Profile and prevalence of aspirin resistance in patients with cardiovascular disease

We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.     

Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR).

Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 +/- 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin-sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy.     

Monitoring of antiplatelet therapy with the PFA-100® in peripheral angioplasty patients

Background: In patients suffering from peripheral arterial occlusive disease (PAOD) the risk of restenosis after percutaneous transluminal angioplasty (PTA) might be influenced by platelet mediated factors. Objective: To look for a correlation between the effect of antiplatelet therapy and recurrence of disease after PTA by monitoring platelet function in 3-month intervals by the platelet function analyzer system, PFA-100®, over a period of 1 year. Patients and methods: A group of 98 patients (43 females, 55 males) with PAOD, treated with aspirin ( n = 52), thienopyridine ( n = 34) or combination therapy of both ( n = 12) were followed over a period of 12 months after elective PTA of the lower extremities with regard to occurrence of restenosis or reocclusion at the site of angioplasty, to demonstrate inhibitory effects on platelets, induced by antiplatelet therapy. Results: PFA-100 proved suitable to identify 'non-responders' to antiplatelet therapy, in a 12-month follow-up period. In 'non-responders' to clopidogrel therapy, a higher incidence of restenosis or reocclusion after PTA of the lower limbs was detected compared with 'responders'. Conclusion: PFA-100, upon stimulation with ADP, might predict patients under clopidogrel therapy with elevated risk for the development of complications following PTA of the lower limbs. This could offer the chance to switch to an alternative therapy or adapt the dose.     

Use of platelet function analyzer PFA-100 and whole blood aggregometry to monitor blood platelet sensitivity to acetylsalicylic acid (aspirin). Is it possible to reliably monitor antiplatelet treatment using routine laboratory diagnostic methods?

Introduction of the antiplatelet agents of new generations and the occurrence of the phenomenon of "aspirin-resistance" triggered the search for better, simpler and more reliable routine diagnostic methods to monitor platelet reactivity. Our objective was to evaluate the usefulness and reliability of two simple methods: platelet function analyzer (PFA-100) and whole blood platelet aggregometry for monitoring of platelet function in 18 healthy blood donors and 35 patients with ischaemic heart disease (IHD) subjected to small doses/75 mg and 150 mg a day) of acetylsalicylic acid (aspirin). In 50% of healthy blood donors the intake of 75 mg ASA a day resulted in the prolongation of PFA-100 collagen/epinephrine closure time (CEPI = (relevant to reduced platelet reactivity) of over 150 s, whereas 75% donors responded to 150 mg ASA-. Otherwise, the daily dose of 150 mg ASA resulted in a prolonged CEPI merely in 23% of in IHD patients. At both doses ASA completely inhibited the arachidonic acid-induced whole blood platelet aggregation in all healthy donors and in all but 3 IHD patients. Collagen-induced platelet aggregation was only negligibly affected by either dose of ASA. Our results point that the simultaneous monitoring of the PFA-100 collagen/epinephrine closure time and whole blood platelet aggregometry (Chrono-Log) enables to reliably evaluate the inhibition of platelet function by ASA and discriminate the partial or complete platelet insensitivity to aspirin. The phenomenon of more frequent platelet aspirin-resistance in IHD patients requires to be verified in randomised clinical prospective studies.     

Effects of aspirin and clopidogrel in healthy men measured by platelet aggregation and PFA-100

There are no generally accepted definitions for low-response (frequently called resistance) to the platelet inhibitors, aspirin and clopidogrel. Low-response may increase the risk of cardiovascular events in atherosclerotic patients. We aimed to define the normal drug responses in healthy men. Platelet function was measured in 20 healthy men during 11 days of aspirin or clopidogrel intake, using light transmission aggregometry (LTA) and the Platelet Function Analyzer 100 (PFA-100). The lower limits for LTA at baseline were 64% and 61%, using arachidonic acid and ADP as agonists, respectively. During aspirin intake the LTA results were stable from day to day, and an upper limit of 9% arachidonic acid stimulated aggregation was found. Clopidogrel intake was best shown by ADP induced aggregation. However, two out of 20 individuals exhibited low-response to clopidogrel. In the remaining 18 volunteers an upper limit of 48% aggregation was found. We found an upper limit for collagen-epinephrine stimulated PFA-100 results of 166 s at baseline. During aspirin intake, these results varied considerably from day to day in nine out of 20 men, resulting in an overlap between the reference ranges at baseline and during therapy. In conclusion, platelet inhibition by aspirin and clopidogrel assessed by aggregometry was stable during 11 days of treatment and reference ranges were established. The PFA-100 results varied greatly and low-response was not precisely defined by this method.     

Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention

Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 micromol/L) and collagen (6 microg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 micromol/L) and thrombin receptor-activating peptide (50 micromol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.     

高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的临床研究

目的对比研究高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的效果及安全性。方法91例高龄老年冠心病患者随机分为氯吡格雷组(50 mg/d)、阿司匹林组(100 mg/d)及对照组(复方丹参滴丸10粒3次/d),药物治疗8周后,观察实验前后血小板聚集率改变、胃黏膜出血、对中性粒细胞及血小板的影响以及凝血三项的改变。结果与对照组比较,氯吡格雷组与阿司匹林组对血小板聚集率均有确切的抑制作用;在血小板聚集率抑制方面,氯吡格雷组优于阿司匹林组;各组实验前后均未出现中性粒细胞及血小板的显著变化;在胃黏膜损伤方面,虽然阿司匹林组发生例数较多,但各组均无显著差异;阿司匹林组及对照组实验前后凝血指标未发生变化,氯吡格雷组用药后活化部分凝血酶时间延长,与对照组比较有显著差异,而用药前两组无显著差异。结论高龄老年应用氯吡格雷与阿司匹林均能获得确切的抗血小板聚集效果,且较安全,其中氯吡格雷效果优于阿司匹林。     

Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin

The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin.     

Clopidogrel anti-platelet effect: an evaluation by optical aggregometry, impedance aggregometry, and the platelet function analyzer (PFA-100)

Platelet aggregation inhibition by clopidogrel may be suboptimal in 4-30% of patients. Traditionally, optical aggregometry is used to assess clopidogrel's anti-platelet effects by inhibition of ADP-induced aggregation in platelet rich plasma. Red blood cells are an important source of ADP and, thus, are known to modulate platelet function. Because the whole blood aggregation by impedance method assesses platelet function in a physiological milieu, we compared clopidogrel response by this method with the optical method in platelet rich plasma (PRP) and the Platelet Function Analyzer (PFA-100). Platelet function studies were performed in 17 healthy subjects at baseline and after 10 days of clopidogrel intake (75 mg/day). Optical and impedance aggregometry were performed after addition of ADP (10 and 20 microM) and collagen (1 and 2 microg/mL). For PFA-100 analysis, whole blood closure time was measured in collagen-coated cartridges with ADP and epinephrine. All subjects except one showed a decrease in ADP-induced aggregation using both aggregation methods. However, ADP-induced platelet aggregation was significantly inhibited when assessed in whole blood as compared to the optical method (71+/- 34% vs. 34.2+/- 23%, p = 0.0002); this suggests that whole blood aggregometry is more sensitive in the detection of clopidogrel effect in the presence of red cells, which are known to modulate platelet function. The PFA-100 ADP closure time was slightly prolonged above the reference interval in only 5/17 (29%) subjects, suggesting that this instrument is not able to detect clopidogrel effect. We conclude that whole blood aggregation appears to be more sensitive in detecting clopidogrel effect compared with the platelet rich plasma method; the PFA-100 was unable to detect clopidogrel effect in the majority of the subjects.     

Residual platelet reactivity is associated with clinical and laboratory characteristics in patients with ischemic heart disease undergoing PCI on dual antiplatelet therapy

A residual platelet reactivity (RPR) on antiplatelet therapy in patients with ischemic heart disease (IHD) has been reported to be associated with adverse clinical events by some Authors. However, scarce data are present on the clinical parameters associated with this phenomenon. No study, at our knowledge, was designed with the specific aim to examine the relationship between clinical characteristics and RPR. We sought to evaluate the clinical and laboratory characteristics associated with RPR in patients with IHD undergoing coronary revascularization on dual (aspirin plus clopidogrel) antiplatelet therapy. We included in the study 868 patients undergoing a coronary angiography: 386 with acute coronary syndromes undergoing a primary coronary revascularization and 482 IHD patients scheduled to undergo an elective coronary angiography. We measured platelet function by both platelet aggregation with two agonists [0.5 mg/mL arachidonic acid (AA); 2 and 10 microM adenosine 5'-diphosphate (ADP)] and a point-of-care assay (PFA-100) on venous blood samples collected within 24 h from the end of the procedure. In patients with acute coronary syndromes and elective PCI diabetes is independently associated with RPR [group A: OR=2.9 (1.5-5.7) by 10 microM ADP, OR=5.3 (1.1-27.8) by PFA-100; group B: OR=4.0 (1.6-10.0) by 10 microM ADP]; reduced left ventricular systolic function [OR=3.7 (2.2-6.5) by AA-PA, OR=2.7 (1.6-4.6) by PFA-100], chronic use of aspirin [OR=0.2 (0.1-0.4) by AA-PA, OR=0.3 (0.2-0.5) by PFA-100] and loading dose of clopidogrel [OR=0.2 (0.06-0.5) by 10 microM ADP] were independent variables significantly associated with RPR in patients undergoing elective PCI. In addition, inflammatory status was found to be significantly associated with RPR in both groups of patients. These results provide indications for the selection of patients for whom the evaluation of platelet reactivity could be useful.     

Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions

Aim Our aim was to evaluate the early efficacy and variabilityof the platelet inhibition exerted by 300 mg clopidogrel forthe purpose of acute percutaneous coronary interventions usingplatelet function tests. Methods and results Elective percutaneous coronary interventionwas used as a timely model in which clopidogrel was added toongoing acetylsalicylic acid (aspirin) (100 mg/day) at 2.5 hprior to procedure. Blood samples were collected before administrationof clopidogrel and immediately before the intervention from50 patients. Platelet functions were assessed with traditionalaggregation and PFA-100^®. At baseline, 14 (28%) patients were poor responders to aspirinaccording to PFA and 9 (18%) continued to show arachidonic acid-inducedaggregation. After clopidogrel ADP-triggered aggregation wasonly modestly inhibited in 40% of the patients. Eight percentof the study population was left without any measurable antiplateleteffect. The patients with modest response to clopidogrel hadhigher levels of c-peptide (1.5 nmol/L) than the ones respondingwell (0.9 nmol/L, ). Conclusion Neither ongoing aspirin treatment nor added clopidogreldid reach an expected extent of platelet inhibition. This studyshows that aspirin-treated patients undergoing PCI gain highlyvariable levels of platelet inhibition with short-term clopidogrel300 mg. At 2 h after adding clopidogrel it failed to enhance platelet inhibition in 40% of the patients.In future, targeted platelet function tests may be helpful toindividually select an effective antiplatelet medication forthese patients. This study suggests that for acute PTCA clopidogreldoes not reach the optimal antithrombotic efficacy in all patients.     

Messung der Thrombozytenfunktion mit Point-of-Care-Methoden

BACKGROUND: More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS: Platelet function analyzer (PFA-100((R))), multiple platelet function analyzer (Multiplate((R))), and rotational thrombelastometry (ROTEM((R))) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS: PFA-100((R)) enables a sensitive detection of von Willebrand's syndrome. Multiplate((R)) is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM((R)) analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM((R)) analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION: Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.     

Cilostazol could ameliorate platelet responsiveness to clopidogrel in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Cilostazol increases the cyclic adenosine monophosphate levels in platelets and might ameliorate the antiplatelet activity of clopidogrel. This study investigated the additional effect of cilostazol on platelet aggregation measured by a VerifyNow analyzer and soluble CD40 ligand (sCD40L) as a marker of activated platelet in patients undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: Sixty cases of primary PCI were randomly assigned to dual (aspirin and clopidogrel) or triple (dual plus cilostazol) therapy. The antiplatelet effects of aspirin and clopidogrel were evaluated by VerifyNow tests. The plasma sCD40L levels at admission, 24 h and 21 days were measured by the ELISA method. The arachidonic acid induced platelet aggregation was similar in both groups. However, the triple group had a significantly lower P2Y12 reaction unit (dual 208.8+/-69.0 vs triple 168.2+/-79.2, p=0.041) and higher % inhibition of adenosine diphosphate (ADP)-induced platelet aggregation (dual 23.8+/-21.4% vs triple 40.5+/-21.0%, p=0.004). In the multivariate analysis, cilostazol was a negative predictor for low responders to clopidogrel (95% confidence interval 0.067-0.711). The plasma sCD40L levels were not significantly different between the 2 groups at the same point of time. CONCLUSIONS: The addition of cilostazol to the combination of aspirin plus clopidogrel significantly increases the inhibition of ADP-induced platelet aggregation. However, there was no additive effect on aspirin-induced antiplatelet activity or lowering of sCD40L.     

Clopidogrel anti-platelet effect: An evaluation by optical aggregometry,impedance aggregometry,and the Platelet Function Analyzer (PFA-100™)

Platelet aggregation inhibition by clopidogrel may be suboptimal in 4–30% of patients. Traditionally, optical aggregometry is used to assess clopidogrel's anti-platelet effects by inhibition of ADP-induced aggregation in platelet rich plasma. Red blood cells are an important source of ADP and, thus, are known to modulate platelet function. Because the whole blood aggregation by impedance method assesses platelet function in a physiological milieu, we compared clopidogrel response by this method with the optical method in platelet rich plasma (PRP) and the Platelet Function Analyzer (PFA-100?). Platelet function studies were performed in 17 healthy subjects at baseline and after 10 days of clopidogrel intake (75?mg/day). Optical and impedance aggregometry were performed after addition of ADP (10 and 20?µM) and collagen (1 and 2?µg/mL). For PFA-100? analysis, whole blood closure time was measured in collagen-coated cartridges with ADP and epinephrine. All subjects except one showed a decrease in ADP-induced aggregation using both aggregation methods. However, ADP-induced platelet aggregation was significantly inhibited when assessed in whole blood as compared to the optical method (71?±?34% vs. 34.2?±?23%, p?=?0.0002); this suggests that whole blood aggregometry is more sensitive in the detection of clopidogrel effect in the presence of red cells, which are known to modulate platelet function. The PFA-100? ADP closure time was slightly prolonged above the reference interval in only 5/17 (29%) subjects, suggesting that this instrument is not able to detect clopidogrel effect. We conclude that whole blood aggregation appears to be more sensitive in detecting clopidogrel effect compared with the platelet rich plasma method; the PFA-100? was unable to detect clopidogrel effect in the majority of the subjects.     

Effect of chronic kidney disease on platelet reactivity to dual-antiplatelet therapy in patients treated with drug-eluting stents

We investigated the effect of chronic kidney disease (CKD) on platelet function in patients receiving dual-antiplatelet therapy after drug-eluting stent (DES) implantation. We examined 19 patients with CKD and 18 patients without CKD who underwent percutaneous coronary intervention (PCI) with DES. All of the patients had been on chronic aspirin treatment. Blood samples were obtained 20-24 h after a loading dose (300 mg) of clopidogrel. Platelet function was evaluated by measuring the closure time (CT) of a collagen/epinephrine (CEPI) or collagen/adenosine diphosphate (CADP) cartridge in the PFA-100 system. Maximum aggregation of agonist (epinephrine, ADP, collagen, or ristocetin)-induced platelet aggregation was also examined by light transmittance aggregometry. The frequency of the poor responders among CKD (n = 9, 47.4%) patients was significantly higher than that among non-CKD patients (n = 2, 11.1%, P = 0.016) as assessed using a CEPI-CT cartridge. Multiple logistic regression analysis revealed that CKD (odds ratio 7.39, 95% confidence interval 1.38-62.09, P = 0.0183] was the only independent determinant of the poor responders. There were no significant differences between the two groups in the value of CADP-CT or in maximum aggregation of epinephrine-, ADP-, collagen-, and ristocetin-induced platelet aggregation. Compared with non-CKD patients, CKD patients had lower response to aspirin therapy as assessed by the PFA-100 system with a CEPI cartridge. On the other hand, the platelet response to dual-antiplatelet therapy was not different between CKD and non-CKD patients.     

Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial.

Several case reports have implicated Ginkgo biloba in clinically adverse bleeding disorders. Ginkgo biloba has been reported to increase pain-free walking distance among patients with peripheral artery disease (PAD). Standard PAD therapy includes 325 mg/day aspirin. The objective of this study was to examine potential adverse effects of concomitant aspirin and Ginkgo biloba on platelet function. Ginkgo biloba (EGb 761, 300 mg/day) was compared with placebo for effects on measures of platelet aggregation among adults consuming 325 mg/day aspirin in a randomized, double-blind, placebo-controlled, parallel design trial of 4-week duration. Participants were adults, age 69 +/- 10 years, with PAD or risk factors for cardiovascular disease. Outcome measures included platelet function analysis (PFA-100 analyzer) using ADP as an agonist (n = 26 placebo; n = 29 ginkgo), and platelet aggregation using ADP, epinephrine, collagen and ristocetin as agonists (n = 21 placebo; n = 23 ginkgo). Participants kept daily logs of bleeding or bruising episodes. There were no clinically or statistically significant differences between treatment groups for any agonists, for either PFA-100 analysis or platelet aggregation. Reports of bleeding or bruising were infrequent and similar for both study groups. In conclusion, in older adults with PAD or cardiovascular disease risk, a relatively high dose of Ginkgo biloba combined with 325 mg/day daily aspirin did not have a clinically or statistically detectable impact on indices of coagulation examined over 4 weeks, compared with the effect of aspirin alone. No adverse bleeding events were observed, although the trial was limited to a small sample size.     

血栓弹力图在急性脑梗死患者抗血小板治疗效果评价中的应用

目的探讨采用血栓弹力图(TEG)评价阿司匹林和氯吡格雷治疗急性脑梗死患者的抗血小板效果,以指导对急性脑梗死患者抗血小板聚集药物治疗的个体化调整。方法选择急性脑梗死患者82例,予阿司匹林100 mg和氯吡格雷75 mg联合治疗7 d后,采用TEG仪检测花生四烯酸(AA)途径诱导的血小板抑制率和腺苷二酸(ADP)受体途径诱导的血小板抑制率,比较患者经两种途径诱导的血小板抑制率以及患者对阿司匹林和氯吡格雷治疗反应的差异。同时选择急性脑梗死患者40例作为对照组,单用阿司匹林100 mg抗血小板治疗7d,对比两组TEG参数(R值、K值、angle角、MA值)。结果急性脑梗死予阿司匹林、氯吡格雷双抗血小板,阿司匹林对AA途径的抑制率明显高于氯吡格雷对ADP受体途径的抑制率,差异有统计学意义(P0.01);对阿司匹林反应良好的患者,4例对氯吡格雷无反应,15例反应低下;对氯吡格雷反应良好的患者,仅1例对阿司匹林反应低下。对氯吡格雷反应低下者,3例对阿司匹林无反应,5例低下,6例对阿司匹林有效,15例良好。两种疗效有一定关联性(P0.01)。对阿司匹林反应良好+有效为62例,反应低下+无效者20例;氯吡格雷反应良好+有效者42例;反应低下+无效者38例,两种药物疗效差异有统计学意义(P0.01)。单用阿司匹林组与双联抗血小板组比较两组患者R值、K值、α角、MA值均无明显差别(P0.05)。结论采用TEG仪检测对急性脑梗死患者抗血小板治疗的疗效评价有较高的临床价值。双联抗血小板中阿司匹林对急性脑梗死患者血小板聚集的抑制作用强于氯吡格雷。患者对阿司匹林和氯吡格雷治疗的反应有差异性,部分对氯吡格雷反应低下者,可能对阿司匹林反应良好或有效。双联抗血小板治疗对血凝的影响较单用阿司匹林无明显差别。     

血栓弹力图检测老年冠心病患者经皮冠状动脉介入治疗后血小板反应性

目的探讨经皮冠状动脉介入治疗术后,经血栓弹力图检测的氯吡格雷药物抵抗患者,不同药物剂量治疗下血小板反应性。方法筛选120例阿司匹林抑制良好而氯吡格雷抑制不敏感的患者,随机分为试验组(60例)和对照组(60例),对照组每天服用100 mg阿司匹林及75 mg氯吡格雷,试验组服用100 mg阿司匹林及150 mg氯吡格雷,检测6个月后氯吡格雷的作用效果,观察2组间6个月内心血管事件及出血事件的发生率。结果试验组心血管死亡、支架内血栓形成、不稳定性心绞痛、心肌梗死发生率分别为0,8.3%,21.7%,8.3%;对照组分别为3.3%,18.3%,35.0%,15.0%,试验组患者氯吡格雷药物抑制率较对照组明显升高(65.6±5.1)% vs (40.9±7.3)%,差异有统计学意义(P0.01)。结论对于血小板高反应性老年患者,每天75 mg氯吡格雷不能满足血小板抑制效果,长期加倍剂量服用能够在一定程度上有效减低药物抵抗发生率,改善血小板抑制效果,从而降低心血管缺血事件的发生率。     

The Role of Exercise on Platelet Aggregation in Patients with Stable Coronary Artery Disease: Exercise Induces Aspirin Resistant Platelet Activation

Objectives: The aim of our study was to determine the relation between exercise stress test and aspirin resistance in patients with stable coronary artery disease.Background: Clinically aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy.Methods: We studied platelet functions of 62 patients with stable coronary artery disease and 20 subjects with normal coronary arteries by Platelet Function Analyzer (PFA-100, Dade Behring, Germany) at rest and after exertion with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP cartridges. Closure time (CT) < 186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. Symptom limited treadmill stress test (protocol of Bruce) was performed with Oxford Streslink TD-1 system.Results: 8 (12.9%) patients were aspirin resistant by PFA-100 (CT < 186s despite regular aspirin therapy) at rest. At the first minute of the recovery period of exercise stress test 14 (22.5%) patients were aspirin resistant by PFA-100. CTs with Col/ADP were respectively 89 ± 6 s (83–100s) and 89 ± 5 s (82–104s) at rest and after exercise (p = 0.107). 20.3% (11/54) of patients known as in vitro aspirin sensitives at rest had shorter CTs and 11.1% (6/54) had aspirin resistance after exercise (p = 0.004). There was no statistically significiant difference in platelet functions in the control group after exertion.Conclusion: We conclude that 11.1% of in vitro aspirin sensitive subjects at rest had aspirin resistance after exercise by PFA-100. In some individuals, exercise induced platelet activation is aspirin insensitive at usual antiplatelet doses. We need further clinical trials to optimize antiplatelet therapy in patients with coronary artery disease.The main supporter of the study was Turkish Society of Cardiology (Istanbul, Turkey). The society is a non-profit association and a member of the European Society of Cardiology. The PFA-100 device and test cartridges are bought with the grant of this non-profit association.