TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction

Purpose

The purpose of the study was to evaluate the cause of death, risk of nonfatal complications, and relative outcomes with an enoxaparin versus unfractionated heparin strategy in ST-elevation myocardial infarction stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI).

Methods

We evaluated 30-day outcomes in 19,941 patients with ST-elevation myocardial infarction treated with fibrinolysis and unfractionated heparin or enoxaparin. Patients were categorized on the basis of prespecified ranges of the TRI [heart rate × (age/10)²/systolic blood pressure].

Results

There was a strongly graded increase in 30-day mortality with increasing TRI (1.2%-20.7%, P <.0001). The proportion of deaths due to mechanical causes (congestive heart failure, shock, and myocardial rupture) increased progressively with the TRI. There also was a significant positively graded association between the TRI and nonfatal heart failure or shock (0.4%-4.4%, P <.0001). In contrast, death resulting from recurrent ischemic events predominated in the lowest TRI group. The relative reduction in death/myocardial infarction with the enoxaparin strategy appeared inversely graded with the TRI. There was a 38% reduction in the lowest risk group (relative risk 0.62, 95% confidence interval 0.45-0.86) and a decrease in the relative benefit of enoxaparin with increasing risk index.

Conclusions

The TRI was a strong predictor of all-cause mortality in a broad population, with a positive association with the risk of death due to mechanical complications and an inverse association with deaths due to recurrent ischemia. The enoxaparin strategy was superior to unfractionated heparin in a majority of patients with ST-elevation myocardial infarction, except for the group at the highest risk for severe mechanical complications, in whom the 2 anticoagulant strategies showed similar results.     

2019—2021年复旦大学附属妇产科医院低分子肝素的使用合理性分析

目的 分析2019—2021年复旦大学附属妇产科医院住院患者低分子肝素的使用情况，并评价其合理性，为妇产科低分子肝素合理性使用提供数据资料。方法 采用回顾性研究方法，从复旦大学附属妇产科医院住院医院信息系统（HIS）中查询2019年1月—2021年12月使用低分子肝素的病史信息，包含患者年龄、科室、出入院诊断、手术名称、药品名称及规格、使用频次、单次剂量和给药途径等。结果 2019—2021年使用低分子肝素的患者共54 138例，其中产科14 068例，妇科40 070例。产科年龄分布在19～35岁，妇科年龄分布在41～60岁。诊断为静脉血栓栓塞的患者共102例，妇科患者居多，占比90.20%。预防用药方面，产科剖宫产患者居多，占比63.25%；妇科为手术患者，占比98.06%，妇科恶性肿瘤的患者占比26.28%。产科及妇科患者预防用药和治疗性用药疗程主要集中在1～7 d，不合理的用法用量主要表现为给药途径不合理、单次剂量超限和给药频次不合理等，共64例，占比0.12%。结论 2019—2021年复旦大学附属妇产科医院低分子肝素的使用以预防使用为主。产科以剖宫产患者为主，妇科以手术患者为主，用法用量基本合理。     

依诺肝素治疗老年不稳定型心绞痛30例近期疗效观察

目的：观察依诺肝素治疗老年不稳定型心绞痛的近期疗效。方法：将55例老年不稳定心绞痛患者随机分为2组,分别观察依诺肝素组治疗前后心绞痛发作频率,心电图及动态心电图变化和急性心肌梗死,急性血管再通术,院内死亡发生率;并与普通肝素组相对照。结果：依诺肝素组患者心绞痛发作频率明显减少,心电图缺血明显改善;与对照组比较存在明显差异（P＜0．05）,急性心肌梗死,急性血管再通术,院内死亡主要事件总发生率为6．66％,对照组为16％,2组比较差异显著,2组均无严重出血,结论：依诺肝素治疗老年不稳定型心绞痛疗效确切。安全。     

抗Xa因子活性测定评价依诺肝素在心导管室中应用的安全性和有效性

目的　低分子量肝素可以有效的取代普通肝素应用于急性冠状动脉综合征 (ACS)的治疗。然而 ,ACS患者在行心导管检查时最佳的抗凝策略尚不明了。本研究旨在用抗Xa因子活性检测评价低分子量肝素在心导管室中应用的安全性和有效性 ,探索适合国人的心导管检查及经皮冠状动脉介入治疗 (PCI)的抗凝策略。方法　共入选ACS患者 1 76例。在每 1 2h(7:0 0 1 9:0 0 )皮下注射依诺肝素 1mg kg至少 48h后 ,不追加普通肝素或低分子量肝素于心导管室行冠状动脉造影 ,不进行凝血系统监测。 60例 (34 1 % )患者继之行PCI。结果　在心导管检查前的肝素抗Xa因子活性是 (0 81±0 2 7)IU ml,93 2 %的患者抗Xa因子活性 >0 50IU ml,且抗Xa因子活性与从注射到开始导管检查的时间无关 (P =0 0 97)。PCI组术后 30d无死亡、急性冠状动脉再闭塞或急诊血管重建事件。 3例(5 0 % )PCI患者术中出现血栓和 (或 )栓塞事件。单纯冠状动脉造影组有 1例因三支血管病变在术后1 7d等待冠状动脉旁路移植术时发生急性心肌梗死而行急诊PCI;另 1例患者在冠状动脉造影后 2 1d死于十二指肠穿孔。 1 76例入选患者无一例出现严重出血事件 ;PCI组有 3例 (5 0 % )患者出现轻度穿刺部位出血 ,单纯冠状动脉造影组为 5例 (4 3 % )。结论　本研究初步表明     

The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion: assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study.

AIMS: To compare the feasibility and safety of transoesophageal echocardiograpy-guided cardioversion (CV) with enoxaparin and unfractionated heparin (UFH) in patients with atrial fibrillation (AF). METHODS AND RESULTS: The Assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II pilot trial compared the safety and efficacy of enoxaparin with UFH in 155 patients with AF who were scheduled for transoesophageal echocardiography (TEE)-guided CV. Safety outcomes over a 5-week period were ischaemic stroke, major or minor bleeding, and death. Efficacy outcomes were length of stay (LOS) and return to normal sinus rhythm (NSR). Of the 76 patients assigned to the enoxaparin group, 72 (94.7%) had a transoesophageal echocardiogram and 63 (82.9%) had early CV, of which 59 (93.7%) were successful. Of the 79 UFH patients, 66 (83.5%) had a transoesophageal echocardiogram and 58 (73.4%) had early CV, of which 54 (98.2%) were successful. There were no significant differences in embolic events, bleeding, or deaths between groups. The enoxaparin group had shorter median LOS compared with the UFH group [3(2-4) vs. 4(3-5)] days; P<0.0001). There was also more NSR at 5 weeks in the enoxaparin group (76 vs. 57%; P=0.013). CONCLUSION: In the ACUTE II trial, there were no differences in safety outcomes between the two strategies. However, the enoxaparin group had a shorter LOS. Thus, the TEE-guided enoxaparin strategy may be considered a safe and effective alternative strategy for AF. The shorter LOS may translate to lower costs using the enoxaparin TEE-guided approach.     

利伐沙班治疗非ST段抬高急性冠脉综合征的疗效观察

目的:通过前瞻性随机对比研究,比较利伐沙班和伊诺肝素用于非ST段抬高急性冠脉综合征治疗的有效性及安全性。方法:入选符合本研究标准的79例非ST段抬高急性冠脉综合征患者,随机分为两组,利伐沙班组38例,利伐沙班5mg/12h口服;伊诺肝素组41例,1mg/(kg·12h)皮下注射。疗程8d。结果:住院期间利伐沙班组发生心脏不良事件8例,出血4例;伊诺肝素组发生心脏不良事件10例,出血7例。随访期间利伐沙班组发生心脏不良事件14例;伊诺肝素组发生心脏不良事件15例。两组间心脏不良事件发生率及出血发生率均无统计学差异(P>0.05)。结论:利伐沙班与伊诺肝素抗凝治疗效果相当,出血的发生率相似,该药既有效又安全。     

依诺肝素钠原料药细菌内毒素检查方法的研究

目的建立依诺肝素钠原料药的细菌内毒素检查方法。方法按照《中国药典》2010年版二部,确定合理的依诺肝素钠细菌内毒素限值,并研究依诺肝素钠对细菌内毒素与鲎试剂反应的干扰情况,以确定其不干扰试验浓度。结果确定依诺肝素钠的细菌内毒素限值为0．01EU／U,使用2个厂家生产的鲎试剂试验,本品配制成3U／mL浓度对反应均无干扰作用。结论细菌内毒素检查法可用于依诺肝素钠细菌内毒素的检查。     

Haemorrhagic Effect of Enoxaparin,a Low Molecular Weight Heparin: Comparison with Unfractionated Heparin in Humans

The haemorrhagic effects of unfractionated heparin (UFH) and the low molecular weight heparin (LMWH) enoxaparin were investigated and compared in the gastric mucosa (haemorrhage induced by biopsy) and skin (haemorrhage induced by Simplate) of 12 healthy volunteers. Administration of UFH and LMWH (given in a dose of 75 anti-Xa U/kg intravenously) increased median gastric bleeding time (3.5 min) and geometric mean blood loss (11.5 l) to 19 min (p = 0.00003) and 54.1 l (p = 0.0021) after UFH and to 13 min (p = 0.008) and 29.0 l (p = 0.275) after LMWH. Median skin bleeding time (4.25 min) increased to 6.0 min after UFH (p = 0.003) and to 6.75 min after LMWH (p = 0.0008). Mean heparin activity in plasma was 20% higher after LMWH than after UFH. The calculated gastric bleeding time to heparin activity ratio was significantly lower for LMWH than for UFH (0.05).     

Additional clinical benefit of enoxaparin in COPD patients receiving salmeterol and fluticasone propionate in combination

It is now well recognised that heparin possesses numerous anti-inflammatory properties in addition to its anticoagulant properties. Thus, the aim of this study was to investigate the effects of the low molecular weight heparin, enoxaparin (ENX), as an add-on therapy for a period of 12 weeks, to inhaled salmeterol/fluticasone propionate (SLM/FP) combination in patients with stable chronic obstructive pulmonary disease (COPD). Forty-six patients were randomised to receive 12 weeks of treatment in one of two treatment groups: (1) fixed combination of SLM 50 microg and FP 500 microg Diskus, one inhalation twice daily; or (2) as group 1 plus 20 mg ENX administered subcutaneously once daily for 12 weeks. Patients attended the clinic before and after 4, 8 and 12 weeks of treatment for evaluations of lung function, blood gas tensions, dyspnoea and supplemental salbutamol use. Thirty-six patients completed the 12-week treatment period, 20 from group 1 and 16 from group 2. A significant increase in forced expiratory volume in 1 s (FEV1) over baseline was observed after 12 weeks of treatment in group 1 (0.145 L, 95% CI: 0.994-1.406, p<0.01), whilst significant increases in FEV1 over baseline were observed in group 2 after 4, 8 and 12 weeks of treatment with a maximum increase at 12 weeks of 0.244 L (95% CI: 1.175-1.596, p<0.01). Both treatment groups experienced similar improvements in blood gas tensions, dyspnoea and supplemental salbutamol use. Our results suggest that addition of ENX to conventional therapy of COPD may provide additional clinical benefit and must be further investigated as a treatment for COPD.     

冠心病介入治疗中应用低分子肝素与普通肝素的随机对照研究

目的探讨冠心病患者经皮冠状动脉介入治疗（PCI）中应用低分子肝素（LMWH）替代普通肝素（UFH）的安全性和有效性。方法自2003年10月至2005年2月共入选966例申请一次性行PCI的患者,所有患者均签署了知情同意书。966例患者中最终完成PCI治疗者455例[包括283例为非ST段抬高急性冠脉综合征（ACS）者]。未接受PCI治疗者511例。研究采用随机对照方法,将入选患者分为LMWH组和静脉UFH组,LMWH组484例,静脉UFH组482例。LMWH组采用依诺肝素（enoxaparin）,按1mg／kg的剂量于PCI手术前至少给予2次皮下注射（每12h一次）,PCI手术在最后1次皮下注射30min后开始。完成冠状动脉造影或PCI后,立即拔出鞘管。静脉UFH组的患者于手术前即刻先给予普通肝素25rIlg静脉推注,如果造影显示适合PCI时,再追加65mg。完成PCI后4h左右拔出鞘管。LMWH组和静脉UFH组中最终行PCI者各为227例和228例。结果（1）LMWH组中1例于PCI术中发生急性血栓形成致急性心肌梗死（AMI）,PCI术后及住院期间未见急性和亚急性血栓形成。静脉UFH组术中和住院期间无急性和亚急性血栓形成。住院期间心脏事件发生率（死亡、AMI和再次血管重建）在LMWH组为0．44％,静脉UFH组为0;（2）LMWH组均于术后即刻拔出鞘管,穿刺局部发生血肿8例,静脉UFH组于术后4h左右拔出鞘管,穿刺局部发生血肿20例,前者血肿发生率明显低于后者,差异有统计学意义（P〈0．05）;（3）随访1个月LMWH组心脏事件发生率为0,静脉UFH组1例于院外发生亚急性血栓致AMI,再次行PCI成功,随访期间心脏事件发生率为0．43％。结论本研究结果提示对于拟行PCI的冠心病患者或非sT段抬高ACS患者术前给予至少2次依诺肝素皮下注射（1mg／kg,每12h一次）,并于最后1次皮下注射的8h内行PCI是安全和有效的,术前和术中不需要给予静脉UFH,术后可即刻拔出鞘管。