缺血性脑卒中二级预防治疗的依从性研究

目的采取有效措施减少缺血性脑卒中再发,对缺血性脑卒中或短暂性脑缺血发作(TIA)患者采取ABCDE策略,观察患者出院后1年能否维持高水平药物治疗符合率。方法选择缺血性脑卒中或TIA患者178例,采取ABcDE策略进行规范的二级预防。观察患者出院时及出院后1年二级预防中抗血小板、降压、降糖和他汀类药物治疗的符合率。结果 178例患者中既往有缺血性脑卒中或TIA史126例,其住院前抗血小板治疗比例为41.3%,服用降压、降糖和他汀类药物治疗比例分别为89.9%、83.3%和13.5%;155例完成出院1年随访,降压治疗符合率为100%,抗血小板治疗符合率为97.2%,降糖和他汀类药物治疗符合率为98.2%和84.3%。结论采取ABCDE策略对缺血性脑卒中或TIA患者进行规范干预后,明显缩小二级预防循证证据与临床实践之间的差距,患者出院1年药物治疗符合率维持在较高水平。     

卒中专病门诊贯彻卒中二级预防指南的研究

目的观察医师培训和专病门诊对缩小临床实践与缺血性卒中二级预防指南差距的影响。方法选择在卒中专病门诊就诊的305例缺血性卒中患者,比较其在医师规范培训前后及出院与在专病门诊随访期间抗栓药、他汀类药物、不规范用药和降压药的使用情况。结果医师经培训后提高了二级预防用药的规范性,患者出院的抗栓药（79．3％比93．1％,P〈0．01）和他汀类药（19．5％对59．2％,P〈0．01）使用率显著提高,不规范用药（47．1％比27．5％,P=0．001）显著降低。高血压的治疗率（88．4％比94．0％）差异无统计学意义。与出院时相比,专病门诊随访患者的抗栓药和他汀类药使用率进一步提高,不规范用药进一步降低。出院带药规范者随访期的用药依从性高。结论医师培训能提高缺血性卒中二级预防处方的规范性,专病门诊能进一步提高患者出院带药及随访期用药的依从性。     

Antiplatelet therapy in secondary stroke prevention

This article focuses on recent data about the safety and effectiveness of antiplatelet therapies for secondary stroke prevention. Highlights include a discussion of changes in the professional labeling for aspirin and the results of a low- versus high-dose aspirin trial (Aspirin after Carotid Endarterectomy trial). Safety issues regarding aspirin also are considered. Other topics include a review of recent data on thrombotic thrombocytopenic purpura (TTP) associated with ticlopidine and a brief update on clopidogrel. A summary of discussions related to the European Stroke Prevention Study 2 data and Food and Drug Administration consideration of combination dipyridamole/aspirin therapy are presented.     

Antithrombotic secondary prevention after stroke

Opinion statement In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura [TTP]), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.     

北京地区缺血性脑卒中或短暂性脑缺血发作二级预防的研究

目的对入院的缺血性脑卒中或短暂性脑缺血发作(TIA)患者采取ABCDE策略治疗,分析患者出院后能否维持高水平药物治疗的符合率。方法选择2007年8～12月连续收入北京地区21家医院神经内科病房的缺血性脑卒中和(或)TIA患者1166例,记录患者二级预防中抗血小板、降压、降糖及调脂药物等治疗情况,出院后对患者进行随访,分析出院后90d、6个月和1年二级预防中抗血小板、降压、降糖和调脂治疗的符合率。结果 1166例患者中,复发性脑卒中541例,其抗血小板治疗比例为58.4%,降压、降糖和他汀类药物治疗比例分别为82.3%、85.3%和14.2%。出院后,完成90d、6个月及1年随访的患者分别为1012例、1012例和981例,其二级预防中抗血小板、降压、降糖和调脂治疗的符合率维持在较高水平。结论复发性脑卒中二级预防现状不容乐观,采取ABCDE策略治疗,对入院的缺血性脑卒中或TIA患者进行规范干预后,明显缩小二级预防循证证据与临床实践的差距,患者出院后,二级预防治疗的符合率维持在较高水平。     

糖尿病与卒中二级预防

糖尿病是脑卒中的重要危险因素。对糖尿病患者进行积极降糖治疗,对于卒中一级预防有重要意义。糖尿病是卒中复发的独立危险因素,其在不同亚型卒中复发中的作用是不同的。强化降糖治疗在卒中二级预防中的作用尚未明确。     

Understanding the PRoFESS study for secondary stroke prevention

Opinion statement  The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is the largest secondary stroke prevention study completed to date. It compared extended-release dipyridamole plus aspirin (eDYP-ASA) versus clopidogrel and telmisartan versus antihypertensive regimens excluding angiotensin receptor blockers (ARBs). No statistical differences were found in either arm for the primary outcome of fatal or nonfatal stroke or prespecified secondary end points. eDYP-ASA also was associated with increases in major hemorrhagic events but not with statistical increases in combined rates of stroke recurrence or hemorrhage. Despite PRoFESS, the role of ARBs post stroke remains unclear, as concomitant angiotensin-converting enzyme inhibitor use in PRoFESS obscured whether just blood pressure lowering or renin-angiotensin system blockade is important. The resulting interpretation that eDYP-ASA is “not noninferior” has raised questions about how to interpret noninferiority analyses. Also, although the PRoFESS editorialists suggested that aspirin, the historical bystander control, was the “winner,” a review of prior antiplatelet studies suggests that the benefits of aspirin, either as combination or monotherapy, are outweighed by its bleeding hazards. The benefits of clopidogrel or eDYP-ASA, compared with aspirin, are small but real, and both remain preferred agents in secondary stroke prevention.     

Antiplatelet agents for secondary prevention of stroke

Patients with recent ischemic stroke or transient ischemic attack (TIA) face a high risk of recurrent stroke as well as an increased risk of myocardial infarction and sudden cardiac death. In the absence of a clearly established indication for long-term anticoagulation, such as atrial fibrillation, antiplatelet agents are the antithrombotic drugs of choice for preventing recurrent vascular events. For many years, aspirin (ASA) has been the first-line therapy for patients at high risk of vascular ischemic events. Two large clinical trials have established the superiority of the combination of ASA and extended-release dipyridamole (ASA/ERDP) over ASA alone in patients with recent noncardioembolic ischemic stroke or TIA. Clopidogrel, another antiplatelet agent, is a reasonable alternative to ASA, but its superiority to ASA in patients with a history of stroke has not been as clearly established. The combination of ASA and clopidogrel, which is effective in patients with acute coronary syndrome, has not been shown to be either effective or safe, compared with either agent alone, in stroke patients, although there may be some benefit to this combination in patients with acute TIA. The results from a large randomized trial comparing ASA/ERDP with clopidogrel, anticipated soon, will further assist clinicians in choosing among available antiplatelet agents.     

Medical therapy for secondary prevention of stroke

The identification and modification of risk factors for stroke and their appropriate management can lead to reduction of stroke incidence. The real impact on recurrences of risk factors associated with lifestyles has not been thoroughly investigated, and the possible role of their modification in secondary prevention is principally extrapolated from primary prevention studies. On the other hand, several pathological conditions such as hypertension, atrial fibrillation, carotid stenosis, and diabetes are known to favour the risk of recurrence. Available antiplatelet regimens offer only partial protection against stroke and more efficacious antithrombotic agents would be useful. There is no doubt that warfarin is effective in preventing recurrence in stroke patients with atrial fibrillation. However, a careful etiological subtyping of stroke is recommended before starting treatment.     

Antithrombotic drugs for the secondary prevention of ischemic stroke

On the assumption that antithrombotic drugs are able to reduce the incidence of any vascular event independently of where it first occurs, they are used for the secondary prevention of arterial vascular disease in different locations. The Antiplatelet Trialists' Collaboration meta-analysis has shown that the net benefit of antiplatelet drugs in the prevention of stroke, acute myocardial infarction and vascular death is about the same for patients with prior stroke or prior myocardial infarction. Most of the trials included in the Antiplatelet Trialists' Collaboration meta-analysis used aspirin, which was shown to lower the risk of stroke, myocardial infarction, and vascular death in patients with a history of transient ischemic attack or stroke. Aspirin should be given to patients operated on for symptomatic carotid stenosis and should be considered for asymptomatic patients. In a comparative study ticlopidine (500 mg) vs aspirin (650 mg), ticlopidine reduced the relative risk of vascular events by 9% and of recurrent stroke by 21%. When clopidogrel (75 mg) was compared with aspirin (325 mg), a 7.3% relative risk reduction was seen in the stroke group (6431 patients) of the CAPRIE study; a reduction in hemorrhagic events, especially in gastrointestinal bleeding, was also seen. At variance with previous studies, the ESPS-2 showed an advantage when dipyridamole (400 mg) was added to aspirin (50 mg). Oral anticoagulants are more effective than aspirin in the prevention of cardioembolic stroke in patients with atrial fibrillation. The higher efficacy of indobufen with respect to aspirin in this particular setting needs confirmation. Inhibition of thrombosis may be one of the mechanisms explaining the effect of statins in reducing both stroke and cardiac events in high-risk patients.     

Warfarin versus aspirin in the secondary prevention of stroke: The WARSS study

The role of anticoagulation in the secondary prevention of noncardioembolic stroke has long been an area of debate. Previous evidence has shown that anticoagulation is unsafe at an International Normalized Ratio between 3.0 and 4.5. Results of the recently published Warfarin-Aspirin Recurrent Stroke Study (WARSS) suggest that there is no difference between warfarin and aspirin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Differences in the therapeutic interventions used may have had an effect on the differences in endpoints achieved as compared with previous studies. Results of ongoing trials are anticipated to further clarify the role of anticoagulation in the secondary prevention of stroke.     

缺血性脑卒中二级预防他汀类药物应用状况调查

目的了解缺血性脑卒中患者他汀类药物使用情况,分析影响他汀类药物使用的因素。方法从2014年1~12月连续收住我院神经内科住院的740例缺血性脑卒中患者中,选择360例复发性脑卒中患者,根据患者是否应用他汀类药物分为治疗组131例,未治疗组229例。按LDL-C2.6mmol/L的标准为治疗达标,调查340例患者入院时他汀类药物应用情况,并对相关的危险因素进行logistic回归分析。结果 360例患者中,服用他汀类药物131例,药物治疗率36.4%,未用他汀类药物229例,占63.6%。治疗组与未治疗组年龄≥65岁(58.8%vs47.2%)、高脂血症(30.5%vs 19.2%)、冠心病(32.1%vs 8.3%)和2型糖尿病(55.7%vs 30.1%)比较,差异有统计学意义(P0.05,P0.01)。未服用他汀类药物的原因中,患者自行停药及病情好转停药63.3%,医师未建议服用22.7%,存在药物不良反应5.2%。LDL-C达标患者104例,达标率为28.9%。进一步logistic回归分析显示,年龄≥65岁、冠心病、高脂血症、抗血小板药物、降糖药物是影响患者他汀药物治疗的独立危险因素(P0.05,P0.01)。结论缺血性脑卒中患者他汀类药物治疗率低,LDL-C达标率更低,应加强患者教育及临床医师培训,提高患者服用他汀类药物的依从性。