Overcoming Aspirin Resistance with Loading Clopidogrel Earlier in Elective Percutaneous Coronary Intervention

We aimed to analyze the clinical effect of clopidogrel loading time on adverse cardiovascular events among patients with aspirin resistance. Recurrent adverse events may still occur despite dual antiplatelet therapy after coronary stenting. Aspirin resistance is one of the possible reasons of this trouble. Optimal antiplatelet strategy for coronary stenting is unknown among patients with aspirin resistance. A total of 980 patients scheduled for elective coronary stenting were enrolled and allocated into two groups according to the loading time of clopidogrel more or less than 6 hours before coronary intervention (early- or late-loaded groups, respectively). Aspirin resistance was determined according to the urinary levels of 11-dehydrothromboxane B2. Overall 240 patients who were allocated to early- and late-loaded groups were identified as aspirin resistant according to the urinary levels of 11-dehydrothromboxane B2. After a follow-up period of 12 months major adverse cardiac events were observed among 16 patients (13.9%) in the early-loaded group and 30 patients (25.8%) in the late-loaded group (p = 0.02). Early loading of clopidogrel was an independent predictor of lower rate of cardiac events (hazard ratio = 0.46 [0.32–0.76, 95% confidence interval], p = 0.001). The rates of bleeding events and periprocedural myocardial infarction were similar in early- and late-loaded groups. The current study demonstrated that loading of clopidogrel earlier than 6 hours before elective coronary stenting among aspirin-resistant patients was associated with increased benefits for ischemic events with similar bleeding rates.     

Cardiac Preconditioning during Percutaneous Coronary Interventions

Ischemic preconditioning (PC) is a polygenic defensive cellular adaptive phenomenon of the heart to ischemic stress, whereby the heart changes its phenotype to become more resistant to subsequent ischemia. Early and late of PC represent two chronologically and pathophysiologically distinct phases of this phenomenon, which can be recruited pharmacologically. We represent a post hoc analysis examining the late PC-mimetic effects of nitroglycerin (NTG) on peri-procedural myocardial necrosis during percutaneous coronary intervention (PCI). A group of 66 patients presenting with angina were randomized, 24 h prior to a scheduled PCI for single obstructive CAD, to a 4 h pretreatment with intravenous NTG or saline. Measurements of electrocardiographic ST-segment shifts, echocardiographic regional wall motion and angina scores demonstrated that NTG pre-treatment preconditioned the heart by rendering it resistant to ischemia during balloon inflations. NTG-pretreated patients exhibited trends towards lower average peak CK (131.1 vs. 188.6 U/L, P = 0.38) and CK-MB levels (7.1 vs. 12.6 ng/ml, P = 0.40). NTG, however, had no significant impact on the incidence of post-procedural MI or any cardiac enzyme elevation. The exploitation of ischemic and pharmacological PC may prove a useful strategy to confer cardioprotection during high-risk PCI and is worth exploring.     

Increase of Initial Success and Safety of Single-Vessel Percutaneous Transluminal Coronary Angioplasty in 1371 Patients: A Seven-Year Experience

Three successive time periods were compared to study the impact of evolving techniques and new equipment on the immediate results of single-vessel percutaneous transluminal coronary angioplasty (PTCA), the initial success rate and major complication rate (death, myocardial infarction, and urgent surgery). The three periods were selected on the basis of a significant advance in either PTCA technique or equipment. In period I from 1980 to 1983 a nonsteerable catheter system was used. In period II from 1983 to 1986 a steer-able catheter was used. In period HI from 1986 to 1987 the long guidewire technique and/or monorail system was used. A total of 1,371 successive patients underwent single-vessel dilatation for stable angina (848 patients) or for unstable angina (523 patients). Initial success was defined as a reduction of the stenosis to less than 50% with no major complications (myocardial infarction or death, or the necessity of proceeding to coronary artery bypass surgery). The initial success rate increased from 68% (period I) to 88% (period II) and to 91% (period III) for all attempts. When attempts of dilatation of totally occluded vessels were excluded these figures were 71%, 91%, and 95%, respectively. The overall major complication rate decreased from 16% (period I) to 8% (period II) to 3.5% (period III). Thus, increase in investigator experience, technical improvements of balloon catheter systems, and introduction of new PTCA techniques have resulted in an increase in success and safety of PTCA procedures. (J Inter-ven Cardiol 1988:1:1)     

平均血小板体积与血小板体积分布宽度联合对稳定性冠状动脉疾病远期预后的价值

目的:评估入院时平均血小板体积(MPV)及血小板体积分布宽度(PDW)联合对接受择期经皮冠状动脉介入治疗(PCI)的稳定性冠状动脉疾病患者远期预后的预测价值。方法:本研究共纳入4293例患者,根据MPV及PDW的中位数,将患者分为3组:低(MPV+PDW)组(n=2019);MPV+PDW异常组(即高MPV+低PDW或低MPV+高PDW,简称MPV+PDW异常组,n=333);高(MPV+PDW)组(n=1941)。应用多因素Cox回归分析比较不同组别与远期预后的相关性。结果:基线资料分析表明,与低(MPV+PDW)组患者相比,高(MPV+PDW)组患者合并糖尿病者更多,左心室射血分数(LVEF)和估算肾小球滤过率(eGFR)更低,糖化血红蛋白更高,使用β受体阻滞剂比例更低(P均<0.05)。与低(MPV+PDW)组比较,高(MPV+PDW)组患者心原性死亡率更高[17(0.9%)vs 5(0.2%),P=0.021],全因死亡发生率有升高趋势,但差异无统计学意义[25(1.3%)vs 16(0.8%),P=0.298]。Kaplan-Meier分析表明,高(MPV+PDW)组患者心原性死亡发生率显著高于其他组别(log-rank P=0.022)。多因素Cox回归分析表明,接受PCI的稳定性冠状动脉疾病患者中,高(MPV+PDW)组患者的2年心原性死亡的发生风险显著高于低(MPV+PDW)组患者(HR=3.497,95%CI:1.155~10.586,P=0.027)。结论:在接受择期PCI的稳定性冠状动脉疾病患者中,高MPV高PDW与远期预后不良相关。     

Comparison of Cilostazol and Ticlopidine for One-Month Effectiveness and Safety after Elective Coronary Stenting

PURPOSE: To compare the oral antiplatelets, phosphodiesterase III inhibitor cilostazol and the thienopyridine ticlopidine, for one-month effectiveness and safety as an adjunctive therapy after coronary stenting. METHODS: Published studies retrieved through Medline and other databases from 1966-2002. Meta-analyses evaluated effectiveness and adverse side effects for one-month administrations of aspirin plus cilostazol or aspirin plus ticlopidine therapy after coronary stenting. Major adverse cardiac events (MACE), stent-associated thrombosis or adverse side effects after coronary stenting were compared between the two study arms and expressed with the odds ratios (OR) specific for the individual studies and meta-analytic summary for OR. RESULTS: Five clinical studies met the inclusion criteria, and 4 of these studies underwent meta-analysis. With regard to the comparison of the OR summary for MACE and stent-associated thrombosis for the clinical outcome, there were no statistical significant differences between aspirin plus cilostazol and aspirin plus ticlopidine. While, the incidence of adverse side effects tended to be lower, they were not statistically significant in patients with aspirin plus cilostazol. CONCLUSIONS: Our meta-analysis results indicated that there were no differences between cilostazol (plus aspirin) and ticlopidine (plus aspirin) with regard to effectiveness and safety for a one-month period when used as an adjunctive therapy after coronary stenting.     

Drip and Ship: A New Strategy for the Treatment of Acute Coronary Syndromes

Glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway of platelet aggregation by preventing fibrinogen from binding to the GP IIb/IIIa platelet receptor. In patients with unstable angina (UA) or a non–Q wave myocardial infarction (NQWMI), including those with UA refractory to medical therapy, these agents decrease the risk of death, myocardial infarction (MI), and recurrent ischemia. Most patients with acute coronary syndromes are managed in hospitals without on-site angioplasty capabilities and often require transfer for an interventional procedure. We propose that GP IIb/IIIa inhibitors can be safely initiated at the referring hospital. We studied 20 patients with UA/NQWMI in whom therapy with a GP IIb/IIIa inhibitor, in addition to standard medical therapy, was initiated prior to transfer for an urgent percutaneous coronary intervention (PCI) (drip and ship). The primary end point was a composite of death, MI, and recurrent ischemia at 30 days. Twelve patients were treated with abciximab, 5 patients were treated with tirofiban, and 3 patients initially treated with tirofiban were converted to abciximab. Procedural success occurred in 33 out of 36 (92%) lesions and 18 out of 20 (90%) patients. At 30 days, 4 out of 20 (20%) patients had recurrent ischemia. The PTCA sites were widely patent in the 3 patients who underwent repeat angiography. The fourth patient had an unsuccessful PCI and was referred for coronary artery bypass surgery. There were no MIs or deaths. Patients who require transfer for an urgent PCI can be managed safely and efficaciously by initiating a GP IIb/IIIa inhibitor, in addition to standard medical therapy, prior to transfer.     

Platelet Function and Myocardial Injury During Percutaneous Coronary Intervention

Background: Several studies have shown that inhibition of the glycoprotein IIb/IIIa receptor can reduce myocardial injury during percutaneous coronary intervention (PCI). The present study was performed to investigate platelet function, using a bedside diagnostic system, to test the hypothesis that patients with activated platelets have an increased risk for myocardial injury during PCI. Such information would be valuable to guide the PCI operator to whom he or she should give a glycoprotein IIb/IIIa inhibitor during and after the procedure. Methods: 155 consecutive patients undergoing PCI were included in the study. 94 of the patients had stable angina pectoris and the remaining patients had unstable angina pectoris or ongoing myocardial infarction. Troponin T levels were measured in serum before PCI and at 6 am the day after PCI by an immunoassay. Platelet function was analyzed in arterial blood before PCI using the platelet function analyzer PFA-100® by Dade Behring. Results: The platelet function analyzer PFA-100® could not discriminate between patients with or without myocardial injury during the procedure but between patients with or without acetyl salicylic acid. Conclusion: The platelet function analyzer PFA-100® cannot be used to guide the PCI operator to whom he or she should give a glycoprotein IIb/IIIa inhibitor but the results indicate that PFA-100® can be used to monitor platelet effects of ASA therapy.     

Clinical Application of Procedural Platelet Monitoring during Percutaneous Coronary Intervention among Patients at Increased Bleeding Risk

The goal of platelet function testing in the catheterization laboratory is to provide information about the platelet contributions to the risk of thrombotic or hemorrhagic events and optimization of anti-platelet therapy for percutaneous interventions. We present several illustrative cases in which platelet monitoring with the Rapid Platelet Function Assay (RPFA^TM, Accumetrics) was used to guide dosing of a glycoprotein (GP) IIb/IIIa inhibitor for coronary and peripheral intervention among patients at increased bleeding risk.     

血小板膜GPⅡb/Ⅲa基因多态性与冠心病

血小板膜GPⅡb/Ⅲa的基因多态性能够通过影响血小板的功能,进而在冠心病的发病以及治疗中的阿司匹林抵抗、二磷酸腺苷受体拮抗剂疗法中发挥作用。但它是否为冠心病独立的危险因子尚有争议,2者之间的关系以及机制的阐明将有可能为冠心病的防治提供崭新的思路与策略。     

Coronary stenting with the half (disarticulated) Palmaz-Schatz stent: Immediate results and six-month follow-up

Coronary stenting with the half disarticulated Palmaz-Schatz stent is particularly suitable for ostial stenoses, diaphragm stenoses, stenoses distal to tortuous segments or coronary bends and localized dissections after balloon angioplasty. Nevertheless very few data regarding the half stent exist and follow-up data are nonexistent. From January of 1994 to December of 1995 a total of 207 half stents were implanted in 175 patients. Most patients had stable or unstable angina and in the majority of cases the stent was implanted due to localized dissection or to suboptimal result. The procedural success rate was 98%. After stent implantation, 82 patients were treated with acetylsalicylic acid (ASA) and oral anticoagulant (group A), whereas 93 were treated with ASA and ticlopidine (group B). Seven patients had subacute thrombosis (5, group A; 2, group B), and six patients had major bleeding (5, group A; 1, group B). Overall, patients in group A had more cardiovascular complications than patients in group B (10, group A; 3, group B; p = 0.047). After 6-mo follow-up, 1 patient had died and 27 patients had symptoms of angina (16%). Thirteen patients underwent a second PTCA (7%) and four patients (2%) were referred for coronary artery bypass. In conclusion, coronary stenting with half Palmaz-Schatz stent appears to be a safe and effective procedure. In selected cases, the half Palmaz-Schatz stent is easier to handle than the complete stent, it is associated with a low rate of clinical restenosis, and it lowers procedural costs. Cathet. Cardiovasc. Diagn. 41:371–376, 1997. © 1997 Wiley-Liss, Inc.     

Aspirin Treatment and Outcomes After Percutaneous Coronary Intervention : Results of the ISAR-ASPI Registry

Background

Aspirin administration, as part of a dual antiplatelet treatment regimen, is essential for patients undergoing percutaneous coronary intervention (PCI). Although the correlation between high on-clopidogrel treatment platelet reactivity (HCPR) and clinical outcome is well established, data for high on-aspirin treatment platelet reactivity (HAPR) are conflicting.

Objectives

The aim of the ISAR-ASPI (Intracoronary Stenting and Antithrombotic Regimen—ASpirin and Platelet Inhibition) registry was to assess the value of HAPR as a possible prognostic biomarker in PCI-treated patients with regard to clinical outcome.

Methods

From February 2007 to May 2013, we identified 7,090 consecutive PCI-treated patients with measured on-aspirin treatment platelet aggregation values directly before PCI. Platelet function was assessed with a Multiplate analyzer. The primary endpoint was death or stent thrombosis (ST) at 1 year.

Results

The upper quintile of patients (n = 1,414), according to Multiplate measurements, was defined as the HAPR cohort. Compared with non-HAPR patients (n = 5,676), HAPR patients showed a significantly higher risk of death or ST at 1 year (6.2% vs. 3.7%, respectively; odds ratio [OR]: 1.78; 95% confidence interval [CI]: 1.39 to 2.27; p < 0.0001). HAPR was found to be an independent predictor of the primary outcome (adjusted hazard ratio [HR_adj]: 1.46; 95% CI: 1.12 to 1.89; p = 0.005).

Conclusions

HAPR, measured at the time point of the PCI, is associated with a higher risk for death or ST during the first year after PCI. Present data are in support of the addition of HAPR to a panel of prognostic biomarkers in PCI-treated patients.     

Advances in Percutaneous Coronary Interventions for Elderly Patients

Coronary heart disease (CHD) is one of the leading causes of morbidity and the most common cause of death in older adults. Paradoxically, elderly patients tend to be systematically excluded from randomized-controlled cardiovascular trials, which complicates decision-making in this population. Management of CHD in the elderly is frequently more difficult in virtue of chronic comorbid conditions and aging-intrinsic dynamics. Despite these challenges, the number of elderly and very elderly patients undergoing percutaneous coronary interventions (PCI) is increasing. Elderly patients in many registries and large clinical series exhibit even a greater benefit from interventional procedures than younger patients, but they have a higher rate of overall complications. We present an overview of the current available evidence of PCI in older adults with stable and unstable CHD, including comparisons between drug-eluting and bare-metal stents, transfemoral and transradial access, and methods of revascularization. Adjuvant antiplatelet and antithrombotic therapies are also discussed.     

冠状动脉介入治疗术后局部缺血防治进展

经皮冠状动脉成形术(PTCA)术后局部缺血并发症包括:急性冠状动脉闭塞,发生率2%~10%,病人的死亡率随之增加。由于侧支闭塞或血栓形成,围手术期心肌梗塞发生率5%~20%。急性冠脉综合症、老年病人、复合病变患者、围手术期并发症大大增加,直接支架植入有效防治急性冠脉闭塞,但仍然存在血栓形成等并发症,合用阿司匹林和抗血小板因子(抵克力得、氯吡格雷、阿昔单抗、依替巴肽、替罗非班)能降低局部缺血的发生率,已成为PTCA病人标准的辅助治疗     

Aspirin and dipyridamole and their limitations in the therapy of coronary artery disease

We have reviewed some of the voluminous literature on the effects of aspirin combined with dipyridamole on coronary thrombosis. There is clear evidence that aspirin is partially effective in preventing platelet aggregation and subsequent thrombosis in experimental constricted and damaged coronary arteries of dogs. Clinical studies show a clear reduction in myocardial infarction in male human subjects who are given aspirin as therapy for unstable angina, or as prophylaxis in asymptomatic individuals. In many studies aspirin and dipyridamole have been combined and are effective. We have not found dipyridamole to be effective in the dog with coronary artery constriction and find no substantial evidence that it is effective in preventing myocardial infarction in man. Until definitive studies show that combining dipyridamole with aspirin is more effective than aspirin alone, we do not recommend its use for prevention of coronary thrombosis.