Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy

Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 –VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.     

Differential effect of aspirin on platelet aggregation in patients with coronary artery disease in relation with associated risk factors

Platelets play a key role in the pathogenesis of atherosclerosis and acute coronary syndromes and antiplatelet therapy offers a clinical benefit. Although aspirin is the most widely used agent, there are several conditions in which aspirin may fail to provide a full antithrombotic benefit. Furthermore, data concerning the relationship between platelet function, aspirin, and the associated risk factors are limited. In the present study. ADP and collagen-induced platelet aggregation of 200 consecutive patients with suspected coronary artery disease (CAD) who underwent coronary angiography were evaluated. The patients were classified into three groups according to the number of stenotic vessels. One hundred and eight patients were using 300 mg/day of aspirin. The associated cardiovascular risk factors were also considered. The collagen-induced platelet aggregation of smokers was significantly higher than non-smokers (P < 0.05). Although platelet aggregation was higher in diabetic and hypertensive patients, the difference was not statistically significant. No significant correlation was found between platelet aggregation and other risk factors. The collagen-induced platelet aggregation of the subjects with non-stenotic vessels was reduced by aspirin (P < 0.05). Aspirin did not sufficiently inhibit ADP and collagen-induced aggregation in patients with CAD. This finding supports the idea that the nonplatelet-mediated effects of aspirin could be more important than its antiplatelet effect in clinical use and the use of new potent antiplatelet drugs may complete its antiplatelet effect.     

阿司匹林抑制老年冠心病患者血小板聚集的疗效观察

目的:观察阿司匹林治疗老年冠心病患者24周对血小板聚集功能的影响。方法:选择临床需要服用阿司匹林抗血小板治疗,且ADP诱导的血小板聚集率增高的老年冠心病患者122例,给予阿司匹林100mg口服24周。用药前及用药6、12、24周后分别测定血小板聚集率。结果:服用阿司匹林后,患者的血小板聚集率显著降低,6、12、24周测定血小板聚集率与基线比较均差异有统计学意义(均P<0.01),血小板聚集抑制率分别为-(21.13±21.66)%,-(29.25±21.67)%,-(22.87±21.92)%。12周的血小板聚集率较6周进一步下降,但24周较12周则明显升高,两个差值均差异有统计学意义(均P<0.05)。结论:阿司匹林可明显降低患者的血小板聚集功能,但抗血小板聚集作用在24周后较12周有明显下降。     

Heart rate variability in patients with stable coronary artery disease and aspirin resistance

Aspirin resistance as defined by failure to effectively inhibit thromboxane synthesis is associated with a higher risk of recurrent myocardial ischemia and cardiovascular death. Heart rate variability (HRV) analysis has been extensively used to identify patients at risk for increased cardiac mortality. The aim of this study was to evaluate the association between HRV and aspirin resistance in patients with stable coronary artery disease (CAD). Sixty-nine (69) consecutive patients with stable CAD were included in this study. Of the 69 patients, 18 (26%) were aspirin nonresponders. When the aspirin responders were compared with the nonresponders, there was no significant difference between the groups with respect to most clinical parameters, major cardiovascular risk factors, medical treatments, and aspirin dosages. However, the patients with aspirin resistance had a higher previous myocardial infarction history and lower left ventricular ejection fraction. Moreover, mean platelet volume, CT/EPI, CT/ADP values, LF and LF/HF ratio were higher while HF, SDNN, SDANN, and RMSSD were lower in the nonresponder group than the responders. Regarding HRV parameters, CT/ADP time was negatively correlated with SDNN (r = -0.5, P = 0.02) and HF (r = -0.4, P = 0.03), and positively correlated with LF (r = 0.6, P = 0.01) and LF/HF (r = 0.7, P = 0.001). Similarly, CT/EPI time was negatively correlated with SDNN (r = -0.4, P = 0.03), and positively correlated with LF (r = 0.5, P = 0.02) and the LF/HF ratio (r = 0.5, P = 0.02). Regression analysis revealed that the only parameters affecting SDNN and LF/HF ratio were left ventricle ejection fraction and aspirin resistance. The heart rate variability decreased and sympathetic activity increased in the patients with aspirin resistance and stable CAD. This may contribute to a higher risk of recurrent myocardial ischemia and cardiovascular death in patients with aspirin resistance.     

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.     

Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease

Abstract
Background:   Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardio­vascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation.
Aims:   In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two ­reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in ­platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control.
Results:   ADP- and epinephrine-induced platelet ­aggregation was 78.2 ± 12.8% and 76.7 ± 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 ± 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 ± 11.4% and 50.3 ± 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 ± 11.7% and 38.5 ± 19.8% platelet aggregation with ADP, respectively).
Conclusion:   Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg. (Intern Med J 2003; 33: 350−354)     

The effect of aspirin on mean platelet volume in patients with paroxysmal atrial fibrillation

Aspirin is one of the preferred therapies in the primary prevention of ischemic stroke in paroxysmal atrial fibrillation (PAF). Mean platelet volume (MPV) is a marker of platelet size and activation. Increased MPV reflects active and large platelets. The present observational study was designed to investigate whether aspirin treatment does affect MPV levels in patients with PAF. The study included 101 patients who were detected to have PAF by 24-hour Holter monitoring and divided into two groups based on aspirin treatment [ASA (+) and ASA (?)]. MPV was measured. Patients with aortic and mitral stenosis, hyperthyroidism, hypothyroidism, malignancy, infection, and pregnancy were excluded from the study. Of the 101 patients, 50 had no antiplatelet therapy and 51 had daily aspirin (100?mg) intake. Mean age of the patients was 66?±?10 years and 35 (68%) were male in ASA (+) group. There was no difference in median levels of MPV (9.9 vs. 10.2?fl, respectively; p?=?0.9) between groups. Both uni- and multivariate logistic regression analyses did not show an association between MPV and ASA use. Our results indicate that MPV as a predictive marker of platelet size and activity is not affected by aspirin use in patients with PAF.     

Sex related differences in platelet function: the effect of aspirin

There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.     

Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease

BackgroundPlatelets, long believed to be incapable of de novo protein synthesis, may retain their ability to form the cyclooxygenase (COX) enzyme once it has been inactivated by aspirin. This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients. We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration.MethodsPlatelet responsiveness to aspirin was evaluated in 11 stable coronary artery disease patients on chronic aspirin therapy before and 1, 3, 8, and 24 h after observed ingestion of 80-mg enteric-coated aspirin. Inhibition of the COX pathway was measured pharmacologically through plasma thromboxane (Tx) B₂ levels, and functionally by light transmission aggregometry in response to arachidonic acid. COX-independent platelet activity was measured in response to adenosine diphosphate, epinephrine and collagen.ResultsPlasma TxB₂ levels showed profound inhibition of TxA₂ formation, which was stable throughout 24 h, in all but 1 subject. This subject had optimal response to aspirin (inhibition of platelet TxA₂ production within 1 h), but recovered the ability to synthesize TxA₂ within 24 h of aspirin ingestion. Arachidonic acid-induced platelet aggregation closely mirrored TxB₂ formation in this patient, portraying a functional ability of the platelet to aggregate within 24 h of aspirin ingestion. COX-independent platelet aggregation triggered TxA₂ production to a similar extent in all patients, likely through signal-dependent protein synthesis.ConclusionsCOX-dependent platelet activity is recovered in certain individuals within 24 h of aspirin administration. Further research should consider increasing aspirin dosing frequency to twice daily, to allow sustained inhibition in such subjects.     

Lack of platelet effect with the aspirin analog,salsalate

Platelet function as determined by platelet aggregation and the release reaction was found to be normal in 8 patients receiving a nonacetylated analog of aspirin, salsalate, while all 5 aspirin controls had abnormal platelet function. Mean bleeding time in patients taking salsalate was less than that in aspirin controls. This study demonstrates that salsalate, which has anti-inflammatory activity and reduces prostaglandin synthesis, does not interfere with normal platelet function.     

阿司匹林和氯吡格雷不同服药时间对急性冠状动脉综合征患者血小板聚集率昼夜节律变化的影响

目的 观察急性冠状动脉综合征患者日间、夜间不同时间服用阿司匹林和氯吡格雷对血小板聚集率昼夜变化的影响,确立冠心病患者更有效的服用抗血小板药物时间,提高临床治疗效果.方法 采用交叉试验设计,30例急性冠状动脉综合征患者分别设立为日间服药组(日间组)及夜间服药组(夜间组),于药物达稳态浓度后,用全血阻抗法以ADP及花生四烯酸为诱导剂检测24 h内5个时间点血小板聚集率.之后,两组交换,药物达稳态浓度后以相同方法再次测定24 h内5个时间点血小板聚集率.结果 花生四烯酸诱导的血小板聚集率,日间组10:00时最高[(7.96±3.64)欧姆],00:00时最低[(6.12±3.29)欧姆],两者比较差异无统计学意义(P＞0.05);夜间组20:00时最高[(7.86±4.28)欧姆],10:00时最低[(5.46±3.93)欧姆],两者比较差异有统计学意义(P＜0.05).ADP诱导的血小板聚集率,日间组10:00时最高[(9.93±5.73)欧姆],16:00时最低[(9.14±5.13)欧姆],两者比较差异无统计学意义(P＞0.05);夜间组20:00时最高[(9.40±5.39)欧姆],10:00时最低[(7.37±4.12)欧姆],差异无统计学意义(P＞0.05).同一时间点两组之间比较,2种诱导剂测定的血小板聚集率在10:00时日间组均明显高于夜间组(P＜0.05),其余4个时间点之间两组比较差异均无统计学意义.结论 日间服药与夜间服药血小板聚集率呈现不同的昼夜变化规律,夜间服用阿司匹林及氯吡格雷可抑制晨起血小板聚集高峰,夜间服药优于日间服药.     

Low-dose aspirin increases aspirin resistance in patients with coronary artery disease

PURPOSE: We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. METHODS: We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) > or =550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009) and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.     

Response variability to aspirin and one-year prediction of vascular events in patients with stable coronary artery disease

The aim of this study was to assess the association between “aspirin non responsiveness” in patients with coronary artery diseases (CAD) and the risk of major adverse cardiovascular events (MACE). 204 patients with CAD receiving aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI-CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the patients aspirin responsiveness. The clinical primary endpoint was the occurrence of MACE including: cardiovascular death, MI, stroke or transient ischemic attack. The secondary endpoint was the occurrence of Recurrent Acute Vascular Event (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%; P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7–2.4; P = 0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2–32.2; P = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated with an increased risk of either MACE or RAVE. Our results, reinforce the importance of being able to diagnose laboratory “aspirin non responsiveness”, and extend the evidence that aspirin non responsiveness may explain in part the occurrence of RAVE.     

Effect of high dose statin therapy on platelet function; statins reduce aspirin resistant platelet aggregation in patients with coronary heart disease

Background Current evidence supports the preventive role of statins on platelet aggregation in patients with coronary heart disease. Aim Our aim was to determine the effects of aggressive statin therapy on platelet function in patients with coronary heart disease. Material and methods A total of 178 consecutive patients (37–68 years old, 35.9% women) with stable coronary artery disease (CAD) was enrolled in the study. Platelet function assays were realized by the Platelet Function Analyzer (PFA)-100 with collagen and epinephrine (Col/Epi) and collagen and ADP (Col/ADP) cartridges. Aspirin resistance was defined as having a closure time (CT) of <186 s with Col/Epi cartridges despite regular aspirin therapy. A statin therapy protocol applied to the patients with aspirin resistance for 3 months. Results We determined that 20 (11.2%) of patients had aspirin resistance by the PFA-100. Mean closure time measured with the Col/ADP cartridges was 83 ± 18 s (53–162 s). Of the patients 12 were not on a statin therapy and eight were taking 10 mg daily atorvastatin. After 3 months of 40 mg daily atorvastatin therapy 13 subjects with aspirin resistance became aspirin sensitive by PFA-100 (P < 0.0001). There was also a significant decrease in total and LDL cholesterol levels and an increase in HDL cholesterol at the third month of statin therapy (P < 0.0001 for all). Conclusion Statin therapy reduced the in vitro aspirin resistance in 65% of the patients after a therapy of 3 months. Further studies are needed to elucidate the mechanism of statins’ effects on platelet reactivity.     

Evaluation of platelet function in aspirin treated patients with CAD

Background: Studies of platelet function in the acute coronary syndrome (ACS) have revealed both increased and unchanged platelet activation. To obtain a better understanding of platelet function in coronary artery disease in the setting of aspirin therapy, we performed platelet functional testing in patients with ACS and compared results to patients without CAD. Methods: We measured platelet aggregation and activation in response to ADP and epinephrine in 80 age and gender matched hospitalized patients (40 with ACS, 40 with non-cardiac chest pain (NCCP)). All subjects received ASA (81–325 mg). Platelet aggregation was performed using standard light transmission in platelet-rich plasma and activation was measured via flow cytometric analyses. We also studied platelet function under high shear rates measured by the platelet function analyzer (PFA-100). Results: ASA effect was found to be present in all subjects by blunted platelet aggregation in response to arachidonic acid. Patients with ACS showed significantly higher levels of platelet aggregation to epinephrine compared to patients with NCCP (p = 0.001). Other measures of platelet function including ADP aggregation, Pselectin, activated glycoprotein IIb/IIIa expression, and PFA-100 were unchanged between the two groups. Conclusions: We have found conflicting results of platelet functional testing in ACS. Specifically aspirin therapy in patients with ACS is effective in suppressing the platelet release response and is effective in the partial suppression of platelet aggregation; however, it appears that ACS patients have increased platelet aggregation to adrenergic stimuli when compared to age and gender matched controls without CAD despite the use of aspirin. In some studies, because ACS patients have an accentuated response to adrenergic stimuli this might be interpreted as aspirin resistance. Our study suggests that depending on the assay used to determine aspirin resistance, not all patients with this label are resistant to the biological effects of aspirin but they may have higher than normal baseline platelet sensitivity to adrenergic stimuli. This research was supported by grant K23HL67066 from the National Institute of Health.     

Fast platelet suppression by lysine acetylsalicylate in chronic stable coronary patients. Potential clinical impact over regular aspirin for coronary syndromes

BACKGROUND: The rapid utilization of fibrinolytics following Q-wave myocardial infarction has clearly modified the evolution of this disease. However, it is still not known whether the immediate inhibition of platelet aggregation (PA) during the coronary event improves outcomes. HYPOTHESIS: The present study was designed to test, in patients with known coronary artery disease (chronic stable angina), whether the particular kinetic pattern of lysine acetylsalicylate (LA) compared with aspirin may affect the time to onset of inhibition of platelet aggregation. METHODS: Ten patients suffering from chronic stable angina participated in this study to compare the efficacy and speed of the inhibition of PA with 320 mg of LA versus 320 mg of aspirin. All patients discontinued the use of aspirin and any other anti-inflammatory agents for 15 days prior to the beginning of the study. They were randomly assigned to LA or aspirin. Blood specimens were obtained to measure the PA at admission, and 5, 10, 20, 30, and 60 min after ingestion. Patients continued to take the assigned drug once a day for the following 4 days. On Day 5, a new blood sample was taken. After this, patients underwent a 15-day wash-out period, and then crossed over to the opposite drug. The samples were analyzed immediately using platelet-rich plasma stimulated with adenosine diphosphate (ADP) 2 mumol/l, collagen 1 microgram/ml, epinephrine 20 mumol/l, and sodium arachidonate acid 0.75 mm/l. RESULTS: The same level of PA inhibition after 30 and 60 min of aspirin administration can be obtained with LA 5 min following ingestion (sodium arachidonate acid: LA: 16.3 +/- 25.9 vs. aspirin 57.6 +/- 8.2; p = 0.00014; collagen: LA 18.9 +/- 20.1 vs. aspirin 47.2 +/- 10.5; p = 0.00092; ADP: LA 27.3 +/- 18.4 vs. aspirin 39.7 +/- 21.8, p = 0.18; epinephrine: LA 22.0 +/- 9.9 vs. aspirin 55.4 +/- 10.9, p = 0.00002. CONCLUSIONS: Platelet aggregation inhibition immediately following LA may have significant clinical implications for the treatment of coronary syndromes.     

阿司匹林和西洛他唑对冠心病合并糖尿病患者血小板聚集活性的影响

目的:探讨阿司匹林对冠心病合并糖尿病患者血小板聚集活性的影响;西洛他唑对血小板聚集活性作用是否有类似改变。方法:入选的冠心病患者中合并与合并2型糖尿病患者各45例。根据其口服药物又分为阿司匹林组、西洛他唑组和联合用药组,每组各15例。记录患者基本情况并测定血小板聚集活性、血浆血栓素(TX)B2、6-K-前列腺素(PG)F1a和髓过氧化物酶(MPO)水平,并进行统计分析。结果:(1)多元逐步回归分析显示血糖是影响血小板聚集的独立因素(R=0.914,P<0.01);(2)方差分析显示糖尿病患者血小板聚集活性、血浆TXB2、MPO水平较非糖尿病患者明显增高,6-K-PGF1a水平降低(P<0.001);(3)非糖尿病患者阿司匹林组和西洛他唑组血小板聚集活性和TXB2没有明显差异,西洛他唑组血浆6-K-PGF1a水平高于阿司匹林组,而MPO水平低于阿司匹林组(P<0.001);糖尿病患者西洛他唑组血小板聚集活性、TXB2和MPO水平低于阿司匹林组,而6-K-PGF1a水平高于阿司匹林组(P<0.05~0.001)。结论:对冠心病合并糖尿病患者西洛他唑较阿司匹林可以更有效地抑制血小板聚集。