| Backgroud Percutaneous coronary intervention (PCI) is a usefulexamination method for patients with stable angina. During PCI, the bloodsupply to the opened lesions of vessels may cause a ruptured coronaryplaque, thrombosis, and damage to vascular endothelial structure andfunction. Earlier studies suggested that statins have pleiotropic effects，which are independent of their lipid-lowering properties, includingimprovements in nitric oxide bio-availability and endothelial function,anti-inflammatory activity, plaque stability, and anticoagulant activity. Inthe NAPLES II trial, patients were administered80mg of atorvastatin priorto undergoing PCI. The administration of atorvastatin significantly reducedthe incidence of MACE within30days; however, the beneficial outcomes inpatients with stable angina who underwent long-term statin therapy could beattributed to a reduction in the inflammatory response and platelet activation.The ARMYDA trials showed that short-term statin therapy canprotect myocardial tissue before PCI. The ARMYDA-CAMS trialconfirmed that short-term statin use before PCI significantly reducedplasma-E and vascular cell adhesion molecule1levels, thereby improvingendothelial function.However, the beneficial effects of chronic statin pre-treatment haslimitation in its applicability, whereas the acute effects of high-dose statinmay be more clinically relevant in the patients with stable angina. Therefore,we conducted a prospective randomized trial to evaluate whether a singleloading dose of80mg atorvastatin could affect the levels of inflammation,platelet activation, and incidence of major adverse cardiac events (MACE)within30days in patients with stable angina who received long-term statintherapy.PCI triggered increased coronary inflammation and platelet activation,thereby increasing the risk of stenosis. Simvastatin reduces plateletactivation in patients with ACS; however, the effect of high-dose statinpretreatment on the level of platelet activation is not completely understood,as very few studies have been conducted. Thus, we found that intensiveatorvastatin pretreatment reduced platelet activation in patients with stableangina who underwent long-term statin therapy.Objective This study was designed to investigate whether high-doseatorvastatin before PCI can reduce inflammation, platelet activation, and MACE in patients with stable angina who are undergoing long-term statintherapy.Methods The study population consisted of150patients with stableangina who were admitted to the second affiliated hospital of ChongqingMedical University and who underwent PCI from January2010to July2011.All patients had received long-term regular statin therapy for at least1monthbefore the procedure. The inclusion criteria were acute coronary syndrome(ACS), severe liver and kidney disease, heart failure, cancer, and pregnancy.The study was reviewed and approved by the hospital ethics committee. Allpatients provided written consent.Hypertension was defined as a systolicblood pressure of at least140mmHg and/or a diastolic blood pressure of atleast90mmHg. Type2diabetes mellitus was diagnosed using AmericanDiabetes Association criteria. Kidney disease was defined by an elevatedserum creatinine level of≥133u mol/L.Of the150patients,35patients refused to participate in the study.Eligible patients (n=115) were randomized to receive80or20mg ofatorvastatin. Patients were assigned in a1:1ratio with a computer-generatedrandomization sequence. After coronary angiography, the remaining115patients (80-mg atorvastatin arm, n=56;20-mg atorvastatin arm, n=59)were enrolled in the study.Physicians performing the procedure and the follow-up assessmentswere blinded to the randomization assignment. The patients were pre-treated before primary PCI with chewable aspirin (300mg) and clopidogrel(300-mg loading dose). All PCIs were performed by experiencedinterventional cardiologists through a femoral approach using a7Fr guidingcatheter. After PCI, aspirin (100mg/day) was continued indefinitely, andclopidogrel (75mg/day) was administered for at least1month. Afterintervention, all patients were treated with the usual maintenance dose ofatorvastatin (20mg/day), irrespective of the initial randomizationassignment. The subjects were advised to rest and to consume a low-fat dietwith statin, aspirin, beta-blockers, and angiotensin converting enzymeinhibitors. Serum levels of interleukin-6, high-sensitivity C-reactive protein,tumor necrosis factor-α, GMP-140, and p-selectin were measured24hbefore and after PCI. The30-day incidence of MACE was determined.Blood was drawn from an antecubital vein at24h pre-and post-PCI.Plasma was isolated and stored at-80°C before analysis. Interleukin-6(IL-6)and tumor necrosis factor-α (TNF-α) were assessed using chemiluminescentimmunoassay techniques (Access2Automatic Analyzer; Beckman,Fullerton, CA, USA) and radioimmunoassay (Shanghai Yanyu Chemical Co.,Shanghai, China), respectively. Serum glucose, total cholesterol,low-density lipoprotein cholesterol, high-density lipoprotein cholesterol,triglycerides, and high-sensitivity C-reactive protein (hs-CRP) were alsoassessed (HITACHI912Analyzer; Roche Diagnostics, Mannheim,Germany). GMP-140was determined using an enzyme-linked immunosorbentassay kit (R&D Systems, Minneapolis, MN, USA). P-selectin (CD62P) wasmeasured by flow cytometry (ELITE; Beckman). CD62P-FITC, CD61-PE,and the same type control for IgG1-FITC/IgG1-PE were provided by SantaCruz Biotechnology (Santa Cruz, CA, USA). The normal reference valueranged between2and5%.All patients were followed closely in a special outpatient clinic or bytelephone for about30days after discharge. MACE, including relapseangina, myocardial infarction, cardiac death, and stent thrombosis ortarget-vessel revascularization by either PCI or coronary artery bypassgrafting were recorded. MACE were diagnosed with typical clinicalperformance and laboratory examinations such as electrocardiograms andmyocardial enzymes. All MACE were reviewed by two experiencedcardiologists who were blinded to the angiographic data.Continuous variables are expressed as the mean±standard deviation,and categorical variables are expressed as percentages. Comparisons weremade by matching t-tests in each group and t-tests between the groups.Categorical variables were compared using chi-square tests. All variableswith P-values <0.05in a univariate analysis (age, hypertension, currentsmoking, diabetes mellitus, statin pretreatment, and stenting) were includedin the model. A P-value <0.05was considered significant. SPSS version13.0(Chicago, IL, USA) was used for all statistical analyses. Results No significant differences were observed in the baselineclinical and procedural characteristics, including mean age, sex ratio, stentplacement, or coronary risk profiles such as diabetes mellitus, smoking,hypertension, and hyperlipidemia, between the two groups (P>0.05). Nosignificant differences in level were observed between the two groups forinflammation and platelet activation before PCI. The levels of inflammationand platelet activation were significantly lower after24h in the group thatreceived intensive statin therapy (P <0.05). The levels of inflammation andplatelet activation increased sharply24h after PCI in the group that receivedthe lower dose of atorvastatin (P>0.05). In other words, pretreatment with ahigh dose of atorvastatin decreased the incidence of MACE sharply within30days (P <0.05).Our study has several limitations. The sample size was small, andpatients with non-specific symptoms such as chest pain required furtherinvestigation. We could not determine the clinical outcome according to thedose of statin or the exact duration of therapy given the small sample size.Thus, a large registry study is needed to generalize our results.Conclusions Pretreatment with a high dose of atorvastatin significantlyreduced inflammation, platelet activation, and the incidence of MACE inpatients with stable angina. |
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