Long-term outcome in patients with unstable angina treated by coronary balloon angioplasty

Comparison of balloon angioplasty results in 472 patients with stable angina (SA) and 158 patients with unstable angina (UA) in 5-year follow-up is reported. Clinical success rate did not differ significantly, while periprocedural complications rate was higher in UA group (22.3 vs. 11.1%, P<0.001). During follow-up UA patients demonstrated higher: restenosis rate (48.5 vs. 30.4%, P<0.001), incidence of myocardial infarction (8.8 vs. 3.0%, P=0.004), although cardiac mortality did not differ significantly (2.2 vs. 1.6%). Reintervention rate in patients with unstable angina resultant from restenosis or significant artherosclerosis progression in coronary vessels, or originating from both of them, was also higher (53.7 vs. 34.1%, P<0.001). Event-free survival was significantly lower in UA patients (43.4 vs. 61.3%, P=0.02). The uni- and multivariate analysis proved that unstable angina was an independent risk factor in restenosis, re-intervention and cardiac events rate, despite perceptible differences in the baseline characteristics. Sub-group analysis of UA patients according to Braunwald classification revealed lower success rate and higher incidence of myocardial infarction during follow-up in post-infarction angina (class C), whereas new onset, no-rest angina (class I) had higher event-free survival in comparison with rest angina (classes II and III). CONCLUSIONS: UA patients treated by balloon angioplasty had higher periprocedural complications rate, as well as restenosis and re-intervention rate. Despite higher cardiovascular events rate during 5-year follow-up in UA group, survival rate in both groups was high and cardiac mortality did not differ significantly. Unstable angina constitutes a strong independent risk factor in adverse long-term outcome.     

Relation of low response to clopidogrel assessed with point-of-care assay to periprocedural myonecrosis in patients undergoing elective coronary stenting for stable angina pectoris

Impaired responses to antiplatelet therapy assessed by laboratory tests are associated with an increased risk of recurrent ischemic events after percutaneous coronary intervention (PCI). This study was designed to determine the relation between responses to aspirin and clopidogrel as assessed by a point-of-care assay (Verify Now, Accumetrics, San Diego, California) and periprocedural myocardial infarction (PMI) in patients undergoing elective PCI for stable angina. One hundred twenty-two consecutive patients undergoing elective coronary stenting prospectively received aspirin 500 mg and clopidogrel 600 mg >or=12 hours before PCI. Clopidogrel response was measured with P2Y12 reaction units (PRUs) and percent inhibition P2Y12 from baseline (percent inhibition P2Y12) and aspirin response with aspirin reaction units (ARUs). Troponin T level was considered positive if it was >0.03 ng/ml. Responses to aspirin and clopidogrel were correlated (r=0.42, p <0.0001). PMI occurred in 27 patients (22%) who showed significantly lower percent inhibition P2Y12 (25.3+/-26 vs 38.3+/-25, p=0.01) and a trend toward higher PRU values (221+/-87 vs 193+/-94, p=0.21). We did not find any difference for aspirin response as assessed by ARUs in patients with or without PMI (460+/-82 vs 454+/-73, p = 0.82). Stratification of percent inhibition P2Y12 isolated a quartile of clopidogrel nonresponders (inhibition P2Y12 <15%) with significantly higher incidence of PMI (44% vs 15%, odds ratio 4.6, 95% confidence interval 1.9 to 11.5, p=0.001). In conclusion, point-of-care assessment of clopidogrel response reliably predicted PMI after low- to medium-risk elective PCI for stable angina.     

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7 +/- 8 and 67.5 +/- 8 years in UA and SA, respectively (P = 0.93). Closure time was significantly reduced in UA patients (78.8 +/- 14 s), compared to SA patients (93.3 +/- 19 s, P < 0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1 mg/l (bottom and top quartile levels, 1.50-7.95). There was no significant correlation between closure time and CRP levels (r = 0.22, P = 0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.     

不稳定性心绞痛冠状动脉造影病变与临床的相关性

目的：分析不稳定性心绞痛（UA）临床表现,心电图与冠状动脉（冠脉）造影病变形态的关系。确定不稳定性病变及住心院心脏事件的临床预测因子,方法：选择冠脉造影异常（血管狭窄≥50％）的住院UA病人120例,观察不同Braunwald分级病人造影病变形态等的发生率,评估心电图ST段异常对复杂病变、住院心脏事件等的预测价值。结果：复杂病变的检出率Ⅲ级（20／33例）最高,较Ⅰ级（13／43例）差异有显著性（P＜0．05）,血栓的检出率Ⅲ级（6／33例）亦高于Ⅰ、Ⅱ级,与Ⅱ级（1／44例,2％）比较差异有显著性（P＜0．05）。住院心脏事件发生率Ⅲ级明显高于Ⅰ级（58％与195,P＜0．01）与Ⅱ级（58％与25％,P＜0．01）。Logistic回归分析示,心电图ST段异常及BraunwaldⅢ级均能预测复杂病变的存在（P＜0．01,OR为4．9;P＜0．01,OR为3．3）,心电图异常能预测三支病变（P＜0．01,OR为3．9）和心脏事件（P＜0．01,OR为4．8）。结论心电图ST段异常及48h内发作的静息心绞痛对复杂病变有预测价值。ST段异常的病人,三支血管病及发生心脏事件的危险性高。     

Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease.

AIMS: This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD). METHODS AND RESULTS: Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007). CONCLUSION: In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.     

Serial changes in platelet activation in patients with unstable angina following coronary stenting: evaluation of the effects of clopidogrel loading dose in inhibiting platelet activation.

BACKGROUND: Platelet activation is crucial in the development of acute or subacute stent thrombosis following implantation. This study investigated whether a conventional regimen comprising a loading dose of 300 mg of clopidogrel, followed by daily doses of 75 mg, could significantly suppress platelet activation in patients with unstable angina (UA) undergoing coronary stenting. METHODS AND RESULTS: Platelet activation (expressed by CD62p) was serially examined using flow cytometry in 42 consecutive patients with UA who underwent coronary stenting. CD62p expression was also evaluated in 30 normal control subjects. CD62p expression was markedly higher pre-procedure in the study patients than in the normal control subjects (5.2+/-4.0% vs 1.4+/-0.6%, p<0.0001). CD62p expression in the study patients remained significantly higher at 24 h after the procedure than in the control subjects (3.8+/-2.1% vs 1.4+/-0.6%, p<0.001). Additionally, only 26% of CD62p expression (5.2% vs 3.8%, p=0.026) in the study patients was suppressed at 24 h after the procedure. However, more than 60% of CD62p expression (5.2% vs 2.0%, p<0.0001) was suppressed on day 7 after the procedure. CONCLUSION: Less than one-third of CD62p expression was suppressed at 24 h by the conventional loading dose (300 mg) of clopidogrel in patients with UA following coronary stenting. This finding indicates the need to evaluate whether an increased loading dose of clopidogrel would be a more efficacious and safe regimen for patients in this clinical setting.     

Clopidogrel loading dose (300 versus 600 mg) strategies for patients with stable angina pectoris subjected to percutaneous coronary intervention

We evaluated the effect of high versus low loading doses of clopidogrel in patients with stable angina pectoris who underwent percutaneous coronary intervention (PCI) on periprocedural events, in-hospital complications, and 30-day outcomes. The recommended loading dose of clopidogrel for patients with PCI is currently 300 mg. Recent studies have suggested that 600 mg may decrease periprocedural complications in patients with unstable angina. However, whether this holds for patients with stable angina pectoris is unknown. We reviewed records of 445 patients with stable angina pectoris who underwent PCI and were loaded with 300 mg (n = 126) or 600 mg (n = 319) of clopidogrel immediately before the procedure. Study end points were periprocedural ischemic events, bleeding complications, and a composite of major adverse cardiac events at 30 days. Baseline characteristics and procedural indexes were similar between groups. Major in-hospital complications were recorded in 2 patients in the 600-mg group and in no patient in the 300-mg group (p = 1.00). Postprocedural increase of cardiac enzymes (troponin I, p = 0.91; creatinine kinase-MB, p = 0.395) and major bleeding (0.6% vs 0%, p = 1.00) were comparable, as was 30-day major adverse cardiac events (1.2% vs 0%, p = 0.56). Multivariate analysis did not identify any risk decrease for periprocedural myocardial infarction with 600 mg of clopidogrel (odds ratio 2.68, 95% confidence interval 0.74 to 9.78, p = 0.135). In conclusion, in patients with stable angina pectoris, a 300-mg clopidogrel loading dose, when given immediately before PCI, is sufficient. Although 600 mg was clinically safe, it was not associated with fewer periprocedural events and improved 30-day outcomes compared with 300 mg.     

A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days.

AIMS: We sought to test whether an increase in the clopidogrel maintenance dose results in increased inhibition of platelet aggregation. METHODS AND RESULTS: Sixty patients after pre-treatment with 600 mg of clopidogrel and within 12 h after successful PCI were included in this trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a double-blind randomized manner. Platelet function was evaluated 30 days after the intervention with optical aggregometry and with a new point-of-care test (VerifyNowtrade mark P2Y12 assay). Maximal 5 microM ADP-induced platelet aggregation 30 days after PCI in the group treated with 150 mg/day clopidogrel (45.1 +/- 20.9%) was significantly lower than in the group treated with 75 mg/day (65.3 +/- 12.1%; P < 0.001). The VerifyNowtrade mark P2Y12 assay also indicated a higher degree of platelet function inhibition in the group treated with 150 mg/day (60.0 +/- 72.0 P2Y12 Reaction Units) than in the group treated with 75 mg/day (117.0 +/- 64.3 P2Y12 Reaction Units; P = 0.004). CONCLUSION: Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense inhibition of platelet aggregation than administration of the currently recommended 75 mg maintenance dose.     

他汀类药对氯吡格雷抗血小板作用的影响

目的 前瞻性评价普伐他汀、氟伐他汀、阿托伐他汀对氯吡格雷抗血小板作用的影响.方法 人选连续1015例急性冠状动脉综合征或稳定性心绞痛行冠状动脉造影和(或)支架术患者,分为普伐他汀组(228例)、氟伐他汀组(179例)、阿托伐他汀组(481例)和对照组(127例).比较各组术后支架内血栓发生率、不同浓度(2、5、10、20 μmol)二磷酸腺苷(ADP)诱导的1 min(ADP-1)、5 min(ADP-5)和最大血小板聚集力(ADP-M)及其影响因素.结果 4组患者基础临床情况(除年龄、高血压及冠状动脉造影复查率外)和冠状动脉病变和(或)支架术情况相似,术后支架内血栓发生率(普伐他汀组0.9%、氟伐他汀组1.1%、阿托伐他汀组1.0%、对照组0.8%,P>0.05)和ADP-1、ADP-5、ADP-M与对照组相比差异均无统计学意义(P均>0.05).多因素回归分析显示,年龄(B=0.21,P=0.001)、氯吡格雷总量(B=7.30,P=0.002)及低分子肝素的使用(OR=6.71,P=0.01)是影响氯吡格雷抗血小板作用的独立决定因素.结论 普伐他汀、氟伐他汀和阿托伐他汀对氯吡格雷的抗血小板作用无明显影响,而年龄、氯吡格雷总量及低分子肝素使用是决定氯吡格雷抗血小板作用的独立因素.     

国产氯吡格雷个体化用药在经皮冠状动脉介入术患者中使用的评价

目的通过观察经皮冠状动脉介入治疗（PCI）患者常规使用氯吡格雷后的血小板聚集率情况,并根据血小板聚集率以及是否存在PCI术后支架内血栓形成的高危因素来个体化调整氯吡格雷的使用剂量,以评价氯吡格雷的个体化用药在PCI术患者中使用的疗效及安全性。方法将在我院行PCI术的冠心病患者182例随机分为个体化用药组（88例）和常规用药组（94例）,两组术前3天起常规服用阿司匹林100 mg/d＋氯吡格雷75 mg/d或术前顿服阿司匹林300 mg＋氯吡格雷300 mg,术后两组均予氯吡格雷75 mg/d。常规用药组使用氯吡格雷75 mg/d维持至术后一年。而个体化用药组则可根据患者的血小板聚集率以及是否存在PCI术后支架内血栓形成的高危因素来调整氯吡格雷的用量。结果个体化用药组的出血并发症明显少于常规用药组（2/88比12/94,P〈0.01）。两组间主要心血管不良事件（MACE）的发生率差异无统计学意义（P〉0.05）,支架内再狭窄发生率差异无统计学意义（2/33比3/38,P〉0.05）。结论国产氯吡格雷在PCI患者中使用是有效并且安全的,而个体化调整氯吡格雷剂量能更进一步减少并发症,增加安全性。