,随访患者1年内呼吸困难、出血等不良反应。结果替格瑞洛组将氯吡格雷更换为替格瑞洛后ADP抑制率及AA抑制率均较前升高,差异有统计学意义(P0.05);替格瑞洛组换药前ADP抑制率和AA抑制率低于达标组,差异有统计学意义(P0.05),换药后ADP抑制率和AA抑制率与达标组相比,差异无统计学意义(P0.05);随访1年内两组均无严重出血及小出血事件发生,替格瑞洛组轻度呼吸困难发生率增多(P0.05),两组间轻微出血的发生无统计学差异(P0.05)。结论 TEG评估发现在PCI后对氯吡格雷不敏感(ADP抑制率50%)的患者中,替格瑞洛可以提高血小板在ADP途径和AA途径中对抗血小板药物的反应性,与对氯吡格雷敏感患者相比无明显差异。     

Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma

The bronchodilator effect of nebulized AMN, albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children. In phase 1, maximal bronchodilation was determined by dose-response studies on separate days. Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2. In phase 1, 0.11 +/- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation. In phase 2, the peak response to albuterol occurred within 30 min and to AMN, at 60 min. Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol. AMN FEV1 response was better than for placebo for 3 h; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus, the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children, but the combination may extend the period of bronchodilatation.     

Perception of bronchodilation in subjects with asthma and smokers with airflow limitation

Perception of the efficacy of bronchodilators in relieving airflow obstruction is a likely determinant of compliance with treatment in patients prescribed these drugs on an 'as needed' basis. This study aimed to determine whether bronchodilator-induced improvements in lung function are associated with improvements in breathing difficulty in subjects with asthma or smokers with airflow limitation. Twenty smokers with airflow limitation and 16 subjects with previously physician-diagnosed asthma received salbutamol (200 micrograms) and ipratropium bromide (80 micrograms). Spirometry and lung volumes were measured before and 40 min after bronchodilator. Subjects recorded changes in 'difficult breathing' on a visual analogue scale (VAS). After bronchodilator, forced expiratory volume in 1 s (FEV1) increased by 23.0 +/- 6.4% of baseline (mean +/- 95% CI) in smokers, and by 25.2 +/- 8.5% in the asthmatics, while VAS improved by 31 +/- 23% in smokers and 45 +/- 25% in asthmatics. However, these changes were not significantly correlated in either smokers (r = -0.04) or asthmatics (r = 0.15). In the asthmatic subjects, good perceivers (> 25% improvement in VAS) had greater improvements in lung volumes, as percentage predicted, than did poor perceivers. In the smokers, changes in lung function did not differ significantly between good and poor perceivers. Improvement in FEV1, as percentage predicted, was significantly correlated with improvement in VAS in good perceivers (asthma: r = 0.78, P < 0.01; smokers: r = 0.68, P < 0.05), but not in poor perceivers. Asthmatic subjects had good perception of improvements in lung function. However, in smokers with airflow limitation there is little correlation between improvement in lung function and sensation of breathing difficulty. In these subjects symptoms appear to be an unreliable guide for 'as needed' use of bronchodilators.     

Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia

We administered the anti-angiogenic drug thalidomide to 21 patients (12 men) with myelofibrosis with myeloid metaplasia (MMM), who were not responsive to standard treatment. Patients received thalidomide at an escalating dose from 100 to 400 mg/d. Administration of the drug was discontinued before the planned 6 months of treatment in 19 patients (90.5%), mainly because of somnolence and/or fatigue, neurological symptoms or neutropenia. Of the 13 evaluable patients (who received more than 30 d of therapy), anaemia improved in three out of seven (43%) who were treated because of anaemia; thrombocytopenia improved in two out of three (66.6%) who were treated because of thrombocytopenia; splenomegaly was reduced in four (30.8%). Undesired increases in white blood cell and platelet counts were observed in three (23.1%) and five (38.5%) patients respectively. A severity score, indexed on haematological and clinical parameters, improved in two patients (15.4%), but worsened in five (38.5%). In conclusion, standard-dose thalidomide in MMM patients is burdened with a high rate of side-effects, which prevent prolonged treatment. Because the drug is effective in improving anaemia and thrombocytopenia and in reducing splenomegaly, low-dose therapy warrants evaluation. The unexpected observation of leucocytosis and thrombocytosis suggests biological studies and better criteria for selection of patients for treatment.     

Ploidy pattern of megakaryocytes in patients with metastatic tumors with and without paraneoplastic thrombosis and in controls

In order to measure megakaryocyte DNA content in a greater number of well-defined patients, the use of bone marrow aspirates obtained postmortem is a basic requirement. We could show that the distinction between the ploidy classes in DNA histograms is possible until 18 h postmortem. Thus, bone marrow aspirates obtained up to 12 h after death can be expected to give reliable results. Megakaryocytes of the following patient groups were studied: 15 patients with metastatic tumors and paraneoplastic thrombosis, 15 patients with metastatic tumors without paraneoplastic thrombosis and 10 controls. A higher ploidy of the megakaryocytes was found in all 30 patients with metastatic tumors, independently of whether these patients suffer from thrombosis or not. Higher megakaryocyte ploidy, however, is correlated with a larger cytoplasmic mass of megakaryocytes, which leads to an increased platelet production. Besides an overcompensation for increased platelet consumption, a mitogenic or thrombopoietin-like factor produced by the tumor itself must be considered.