经皮冠状动脉介入治疗中氯吡格雷应用进展

由于置入技术的日益成熟、器械的改进以及相关药物治疗的研发进展，使经皮冠状动脉介入治疗（peri—percutaneous coronary intervertion，PCI）的成功率高、并发症发生率低的优点得到进一步体现。随着PCI的开展，支架内血栓的形成越来越受到重视，尤其药物洗脱支架（DES）置入增多，术后支架内血栓事件增多，一旦发生就会造成严重的后果，它可以导致20％的患者猝死，60％～70％的患者发生急性心肌梗死。支架内血栓形成的主要原因是血小板的黏附和聚集以及由血小板诱发的血栓形成。     

Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction

Pretreatment with clopidogrel before elective primary percutaneous coronary intervention (PCI) has been shown to reduce ischemic complications. There are limited data about the value of clopidogrel pretreatment in the setting of PCI for ST-elevation myocardial infarction (STEMI). We aimed to examine the effect of clopidogrel preloading on angiographic and clinical outcomes in patients with STEMI who were treated with PCI. We conducted a prospective registry of all patients treated with primary PCI for STEMI from March 2003 to June 2006. Excluded were patients with cardiogenic shock. For the current analysis, patients (n = 292) were allocated into 2 groups. One group received clopidogrel loading dose before PCI (in the emergency department or coronary care unit, n = 165); the other,immediately after PCI (n = 127). TIMI myocardial perfusion (TMP) grade at the end of PCI and 30-day and 6-month clinical outcomes were assessed. Clinical characteristics were similar among the groups. However, patients pretreated with clopidogrel were more likely to receive aspirin and beta blockers before the current admission. TMP grade 3 occurred in a higher proportion of patients in the clopidogrel pretreatment group than in the no-pretreatment group (85% vs 71%, p = 0.01). Multivariate logistic regression analysis showed that clopidogrel pretreatment was associated with an odds ratio of 2.2 for TMP grade 3 (1.2 to 3.9, p = 0.01). Furthermore, the incidence of reinfarction at 30 days was lower in the pretreatment group (0% vs 3.2%, respectively, p = 0.04). In conclusion, these findings support the early use of clopidogrel in patients with STEMI who are treated with primary PCI.     

Meta-analysis appraising high clopidogrel loading in patients undergoing percutaneous coronary intervention

Combined antiplatelet treatment with aspirin and clopidogrel is pivotal to minimize periprocedural adverse events in patients who undergo percutaneous coronary intervention. However, there is debate on the best clopidogrel loading dose. The investigators performed a systematic review and meta-analysis of the optimal clopidogrel loading dose. Pertinent trials comparing high (>300 mg) and standard (300 mg) clopidogrel loading doses in patients scheduled for catheterization and/or percutaneous coronary intervention were systematically searched in BioMedCentral, CENTRAL, Google Scholar, and PubMed (December 2006). The primary end point was the 1-month rate of death or myocardial infarction. Secondary end points included other ischemic and bleeding adverse effects. Peto odds ratios were computed. A total of 10 studies (7 randomized, 3 nonrandomized) were included, enrolling 1,567 patients (712 loaded with 300 mg, 11 with 450 mg, 790 with 600 mg, and 54 with 900 mg). Overall, a high loading dose proved significantly superior to a standard loading dose in preventing cardiac death or nonfatal myocardial infarction (odds ratio 0.54, 95% confidence interval 0.32 to 0.90, p = 0.02), without any statistically significant increase in major or minor bleedings (p = 0.55 and p = 0.98, respectively). Sensitivity analysis restricted to randomized trials confirmed the superiority of a high loading dose regimen (p = 0.0031). Meta-regression disclosed a significant interaction between event rate and the benefits of high loading doses (p = 0.005), suggesting that the greater the underlying risk, the greater the favorable impact of a high loading dose. In conclusion, a high clopidogrel loading dose (>300 mg) significantly reduces early ischemic events in patients scheduled for percutaneous coronary intervention.     

Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention

This study sought to determine the effect of clopidogrel pretreatment on the increase in C-reactive protein (CRP) after percutaneous coronary intervention. Clopidogrel pretreatment attenuated the periprocedural increase in CRP by 65% and was independently associated with an attenuation in the CRP increase in a multivariate model.     

经皮冠状动脉介入术后氯吡格雷抵抗的临床观察

目的观察因急性冠脉综合征（ACS）行冠状动脉介入治疗（PCI）患者应用氯吡格雷后血小板聚集率的变化及氯吡格雷抵抗的发生情况。方法ACS患者37例,予氯吡格雷负荷量300mg,继予75mg/d维持,在服用氯吡格雷前,服药后2、4、6、24、48h以及服药后30d取血,测定ADP诱导的血小板聚集率,观察血小板聚集率变化并根据抑制程度判断氯吡格雷抵抗发生率。结果给药后2、4、6、24、48h及30d时,氯吡格雷抵抗的发生率分别为62%、46%、32%、38%、49%和43%,氯吡格雷抵抗者用药后血小板抑制率明显低于反应者,其中1例抵抗者出现亚急性支架内血栓形成。结论PCI治疗的部分患者中存在氯吡格雷抵抗。     

国产氯吡格雷对急性冠脉综合征经皮冠脉介入术的疗效

目的：研究国产氯吡格雷用于非ST段抬高急性冠脉综合征（NSTEACS）急诊经皮冠脉介入（PCI）治疗患者的疗效及安全性。方法：确诊NSTEACS并接受急诊PCI的患者176例,分成国产氯吡格雷组（接受泰嘉治疗,89例）和进口氯吡咯雷组（接受波立维治疗,87例）。PCI治疗前两组分别接受泰嘉、波立维每日600mg。PCI后每日分别接受75mg至1年以上。观察两组患者的疗效及不良反应的发生情况。结果：国产氯吡格雷组与进口氯吡格雷组达到的完全血运重建率（79．8％比89．3％．P=0．477）,主要不良心脑血管事件（MACCE）发生率（9．0％比6．9％,P=0．608）,不良反应的发生率（5．6％比8．0％,P=0．523）均无显著差异。结论：国产氯吡格雷（泰嘉）治疗急性非ST段抬高心肌梗死的疗效和安全性与进口氯吡格雷相当。     

早期服用氯吡格雷对急性冠状动脉综合征患者介入治疗近期临床预后的影响

目的探讨冠状动脉(冠脉)介入治疗(PCI)术前早期使用氯吡格雷能否较术前临时用药进一步改善非ST段抬高的急性冠脉综合征(NSTE-ACS)患者的近期预后。方法将拟行早期PCI治疗的NSTE-ACS患者随机分为早期用药组和对照组。早期用药组272名患者于入院临床诊断明确后立即开始服用氯吡格雷(首次给负荷量300mg,后以75mg/d维持)。对照组共入选265名患者,于冠脉造影后决定选择PCI治疗时开始用药,首次服用氯吡格雷300mg,术后以75mg/d维持。比较两组在PCI术后30d内死亡、支架血栓、心肌梗死、再发心绞痛和靶血管血运重建等心脏不良事件(MACE)的发生率。结果两组患者在临床病情、冠脉病变及支架置入治疗等方面比较,差异无统计学意义。PCI术后30d内早期用药组死亡、支架血栓、心肌梗死和靶血管血运重建等联合事件的发生率显著低于对照组。结论PCI术前早期使用氯吡格雷能够明显减少NSTE-ACS患者心血管不良事件的发生率,显著改善患者PCI术后的近期预后。     

老年冠心病患者行经皮冠状动脉介入术术前强化他汀治疗的有效性和安全性研究

目的:探讨经皮冠状动脉介入(PCI)术前,负荷剂量阿托伐他汀的强化治疗,对高龄老年冠心病患者预后的影响。方法:入选年龄在70~82岁择期行PCI的患者共300例,随机分为常规治疗组和强化治疗组,观察术后心肌标志物及高敏C反应蛋白(hs-CRP)的水平变化及术后1个月和12个月主要不良心脏事件(MACE,包括心源性死亡、心肌梗死和靶血管血运重建)的发生率。结果:常规治疗组术后24 h c TNI和hs-CRP高于强化治疗组(P=0.04和P=0.01)。强化他汀治疗组PCI术后与PCI相关心肌梗死发生率明显低于常规治疗组(12.1%vs.21.8%,P=0.047)。强化他汀治疗组中12个月时LDL≤1.8 mmol/L比率更高(10.1%vs.4.0%,P=0.04)。12个月时MACE事件发生率强化治疗组低于常规治疗组(9.4%vs.17.2%,P=0.046)。结论:高龄冠心病患者择期PCI术前强化阿托伐他汀钙80 mg/d可以显著减少与PCI相关的心肌梗死,并且安全性良好。     

Effect of coronary endothelial function on outcomes in patients undergoing percutaneous coronary intervention

Numerous studies have documented the association between endothelial dysfunction and adverse cardiovascular events. For example, coronary artery disease is associated with functional and structural changes of the coronary arteries, resulting in ischemia or plaque rupture, and is highly associated with endothelial dysfunction. Recent data suggest that implantation of drug-eluting stents (DES) can induce coronary artery endothelial dysfunction at follow-up when compared with bare-metal stents (BMS) and that this endothelial dysfunction may be associated with late stent thrombosis. Indeed, despite the superiority of DES in preventing restenosis, the incidence of death and myocardial infarction is similar when comparing DES with BMS. Medical treatment, such as statins, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, can improve endothelial dysfunction. Thus, administration of these drugs along with percutaneous coronary intervention (PCI) may be a low-risk strategy to provide therapeutic benefit by stabilizing unstable plaque or by suppressing new lesion formation in patients undergoing PCI.     

替格瑞洛与氯吡格雷在非氯吡格雷抵抗PCI患者术后的应用效果

目的对比非氯吡格雷抵抗ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入(PCI)术后长期服用替格瑞洛与氯吡格雷的疗效与安全性。方法 121例PCI患者随机分为替格瑞洛组(60例)与氯吡格雷组(61例),在口服阿司匹林基础上,替格瑞洛组术后加服替格瑞洛抗血小板治疗,每日2次,每次90 mg;氯吡格雷组加服氯吡格雷治疗,75 mg/d,随访两组术后半年血小板抑制情况、血液流变学指标及血栓标志物变化情况,比较术后1年内出血及主要不良心血管事件(MACE)发生率。结果替格瑞洛组术后半年二磷酸腺苷(ADP)诱导的血小板抑制率〔(17. 3±4. 4) vs(13. 5±3. 8)%〕及全血高切黏度〔(0. 85±0. 18) vs(0. 67±0. 20) m Pa·s〕、低切黏度〔(1. 06±0. 21) vs(0. 89±0. 24) m Pa·s〕、血浆黏度〔(0. 43±0. 10)vs(0. 35±0. 08) m Pa·s〕下降绝对数值均显著高于氯吡格雷组(P均<0. 05);替格瑞洛组术后半年金属基质蛋白酶-9〔(102. 5±26. 7) vs(91. 8±22. 3) mg/L〕、D-二聚体〔(106. 3±21. 5) vs(94. 1±20. 5)μg/L〕、瘦素〔(3. 27±0. 95) vs(2. 89±0. 87)μg/L〕下降绝对数值显著高于氯吡格雷组(P均<0. 05);替格瑞洛组与氯吡格雷组术后1年内出血发生率(14. 0%vs 10. 2%)差异无统计学意义(P>0. 05),替格瑞洛组呼吸困难发生率显著高于氯吡格雷组(15. 8%vs 3. 4%,P<0. 05),而氯吡格雷组术后MACE发生率显著高于替格瑞洛组(16. 9%vs 5. 3%,P<0. 05)。结论对非氯吡格雷抵抗者,替格瑞洛、氯吡格雷分别联合阿司匹林均是PCI术后抗血小板治疗的有效方案,前者能在不明显增加出血事件前提下,降低血小板反应性与血液黏度,并表现出减少MACE的趋势。     

Traditional clinical risk factors predict clopidogrel hypo-responsiveness in unselected patients undergoing non-emergent percutaneous coronary intervention

High and low platelet reactivity, HPR and LPR respectively, to clopidogrel and aspirin have previously been associated with adverse events following percutaneous coronary intervention (PCI). The aim is to test the ability of a previously developed clinical risk-score, the PREDICT score, to identify patients with HPR and LPR. Nine hundred and twenty-three consecutive patients undergoing non-emergent PCI were enrolled. Platelet reactivity (PR) was determined using Multiplate assays. Patients were grouped into quintiles based on their PR values. Upper and lower quintiles defined HPR and LPR, respectively, whereas quintiles 2–4 defined normal responders. All patients were assigned PREDICT score points in clinical categories (age?>?65, reduced left ventricular function, reduced kidney function, acute coronary syndrome (ACS) and diabetes). We found an association between the cumulative number of PREDICT score variables and the incidence of HPR for clopidogrel (HPR (ADP)) (p?p?=?0.007). In addition, the higher the PREDICT score, the higher the risk of HPR (ADP) (1–3 points, odds ratio (OR) 3.82 (95% CI 1.5–9.73, p?=?0.005); 4–6 points OR 4.11 (95% CI 1.61–10.52, p?=?0.003); 7–9 points OR 9.84 (95% CI 3.49–27.7, p?相似文献   

Effect of clopidogrel pretreatment on ischemic complications of percutaneous coronary intervention among bivalirudin-treated patients (from the EVENT registry)

Although clopidogrel pretreatment benefits patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes, these benefits are less well established among patients undergoing elective PCI--in particular, when they are treated with the direct thrombin inhibitor, bivalirudin. We used data from the multicenter Evaluation of Drug Eluting stents and ischemic Events registry to assess the association between clopidogrel pretreatment and PCI-related complications among patients undergoing elective PCI with bivalirudin as the antithrombotic regimen. The primary end point was the composite of in-hospital death or myocardial infarction. From January 2005 and December 2007, 4,681 patients underwent elective PCI at 55 United States centers, and 1,913 (41%) received bivalirudin as the planned anticoagulant. Clopidogrel pretreatment was used in 923 patients (48%). The incidence of in-hospital death or myocardial infarction was similar among patients who did and did not receive clopidogrel pretreatment (5.5% vs 5.8%, p = 0.83). This result was unchanged in propensity-adjusted analyses (adjusted odds ratio for pretreatment 0.91, 95% confidence interval 0.60 to 1.39, p = 0.66). Also, no differences were seen in the in-hospital bleeding events (1.0% vs 1.0%, p = 0.94) or 1-year ischemic complications between the 2 treatment groups (7.5% vs 8.3%, p = 0.26). In conclusion, among unselected patients undergoing elective PCI with bivalirudin as the planned anticoagulant, clopidogrel pretreatment was common but was not associated with a reduced risk of ischemic complications.     

Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin

We hypothesized that direct thrombin inhibition could attenuate platelet activation and release of soluble CD40 ligand (sCD40L), a marker of inflammation, during percutaneous coronary intervention (PCI). To assess platelet function under flow conditions with bivalirudin versus unfractionated heparin (UFH), we employed the cone and plate(let) analyzer (CPA) assay in drug-spiked blood samples from volunteers (n = 3) in vitro, and then in PCI patients who received bivalirudin alone (n = 20), UFH alone (n = 15), and clopidogrel pretreatment plus bivalirudin (n = 15). Scanning electron microscopy was employed to image bivalirudin or UFH-treated platelets to determine whether platelet function observations had a morphologic explanation. Enzyme immunoassay was used to measure sCD40L levels in PCI patients. In vitro, bivalirudin decreased platelet surface coverage; UFH increased platelet surface coverage. In PCI patients, bivalirudin alone decreased platelet surface coverage, UFH alone increased platelet surface coverage, and clopidogrel pretreatment plus bivalirudin additively reduced platelet surface coverage. Unlike UFH, bivalirudin did not activate platelets in SEM studies. Bivalirudin alone or coupled with clopidogrel significantly reduced plasma sCD40L in PCI patients. In conclusion, our findings suggest that under flow conditions, bivalirudin alone or coupled with clopidogrel may have an antiplatelet effect versus UFH alone during PCI. These data suggest that bivalirudin and UFH may confer an anti-inflammatory effect by reducing sCD40L during PCI.     

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.     

High-dose atorvastatin pretreatment could diminishes microvascular impairment in patients undergoing elective percutaneous coronary intervention

Objectives High-dose statins pretreatment is reasonable before percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial injury. However, the mechanism underlying this protective effect has not been elucidated. The aim of this study is to evaluate the effects of high-dose atorvastatin pretreatment on microvascular function and myocardial injury after elective PCI. Methods Eighty four patients underwent elective PCI were randomly assigned to high-dose atorvastatin (40 mg/d) and low-dose atorvastatin (20 mg/d) treatment for 7 days before PCI. The index of microcirculatory resistance (IMR) was measured by an intracoronary ressure/temperature sensor-tipped guidewire at maximal hyperemia after PCI. Fractional flow reserve (FFR) was measured before and after procedure. Troponin I levels were obtained at baseline and 20–24 h after procedure. Results IMR values were significantly lower in high-dose group when compared to low-dose group (16.5 ± 6.1 vs. 31.2 ± 16.0, P < 0.001). Pre-PCI troponin I levels between the two groups were similar (0.028 ± 0.05 vs. 0.022 ± 0.04, P = 0.55). However, post-PCI troponin I levels in high-dose group were significantly lower than low-dose group (0.11 ± 0.02 vs. 0.16 ± 0.09, P < 0.001). Multivariate analysis identified maximum inflation pressure > 20 atm as an independent predictor of IMR > 32 (Odds ratio (OR): 3.3, 95% confidence intervals (95%CI): 1.3–8.5, P = 0.02). High-dose atorvastatin was the only independent protective factor of IMR > 32 (OR: 0.29, 95%CI: 0.11–0.74, P = 0.01). Conclusions The present study confirmed that diminishing microvascular impairment is one of the mechanism underlying protecting effect of high-dose statins pretreatment from myocardial injury during PCI. These suggest that high-dose statin pretreatment is reasonable in patients undergoing elective PCI.     

600 mg负荷量氯吡格雷对直接经皮冠状动脉介入患者心肌灌注的影响

目的 探讨600mg负荷量氯吡格雷对直接经皮冠状动脉介入（PCI）患者心肌灌注的影响.方法 将接受直接PCI的急性ST段抬高型心肌梗死（STEMI）患者86例,根据氯吡格雷负荷量随机分为300 mg负荷量组（43例）和600 mg负荷量组（43例）,比较两组患者的基础资料,PCI术前、术后12 h、术后24 h PIGF、hs-CRP水平,sumSTR≥50％和MBG 2/3分级在两组中的比例,以及住院期间严重不良心脏事件（MACE）发生率等,评价600 mg氯吡格雷对行直接PCI的STEMI患者心肌灌注的影响.结果 ①600 mg负荷量组中sumSTR≥50％和MBG 2/3级的比例明显高于300 mg负荷量组,差异有统计学意义（P＜0.05）.②两组相比,PCI前和PCI后12 h 600 mg负荷量组PIGF和hs-CRP水平差异无统计学意义（P＞0.05）,而术后24 h PIGF和hs-CRP水平差异有统计学意义（P＜0.05）.③两组间心脏不良事件、出血等事件发生率比较差异无统计学意义（P＞0.05）.结论 STEMI行直接PCI患者给予600 mg负荷量氯吡格雷比300 mg负荷量更能改善心肌组织的灌注.