Warfarin and aspirin versus aspirin alone in patients with acute myocardial infarction: a pilot study

The benefits of anticoagulant therapy and antiplatelet agents in secondary prevention of myocardial infarction (MI) are well known. Administration of combined warfarin and aspirin (ASA) has not been well studied. The objective of this study was to compare the effect of coadministration of warfarin and ASA with administration of ASA alone on outcome of patients after MI. One hundred forty age- and sex-matched survivors of MI were randomized to receive either 100 mg/day ASA plus enough warfarin to reach a target: international normalized ratio of 2.5 (range: 2-3) (group A, n = 70), or only 100 mg/day ASA (group B, n = 70). The patients were examined for several variables including development of hemorrhage, reinfarction, and rehospitalization for 1 year post MI. Of the variables studied, minor hemorrhagic episodes were observed significantly (p = 0.002) more in group A than in group B patients. Rehospitalization and reinfarction rates, although occurring with lower frequencies in group A than in group B, did not reach the statistical significance level. In postmyocardial infarction patients, warfarin plus ASA did not provide a clinical benefit beyond that achievable with aspirin monotherapy, and for the observed markedly higher incidence of minor hemorrhage in combination therapy, antiplatelet therapy alone seems to be a more reasonable approach.     

华法林与阿司匹林预防非瓣膜性心房颤动患者血栓栓塞的随机对照研究

目的通过前瞻性、随机、多中心研究比较阿司匹林与调整剂量华法林预防非瓣膜性心房颤动(房颤)患者发生血栓栓塞的有效性和安全性。方法在18个中心,根据入选标准将非瓣膜性房颤患者随机分配至阿司匹林组(150~160mg/d)和调整剂量华法林组(初始剂量2mg/d),目标国际标准化比值(INR)为2·0~3·0(年龄≥75岁者的INR为1·6~2·5)。常规门诊随访,调整华法林剂量并记录两组患者的终点事件和不良反应发生情况。主要终点事件为缺血性脑卒中和死亡,次要终点事件包括短暂性脑缺血发作、腔隙性脑梗死、外周动脉栓塞、急性心肌梗死和严重出血。结果共704例患者进入分析,阿司匹林组369例,华法林组335例。男性420例(59·7%),平均年龄(63·3±9·9)岁,两组患者基线特征(包括合并疾病和伴随用药)差异无统计学意义。随访时间中位数19个月(2~24个月)。与阿司匹林比较,调整剂量华法林明显降低主要终点事件发生率[2·7%比6·0%,P=0·03,OR0·44,95%可信区间(CI)为0·198~0·960],相对危险下降54%;缺血性脑卒中的相对危险下降62%(1·8%比4·6%,P=0·04,OR0·38,95%CI为0·147~0·977);总血栓栓塞事件相对危险下降52%(10·6%比5·4%,P=0·01,OR0·48,95%CI为0·269~0·858)。次要终点事件两组间差异无统计学意义。华法林组轻微出血和严重出血发生率均高于阿司匹林组(P<0·05)。华法林组总死亡率低于阿司匹林组[4例(1·2%)比8例(2·2%)],但差异无统计学意义(P>0·05);包括主要和次要终点的联合终点事件华法林组低于阿司匹林组(8·4%比13·0%,P=0·047)。结论与阿司匹林相比,华法林可明显降低国人非瓣膜性房颤患者脑卒中的发生率,华法林组出血的发生率高于阿司匹林组,但多数出血并发症发生在INR>3·0。严密监测(INR2·0~3·0)下的调整剂量华法林安全有效。     

Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study.

AIM: To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI). METHODS: Patients who were hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed according to the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow-up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently withdrawn as opposed to 14.0% in the aspirin group (P<0.0001). Analyses were performed on an intention-to-treat basis. RESULTS: The combination of cardiovascular death, reinfarction or stroke was registered in 28.1% in the aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin group (NS). Whereas no difference was found with regard to total mortality or reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006). CONCLUSION: A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding.     

Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation.

BACKGROUND: Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients. METHODS: In the Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation (AFASAK 2) Study, we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; aspirin, 300 mg/d; or adjusted-dose warfarin therapy aiming at an international normalized ratio of the prothrombin time ratio (INR) of 2.0 to 3.0. The study was scheduled for 6 years from May 1, 1993, but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2, 1996. Minor and major bleeding events were recorded prospectively. The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model. RESULTS: Of 677 included patients, 130 (median age, 77 years; range, 67-89 years) experienced bleeding. One woman and 12 men experienced major bleeding. Four had intracranial bleeding: 2 cases were fatal and 2 were nonfatal. During treatment with mini-dose warfarin, warfarin plus aspirin, aspirin, and adjusted-dose warfarin, the annual rate of major bleeding was 0.8%, 0.3%, 1.4%, and 1.1%, respectively (P = .20). After 3 years of treatment the cumulative rate of any bleeding was 24.7%, 24.4%, 30.0%, and 41.1% (P = .003), respectively. Increasing INRvalue (P<.001) and prior myocardial infarction (P = .001) were independent risk factors for bleeding, whereas increasing age was not. CONCLUSIONS: Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding. The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy (INR, 2.0-3.0).     

Low-dose aspirin therapy for chronic stable angina. A randomized, placebo-controlled clinical trial

OBJECTIVE: To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infarction among patients with chronic stable angina. DESIGN: A randomized, double-blind, trial. PATIENTS: The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infarction, stroke, or transient ischemic attack who were enrolled in the Physicians' Health Study, a trial of aspirin among 22,071 male physicians. INTERVENTION: Patients were randomly assigned to receive alternate-day aspirin therapy (325 mg) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infarction, stroke, or cardiovascular death. RESULTS: During follow-up, 27 patients had confirmed myocardial infarctions; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo (relative risk, 0.30; 95% CI, 0.14 to 0.63; P = 0.003). While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model, an overall 87% risk reduction was calculated (relative risk, 0.13; CI, 0.04 to 0.42; P less than 0.001). For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty, an almost identical reduction in the risk for myocardial infarction was found (relative risk, 0.14; CI, 0.04 to 0.56; P = 0.006). Of 13 strokes, 11 occurred in the aspirin group and 2 in the placebo group (relative risk, 5.4; CI, 1.3 to 22.1; P = 0.02). No stroke was fatal, but 4 produced some long-term impairment of function. One stroke, in the aspirin group, was hemorrhagic. CONCLUSION: Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infarction among patients with chronic stable angina, a group of patients at high risk for cardiovascular death (P less than 0.001). Although our results for stroke were based on small numbers, they suggested an apparent increase in frequency of stroke with aspirin therapy; this finding requires confirmation in randomized trials of adequate sample size.     

Antithrombotic treatment and the incidence of angina pectoris

BACKGROUND: In primary prevention, anticoagulation with warfarin sodium to an international normalized ratio of 1.5 and 75 mg of aspirin per day each reduced the incidence of coronary heart disease (CHD). Effects on the development of angina pectoris and total CHD (resulting from angina, myocardial infarction, and coronary death) have been assessed, particularly in light of recent evidence that warfarin may have a "durable effect" on CHD through effects on the pathologic condition of the vessel walls involved. METHODS: The Thrombosis Prevention Trial was carried out in 5499 men aged 45 through 69 years who were at increased risk of CHD. The trial was factorial, with 1 group taking active warfarin and active aspirin, 1 taking active warfarin and placebo aspirin, 1 taking placebo warfarin and active aspirin, and 1 taking double placebo treatment. In addition to those with myocardial infarction and coronary death, men developing angina pectoris after entry to the trial were identified. RESULTS: Warfarin appeared to reduce the incidence of stable angina by 16% (95% confidence interval [CI], -14 to 38), although not significantly (P =.26), while aspirin increased the incidence by 39% (95% CI, 0 to 91) (P =.05). The incidence of stable angina was 37% (95% CI, -1 to 60) less in those taking warfarin than in those taking aspirin (P =.05). Warfarin reduced total CHD by 18% (95% CI, 4 to 30) (P =.01), while the reduction due to aspirin was 8% (95% CI, -10 to 22) (P =.36). CONCLUSIONS: The results are compatible with the concept of a durable effect of warfarin on the chronic pathologic conditions underlying angina, although this has not been established with certainty. Further research is needed to confirm or refute our findings, because they carry potentially important implications for the primary prevention of CHD with the use of antithrombotic agents.     

Superiority of warfarin over aspirin long term after thrombolytic therapy for acute myocardial infarction

Results of recent clinical trials have unequivocally established the value of intravenous thrombolytic therapy in enhancing survival after acute myocardial infarction. However, the optimum long-term antithrombolytic strategy for prevention of recurrent cardiac complications after thrombolysis is unknown at the current time. To determine whether aspirin or warfarin best prevents postdischarge recurrent cardiac events (unstable angina, reinfarction, pulmonary edema, or/and death), we analyzed the long-term course of 203 patients at our institution who received intravenous thrombolytic therapy (streptokinase, tissue plasminogen activator, or urokinase) for acute myocardial infarction. Of these, 129 (64%) survived to hospital discharge without revascularization--92 patients (71%) received aspirin (325 mg/day). whereas 37 (29%) received warfarin. The choice of drug was made by the treating physician. By a mean of 2.5 years of follow-up, 34 of 92 patients receiving aspirin (37%) versus 6 or 37 receiving warfarin (16%) (p less than or equal to 0.02) had unstable angina, reinfarction, pulmonary edema, and/or death. No life-threatening hemorrhage occurred in either group. Warfarin appears to be superior to aspirin long term in patients with postlysis myocardial infarction for the prevention of recurrent cardiac complications.     

Echocardiographic determination of left atrial function and its application for assessment of mitral flow velocity pattern

Forty-three patients presenting with unstable angina or myocardial infarction were randomised double blind to warfarin [target international normalised ratio (INR), 2.0 to 2.5] and aspirin (150 mg) daily or placebo plus aspirin (150 mg) daily. Coronary flow was assessed with the thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC). Coronary artery flow was reduced (higher CTFC) at baseline in culprit arteries (mean +/-SD, 37.1+/-15.4 frames) compared to nonculprit arteries (22.5+/-6.7 frames, P<0.0001). In patients with a patent artery at follow-up, coronary flow was unchanged after ten weeks of warfarin and aspirin (-2.0+/-19.9 frames) or aspirin alone (3.8+/-10.4 frames, P = 0.20). Patients randomised to aspirin alone were more likely to progress to total occlusion [aspirin, 7 of 19 (37%) vs. warfarin and aspirin, 1 of 24 (4%); P = 0.01). Higher baseline culprit artery CTFC was also associated with an increased risk of late occlusion [+10 frames; odds ratio (OR), 1.65; 95% CI, 1.01 to 2.33]. Coronary flow remained impaired ten weeks after presentation with myocardial infarction or unstable angina. Combination warfarin and aspirin therapy did not improve flow in vessels that remained patent but did reduce the risk of progression to occlusion.     

Efficacy and safety of aspirin,clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS₂ score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02–59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan–Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.     

高龄持续性心房纤颤患者不同剂量阿司匹林与华法林抗栓疗效及安全性比较

目的观察在持续性心房纤颤（房颤）的高龄患者中,不同剂量阿司匹林及华法林的疗效和安全性。方法选取年龄≥75岁的持续性房颤患者217例,分为4组,华法林高抗凝组『2．0〈国际标准化比率（international normalized ratio,INR）≤3．0154例,华法林低抗凝组（1．6≤INR≤2．0）53例,阿司匹林组（325mg／d）47例,阿司匹林组（200mg／d）63例,观察各组中血栓栓塞和出血事件的发生率。结果华法林高抗凝组与低抗凝组血栓栓塞发生率明显低于阿司匹林组（325mg／d）,差异有统计学意义（矿=6．487,P=O．011;矿=7．929,P=O．005;r=6．354,P=O．012;r=7．771,P=O．005）;华法林高抗凝组出血发生率明显高于低抗凝组和阿司匹林组（200mg／d）,差异有统计学意义（14.8％＇US．0m0,P〈0．05）;华法林高抗凝组与阿司匹林组（325mg／d）出血发生率比较,差异无统计学意义（P〉O．05）。结论对于年龄≥75岁的老年持续性房颤患者,低抗凝强度华法林（1．6≤INR≤2．0）安全有效,其疗效优于阿司匹林。     

Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group)

In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination antithrombotic therapy with antiplatelet agents and anticoagulants for patients with atherosclerotic heart disease

We reviewed the efficacy and safety of combination antithrombotic therapy with aspirin plus warfarin versus aspirin alone in patients with atherosclerotic heart disease. We performed a comprehensive MEDLINE search of English-language reports published between 1966 and 2002 and search of references and relevant papers. Only clinical research studies on primary or secondary prevention of cardiovascular events in patients at high risk for coronary artery disease or patients experiencing unstable angina or myocardial infarction were included. Despite daily aspirin treatment, many patients break through aspirin treatment and experience cardiovascular events. Individuals at high risk for coronary disease or with established disease benefit from combination therapy with aspirin plus warfarin, if compliance with warfarin is greater than 70% and the target international normalized ratio (INR) of 2.0-2.5 is achieved. Combination therapy within these parameters leads to a 29-45% reduction in the risk of death, reinfarction and/or ischemic stroke. There is a significant increase in the rate of minor and a slight increase in the rate of major bleeding with combination therapy. Other potential indications for combination therapy include myocardial infarction associated with acute left ventricular aneurysm or significant left ventricular systolic dysfunction. In spite of reluctance to use oral anticoagulants, several large, randomized clinical trials support combination therapy with aspirin plus warfarin (INR, 2.0-2.5) in high-risk patients with atherosclerotic heart disease. Combination therapy increases the risk of minor and major bleeding, but not intracranial bleeding.     

Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting.

AIM: The aim of this study was to evaluate the antithrombotic treatment adopted after coronary stenting in patients requiring long-term anticoagulation. METHODS AND RESULTS: We analysed retrospectively all consecutive patients on warfarin therapy (n = 239, mean age 70 years, men 74%) who underwent percutaneous coronary intervention (PCI) in 2003-04 in six hospitals. An age- and sex-matched control group with similar disease presentation (unstable or stable symptoms) was selected from the study period. Primary endpoint was defined as the occurrence of death, myocardial infarction, target vessel revascularization, or stent thrombosis at 12 months. Warfarin treatment was an independent predictor of both primary endpoint (OR 1.7, 95% CI 1.0-3.0, P = 0.05) and major bleeding (OR 3.4, 95% CI 1.2-9.3, P = 0.02). Triple therapy with aspirin and clopidogrel was the most common (48%) option in stented patients in warfarin group, and there was a significant (P = 0.004) difference between the drug combinations in stent thrombosis with the highest (15.2%) incidence in patients receiving warfarin plus aspirin combination. CONCLUSION: Our study shows that the prognosis is unsatisfactory in warfarin-treated patients irrespective of the drug combination used. Aspirin plus warfarin combination seems to be inadequate to prevent stent thrombosis.     

Progression of the Culprit Lesion in Unstable Coronary Artery Disease With Warfarin and Aspirin Versus Aspirin Alone: Preliminary Study

Objectives. This study assessed whether combination therapy with aspirin and warfarin for 10 weeks reduces the risk of progression or reocclusion of the unstable coronary artery lesion.Background. Reocclusion of the culprit coronary artery occurs in up to one third of patients during the 3 months after myocardial infarction (MI) or unstable angina and is associated with increased morbidity and mortality.Methods. Fifty-seven patients presenting with unstable angina or MI who had an identifiable culprit lesion at coronary angiography were randomized in double-blind manner to receive warfarin (target international normalized ratio [INR] 2.0 to 2.5) or placebo in addition to aspirin (150 mg daily). Changes in the culprit lesion were assessed by quantitative angiography in 50 patients after 10 weeks of therapy or after a clinical event. Progression of the culprit lesion was defined as a decrease in minimal lumen diameter >0.4 mm or a new total occlusion. Regression was defined as an increase in minimal lumen diameter >0.4 mm.Results. In subjects randomized to receive warfarin, the culprit lesion was less likely to progress (1 [4%] vs. 8 [33%]) and more likely to regress (5[19%] vs. 2[9%]) than in subjects receiving placebo (p = 0.02). Recurrent MI or a new occlusion at angiography occurred in 2 (7%) of 29 patients receiving warfarin versus 11 (39%) of 28 patients receiving placebo (p = 0.005).Conclusions. In patients with an acute coronary syndrome, combined therapy with aspirin and warfarin with a target INR of 2.0 to 2.5 for 10 weeks reduces the risk of progression or reocclusion of the culprit coronary lesion.     

Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?

AIMS: To identify factors associated with the use of single or dual antiplatelet therapy in patients prescribed warfarin following coronary stenting and to investigate whether single (aspirin or thienopyridine) vs. dual antiplatelet therapy plus warfarin leads to an excess of adverse outcomes. METHODS AND RESULTS: We analysed data from 800 patients with an acute coronary syndrome who underwent coronary stenting (130 patients received a drug-eluting stent) and were discharged on warfarin and either dual (n = 580) or single (n = 220) antiplatelet therapy. The use of single antiplatelet therapy was more common in Europe than in the USA (34 vs. 17%, P < 0.001). There was no difference in major bleeding in hospital or in 6-month mortality or myocardial infarction. In the single antiplatelet group, the use of either aspirin or thienopyridine (clopidogrel or ticlopidine) in combination with warfarin resulted in similar outcomes. CONCLUSION: Use of single vs. dual antiplatelet therapy and warfarin following stenting is common. In this observational study, there was no difference in mortality or myocardial infarction at 6 months; however, larger trials are needed to assert any firm recommendations.     

华法林预防心房颤动患者发生脑梗塞的临床意义

目的:通过比较华法林与拜阿司匹林对非瓣膜性心房颤动(NVAF)的疗效及安全性,以明确NVAF患者抗栓治疗的最佳选择。方法:根据国际指南中关于NVAF血栓栓塞危险因素的建议,入选120例NVAF患者,随机均分为华法林组(目标INR 2～3)与阿司匹林(100mg/d)组,比较两组脑梗塞和出血事件的发生率。结果:华法林组脑梗塞发生率明显低于阿司匹林组(1.67%比8.33%,P<0.05)。华法林组7例(11.67%),阿司匹林组6例(10.00%)发生出血,华法林组出血发生率高于阿司匹林组,但差异无显著性(P>0.05),两组均无严重岀血情况。结论:华法林抗凝效果明显,可以安全、有效地减少和防止脑梗塞发生。     

华法林与阿司匹林和氯吡格雷三重抗栓治疗的安全性

目的观察有华法林抗栓指征的患者,冠状动脉(简称冠脉)支架植入术后,联合华法林、阿司匹林和氯吡格雷三重抗栓治疗的安全性。方法选择23例心房颤动(有1项以上危险因素)、机械瓣置换术后和左室血栓的患者,冠脉植入药物洗脱支架后,联合华法林、阿司匹林和氯吡格雷(三重抗栓组)治疗,严格控制国际标准化比值(INR)1.6～2.5,观察1年总的和严重出血事件的发生率。分别选择同期86例冠心病患者,植入冠脉支架后应用阿司匹林和氯吡格雷(双重抗血小板组)治疗,64例有华法林抗凝指征的患者,应用华法林抗凝(抗凝组)治疗(INR2.0～3.0)进行比较。结果三重抗栓组1年总的出血发生率为17.4%,与双重抗血小板组(4.7%)比较有显著性差异(P<0.05),而与抗凝组(10.9%)比较差异无显著性。严重出血事件三重抗栓组显著高于其他两者(13.3%vs 1.2%,4.7%,P<0.01或0.05)。结论三重抗栓治疗明显增加患者出血的发生率。     

Profile and prevalence of aspirin resistance in patients with metabolic syndrome

Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease,particularly for subjects at high risk such as metabolic syndrome.However,the responsiveness to aspirin treatment may vary among individuals.The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome.Methods In 221 consecutive patients,platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d).Aspirin resistance was defined as mean optical platelet aggregation =20%.Results Aspirin resistance occurred in 39 patients (17.6%).Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6_+0.4g/l vs 2.4±0.4g/L,P=0.017).The 2 groups,aspirin resistance group and no aspirin resistance group,did not differ significantly,with regard to gender,age,body mass index,waist-hip ratio,blood pressure level,serum cholesterol level and history of myocardial or cerebral infarction.Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973,p=0.023).Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%,P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%,P=0.043).But after multifactor logistic regression,in women blood pressure=85mmHg was not a predictor any more.Conclusions In patients with metabolic syndrome,aspirin resistance is not uncommon,especially for men with history of myocardial infarction.Patients with aspirin resistance have an increased serum fibrinogen level.(J Geriatr Cardio12008;5:7-10)     

Prior aspirin use in unstable angina predisposes to higher risk: the aspirin paradox

Background: Aspirin is the most widely prescribed agent used in prevention of coronary thrombosis. Thus, many patients presenting with acute coronary syndromes have a history of aspirin usage. Methods: To assess response to medical therapy in patients taking aspirin prior to admission with an acute coronary syndrome, we reviewed outcomes data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) studies. Results: Patients with acute coronary syndromes who had taken aspirin prior to enrolment were less likely to have non-Q-wave myocardial infarction on admission (ESSENCE: 16.0% vs. 29.2%, p<0.001; PRISM-PLUS: 34.2% vs. 57.7%, p<0.001). However, prior aspirin users were more likely to be failed by standard medical therapy with unfractionated heparin than non-prior aspirin users (ESSENCE: 21.5% vs. 16.5%, p=0.017; PRISM-PLUS: 23.5% vs. 12.1%, p<0.001). Prior aspirin users received greater benefit from both enoxaparin (21.5% vs. 16.8%, p=0.009) and tirofiban with unfractionated heparin (23.5% vs. 16.0%, p=0.007) than from unfractionated heparin alone. Non-prior aspirin users presented with higher rates of non-Q-wave myocardial infarction. Conclusions: Prior aspirin users admitted with acute coronary syndromes may have a more benign presentation, but are more likely to be failed by medical therapy with unfractionated heparin and should be considered as a high-risk group. Enoxaparin or the combination of tirofiban and unfractionated heparin are both more effective than unfractionated heparin in this group.     

Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding

Dual antiplatelet therapy of aspirin and a thienopyridine is the standard of care following coronary stenting. Patients who are on chronic warfarin therapy and receive a coronary stent need to be treated with the triple therapy of aspirin, clopidogrel and warfarin; however, the bleeding risk in these patients is unknown. To evaluate the bleeding risk in patients requiring chronic warfarin therapy and undergoing stent implantation, we compared 107 consecutive patients on chronic warfarin therapy who underwent coronary stenting and were discharged on aspirin, clopidogrel and warfarin to 107 contemporary patients who were treated with aspirin and clopidogrel. We evaluated their bleeding history before and after coronary stenting. Major bleeding was defined as bleeding that was significantly disabling, intraocular or requiring at least 2 units of blood transfusion. Minor bleeding was defined as other bleeding that led to interruption of the medications. Patients on triple therapy were younger and more likely to have hypertension. This group had significantly higher major bleeding (6.6% vs. 0%; p = 0.03) and minor bleeding (14.9% vs. 3.8%; p = 0.01) compared with the dual antiplatelet therapy group. In the triple therapy group, the international normalized ratio or aspirin dosage did not influence the bleeding risk. In patients requiring warfarin therapy, the addition of dual antiplatelet therapy is associated with an approximately 7% major bleeding risk. Thus, novel regimens are needed to reduce the bleeding risk.