经皮冠状动脉介入治疗术前的负荷剂量他汀类药物治疗

急性冠状动脉综合征(ACS)患者采用经皮冠状动脉介入治疗(PCI)已经成为冠状动脉血运重建的最佳手段之一。ACS的发病与冠状动脉局部斑块病变不稳定和炎症反应有关。PCI本身可能会引起血管壁的损伤和炎症反应,进而引起心肌损伤。他汀类药物的调脂和抗炎症作用,为拓宽他汀类药物的临床应用提供了依据。近年来,在PCI围术期应用他汀类药物负荷剂量治疗受到重视,这种治疗策略应用于何种类型的冠心病更有价值,值得探讨。     

Statin treatment before percutaneous cononary intervention

Treatment with 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improves short-and-long term prognosis in high-risk patients with stable coronary artery disease and in those with acute coronary syndrome and their use is strongly recommended for secondary prevention.Moreover, recent data suggest that statin pre-treatment is associated with a better short- and long-term outcome in patients undergoing percutaneous coronary intervention. Current guidelines for coronary revascularization recommend the use of high-dose of statins before percutaneous coronary intervention to reduce the risk of periprocedural myocardial infarction in statin naïve patients (class IIa A) and in those on chronic statin therapy (class IIa B). However, the beneficial clinical effects elicited by statins in patients undergoing coronary angioplasty may arise not only from a cardiac protection against periprocedural myocardial injury but also from a renal protection against acute kidney injury caused by iodinated contrast media. Actually, statins exert multiple non-lipid lowering (pleiotropic) effects, including improved endothelial function, reduced inflammatory and immuno-modulatory processes, oxidative stress and platelet adhesion, that may contribute to both cardio- and nephro-protection even in the short-term.KEY WORDS : Statins, percutaneous coronary intervention, myocardial infarction, kidneyThe prognostic benefits of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in high-risk patients with stable coronary artery disease (CAD) and in those with acute coronary syndromes (ACS) are well established and their use is strongly recommended for secondary prevention (1-4). Two concepts arise from these studies about statin administration: earlier is better considering the time and higher is better considering the dose. In a cohort of 1,159 patients with acute myocardial infarction (MI), the statin treatment initiated within 48 hours after admission was associated with significantly lower major adverse cardiac events at one-year (17.8% vs. 24.6%; P=0.016) compared to statin treatment started after 48 hours; the early statin therapy was an independent predictor of one-year outcome [Odds Ratio (OR): 1.49; 95% Confidence Interval (CI): 1.0 to 2.21; P=0.045] (5). In patients with ACS, statin therapy may reduce one-month mortality (OR: 0.63; 95% CI: 0.41 to 0.99; P=0.047) when treatment is started very early, within 24 hours of hospitalization (6). The favourable effect of high-dose statin treatment is more evident in patients undergoing percutaneous coronary intervention (PCI). In the PROVE-IT TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) study, early intensive compared to moderate statin treatment, significantly reduced the composite end point of cardiovascular death, non fatal MI, recurrent ischemia or rehospitalisation for unstable angina in patients undergoing PCI [Hazar Ratio (HR): 0.73; 95% CI: 0.61 to 0.87; P=0.001] but not in those medically treated (HR: 0.84; 95% CI: 0.65 to 1.09; P=0.183), without a significant interaction between the dose of statin (intensive vs. moderate) and the treatment strategy (PCI vs. non PCI) (7). Few randomized studies have compared the prognostic impact of statin treatment when administered before PCI. However, available data suggest that pre-PCI statin administration may further improve prognosis. A recent meta-analysis of randomized trials that included stable CAD or ACS patients, showed a better 30-day outcome in the 1,649 patients randomized to short-term (from 12 hours to 2 weeks) high-dose statin compared to that of 1,649 patients randomized to low-dose or no statin therapy before PCI (8); in this meta-analysis, the rate of death, spontaneous non fatal MI or target vessel revascularization at 30-day was lower in patients pre-treated with statins (0.6% vs. 1.4%; OR: 44; 95% CI: 0.19 to 1.01; P=0.05). Moreover, non-ST elevation (NSTE) ACS statin-naïve patients (n=225) treated with high dose rosuvastatin (40 mg) 7-25 hours before PCI presented a better long-term outcome than patients (n=220) treated with rosuvastatin after intervention (Figure 1) (9). At 12 months, the composite primary end point of death, non-fatal MI, non-fatal stroke, or revascularization was significantly lower in the pre-PCI statin group (20.5% vs. 9.8%; P=0.002); similarly the risk of death and non-fatal MI at 12-month was significantly lower in patient who started rosuvastatin before PCI (HR: 3.71; 95% CI: 1.22 to 11.27; P=0.021) (9). Even a chronic statin therapy seems to improve long-term prognosis after PCI. Among 8,041 patients with stable CAD treated with PCI, 5,939 of these were on statin therapy (≥1 month) and 2,102 statin-naïve at the time of admission; statin therapy before PCI was associated with a significant reduction of one-year mortality (HR: 0.56; 95% CI: 0.42 to 0.75; P<0.001) with a benefit observed within the first month following PCI (10).Open in a separate windowFigure 1Clinical outcome during the follow-up. Incidence of death, non-fatal myocardial infarction, non-fatal stroke or revascularization at 1-month and at the end of 12-month follow-up in patients treated with high-dose rosuvastatin before percutaneous coronary intervention (statin) and in patients who received statin treatment after the procedure (control). From reference 9, modified.The beneficial clinical effects of statin pre-treatment may be related to their possible protective effects against both myocardial damage following PCI and kidney damage following contrast media administration. This review is focused on the relationship between the administration of statin therapy before PCI and the occurrence of periprocedural myocardial infarction (pMI) and contrast-induced acute kidney injury (CI-AKI).     

Statin administration before percutaneous coronary intervention: impact on periprocedural myocardial infarction.

AIMS: Peri-procedural non-Q-wave myocardial infarction is a frequent and prognostically important complication of percutaneous coronary intervention (PCI). It has been postulated that statins may reduce the rate of myocardial injury after PCI. METHODS AND RESULTS: Four hundred and fifty-one patients scheduled for elective PCI and not on statins were randomly assigned to either no treatment or to statin treatment. Statin administration was started at least 3 days before the procedure.Incidence of peri-procedural myocardial injury was assessed by analysis of creatinine kinase myocardial isoenzyme (CK-MB: upper limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (cTn I, ULN 0.10 ng/ml) before, 6 and 12 h after the intervention. A large non-Q-wave myocardial infarction was defined as a CK-MB elevation >5 times ULN alone or associated with chest pain or ST segment or T wave abnormalities. Median CK-MB peak after PCI was 1.70 (interquartile ranges 1.10-3.70) ng/ml in the Statin group and 2.20 (1.30-5.60) ng/ml in the Control group (p=0.015). Median peak of cTnI after PCI was 0.13 (0.05-0.45) ng/ml in the Statin group and 0.21 (0.06-0.85) ng/ml in the Control group (p=0.033). The incidence of a large non-Q-wave myocardial infarction was 8.0% in the Statin group and 15.6% in the Control group (p=0.012: OR=0.47; 95% CI=0.26-0.86). The incidence of cTnI elevation >5 times ULN was 23.5% in the Statin group and 32% in the Control group (p=0.043: OR=0.65; 95% CI=0.42-0.98). By logistic regression analysis, the independent predictors of CK-MB elevation >5 times ULN after PCI were intra-procedural angiographic complications (OR=9.36; 95% CI=3.06-28.64; p<0.001), statin pre-treatment (OR=0.33; 95% CI=0.13-0.86; p=0.023) and age >65 years (OR=2.58; 95% CI=1.09-6.11; p=0.031). CONCLUSIONS: Pre-procedural statin therapy reduces the incidence of large non-Q-wave myocardial infarction after PCI.     

他汀类药物在冠状动脉介入术前应用分析

目的分析冠状动脉介入（PCI）治疗前患者服用他汀类药物对预后状况的影响。方法选择116例行PCI治疗的病患,随机分组,Ⅰ组62例与Ⅱ组54例患者行相同治疗,Ⅰ组治疗前另行服用他汀类药物阿托伐他汀,治疗24周之后,观察两组患者出现MACCE（心脑血管事件）的情况及血液流变指数、血脂生化指标的变化状况,总结他汀类药物用于患者PCI治疗的价值。结果以他汀类药物配合PCI治疗的Ⅰ组患者MACCE总发生率为4．84％（3／62）,明显比Ⅱ组（24．07％）低,P〈0．05;且Ⅰ组术后的血液流变指标基本维持在正常范围,Ⅱ组均高于正常水平,Ⅰ组明显低于Ⅱ组;两组患者血脂生化指标均有所降低,Ⅰ组TC、TG、HDL—C降低比Ⅱ组显著,P〈0．05,LDL—C与Ⅱ组相比则降低不明显,P〈0．05。结论医师使用他汀类药物为行PCI的患者进行辅助治疗,可以有效降低MACCE发生率,控制血液流变及血脂生化指标,改善患者预后效果。     

Statin treatment and new-onset diabetes: A review of proposed mechanisms

New-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. To explain this association, three major mechanisms have been proposed and discussed in the literature. First, certain statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling. Other possible mechanisms implicated in the effect of statins on new-onset diabetes are: statin interference with intracellular insulin signal transduction pathways via inhibition of necessary phosphorylation events and reduction of small GTPase action; inhibition of adipocyte differentiation leading to decreased peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which are important pathways for glucose homeostasis; decreased leptin causing inhibition of β-cells proliferation and insulin secretion; and diminished adiponectin levels. Given that the magnitude of the risk of new-onset diabetes following statin use remains to be fully clarified and the well-established beneficial effect of statins in reducing cardiovascular risk, statins remain the first-choice treatment for prevention of CVD. Elucidation of the mechanisms underlying the development of diabetes in association with statin use may help identify novel preventative or therapeutic approaches to this problem and/or help design a new generation statin without such side-effects.     

Predictive factors of TIMI-3 flow before percutaneous coronary intervention in facilitated percutaneous coronary intervention for acute myocardial infarction

The outcome for facilitated percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is known to be more favorable in cases in which TIMI-3 flow is obtained before PCI. We investigated factors that affect the acquisition of TIMI-3 flow before PCI. Facilitated PCI was performed on 178 patients divided into two groups, a group in which TIMI-3 flow was acquired before conducting PCI and another in which it was not, and their background factors and short-term outcomes were investigated. The hemoglobin concentrations, white blood cell (WBC) counts, and HbA1c values were significantly lower in the group in which TIMI-3 flow was acquired before PCI and significantly more had a history of past smoking. According to the results of logistic analysis, WBC count (odds ratio [OR], 0.865, P = 0.0077), hemoglobin concentration (OR, 0.77, P = 0.0257), and smoking history (OR, 0.266, P = 0.0021) were independent factors that predicted acquisition of TIMI-3 flow. The WBC count and hemoglobin value on arrival at the emergency room and history of smoking were shown to be independent factors for acquisition of TIMI-3 flow before PCI in facilitated PCI.     

Clopidogrel treatment before percutaneous coronary intervention reduces adverse cardiac events

OBJECTIVE: Platelet inhibition during percutaneous coronary intervention (PCI) generally reduces adverse cardiac events. There are very few data on the combination of aspirin and the platelet adenosine diphosphate-receptor inhibitor clopidogrel given before the intervention. DESIGN: In a non-randomized comparison, a total of 706 consecutive patients received clopidogrel 375 mg in addition to aspirin on the day before PCI. The control group consisted of 724 consecutive PCI patients receiving only aspirin pre-treatment. RESULTS: The two groups were well balanced regarding baseline characteristics. Pre-treatment with clopidogrel reduced the in-hospital composite of death, myocardial infarction or urgent revascularization by 41% compared to the control (8.2% versus 4.8%, respectively; p = 0.010). This was due to a decreased incidence of myocardial infarction (7.2% versus 4.4%; p = 0.024) and percutaneous reintervention (1.2% versus 0.3%; p = 0.039). There was no difference in femoral complications between the groups. For every patient in the clopidogrel group, there was a cost reduction of SEK 447 ($40 United States currency). CONCLUSION: Clopidogrel treatment in addition to aspirin before PCI was associated with a reduction of in-hospital adverse cardiac events. It was also safe and cost-saving.     

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.     

CD62P分子在经皮冠状动脉介入术前后的表达变化

目的：研究CD62P在急性心肌梗塞（AMI）患者行经皮冠状动脉介入（PCI）术前和手术后即刻的表达变化。方法：60例AMI患者行PCI干预治疗,分别检测患者术前、术后即刻的血清和血小板膜CD62P分子的表达。结果：PCI术后即刻组血清CD62P表达明显低于手术前[（42.68±2.35）ng/ml∶（45.82±3.66）ng/ml,P〈0.05];术后即刻组血小板膜CD62P表达明显低于术前[（13.82±4.85）ng/ml∶（17.83±7.67）ng/ml,P〈0.05]。结论：经皮冠状动脉介入术后血清和血小板膜CD62P表达均较术前明显下降,提示及时和有效地恢复心肌血液供应能减轻急性冠脉综合征的炎症反应。     

冠状动脉介入术前高负荷量氯吡格雷预治疗的近期疗效

目的:对比观察拟行冠状动脉(冠脉)介入术患者术前服用高负荷剂量氯吡格雷600 mg与常规负荷剂量300 mg预治疗的有效性及安全性.方法:选取100例拟行冠脉介入术的患者,术前随机分别给予600 mg(50例)或300 mg(50例)负荷剂量氯吡格雷预治疗.分别检测2组服药前、服药后16、36 h二磷酸腺苷(ADP)诱导的血小板最大凝集率(MPAR),随访术后30 d和6个月主要临床心血管事件(包括死亡、心肌梗死、紧急靶血管血运重建、脑卒中等)和出血事件的发生情况.结果:服药后16 h,氯吡格雷600 mg组较之300 mg组对ADP(5μmol/L和20μmol/L)诱导的MPAR产生更大的抑制作用[ADP 5μmol/L,(21.83±18.04)%:(14.79±9.18)%,P＜0.05];[ADP 20μmol/L,(22.12±14.81)%:(15.67±10.15)%,P＜0.05)].而服药后36 h,2组ADP(5μmol/L和20μmol/L)诱导的MPAR率分别降低[ADP5μmol/L.(16.70±15.42)%:(12.94±10.34)%,P＞0·05]和[20μmol/L :(14.14±13.16)%:(10.19±9.49)%,P＞0.05].氯吡格雷600 mg组30d和6个月主要临床心血管事件发生率较300 mg组显著减少(P＜0.05,P＜0.01).2组30 d和6个月出血事件差异均无统计学意义.结论:冠脉介入术患者术前服用高负荷剂量氯吡格雷600 mg较之常规负荷剂量300 mg预治疗能更大程度抑制血小板凝集.同时可显著改善临床预后.     

冠心病患者经皮冠状动脉介入治疗术前后心电图缺血性J波的观察

目的 探讨经皮冠状动脉(冠脉)介入治疗(PCI)对冠心病患者心电图缺血性J波的影响及临床意义,为临床提供无创检查指标起到预警作用.方法 选择经皮冠状动脉造影确诊并行PCI治疗的冠心病患者(冠心病组)162例,其中不稳定性心绞痛(心绞痛组)108例,急性心肌梗死(心梗组)54例.记录PCI术前、术后24h内的12导联体表心电图,分别测量各导联J波的振幅和时限,分析PCI术前、术后J波的发生率及参数变化.根据狭窄的冠脉分为2个冠脉狭窄组(前降支狭窄组和右冠脉或回旋支狭窄组),观察体表12导联心电图J波的形态比较及发生率.结果 (1)PCI 术前、术后J波发生率最高为Ⅱ、Ⅲ、aVF导联,冠心病组发生率分别为33.95％、22.84％、26.54％和30.86％、19.75％、23.46％,心绞痛组发生率分别为37.04％、27.78％、31.48％和35.19％、25.00％、27.78％;而心梗组PCI术前为V5、Ⅱ、aVF、Ⅲ、V3导联J波发生率较高,术后J波发生率为V5、Ⅱ、aVF、aVL、Ⅲ导联J波发生率较高(分别为33.33％、27.78％、16.67％、12.96％、11.11％和22.22％、22.22％、14.81％、12.96％、9.26％).(2)前降支狭窄组PCI术前J波在V5、V6导联为25.78％,右冠脉或回旋支狭窄组PCI术前J波在Ⅱ、Ⅲ、aVF导联为35.37％;术后两组均在Ⅱ、Ⅲ、aVF组发生率最高,分别为21.09％和35.37％.(3)全部冠心病组在PCI术前的J波以振幅0.08 mV和时限0.02s的例数最多,PCI术后J波振幅为0.02 mV和时限0.02s例数最多.(4)全部冠心病组PCI术前J波振幅和时限在Ⅱ、Ⅲ、aVF、V3、V4导联上均大于PCI术后,差异有统计学意义[中位数(四分位数间距P25,P75)为:Ⅱ导联振幅0.05(0.05,0.10) mV比0.02(0.02,0.05) mY,P=0.00,时限0.03(0.02,0.04)s比0.02(0.02,0.03)s,P=0.00;Ⅲ导联振幅0.05(0.05,0.10) mV比0.02(0.02,0.05) mV,P=0.00,时限0.02(0.02,0.03)s比0.02(0.01,0.02)s,P=0.00;aVF导联振幅0.05(0.05,0.10)mV比0.02(0.00,0.08)mV,P=0.00,时限0.02(0.02,0.03)s比0.02(0.00,0.02)s,P=0.00;V3导联振幅0.05(0.05,0.16)mV比0.05(0.00,0.05)mV,P=0.03,时限0.02(0.02,0.04)s比0.02(0.00,0.02)s,P=0.01;V4导联振幅0.06(0.04,0.12)mV比0.01 (0.00,0.07) mV,P=0.01,时限0.04(0.04,0.05)s比0.01(0.00,0.02)s,P=0.00].结论 冠心病组和心绞痛组PCI术前、术后J波在Ⅱ、Ⅲ、aVF导联的发生率最高,而心梗组在V5、Ⅱ、Ⅲ、aVF导联较高;前降支狭窄与右冠脉或回旋支狭窄组J波分别在V5、V6与Ⅱ、Ⅲ、aVF导联的发生率最高;PCI术后,J波振幅和时限均降低,说明PCI对冠心病缺血性J波有相对较好的影响.