Randomized comparison of cilostazol vs ticlopidine for antiplatelet therapy after coronary stenting.

BACKGROUND: Cilostazol and ticlopidine are commonly prescribed for prevention of thrombosis after coronary stenting, but few studies have compared them. METHODS AND RESULTS: In the present study 642 patients who underwent stenting were randomized to treatment either with cilostazol + aspirin (C group, 321 patients) or ticlopidine + aspirin (T group, 321 patients). Quantitative coronary angiography (QCA) was performed immediately after stenting and at the 6-month follow-up. Treatment was continued until follow-up angiography. Baseline patient characteristics did not differ significantly. With the exception of a higher rate of stenting in a venous graft in the C group, there were no differences in angiographic characteristics or stent type. Baseline QCA analysis of the reference diameter, minimal lumen diameter (MLD) showed no significant differences. Follow-up QCA analysis of the MLD showed no significant differences. There were also no differences in restenosis or target lesion revascularization rates, or in the incidence of adverse reactions. However, the rate of subacute thrombosis (SAT) was significantly higher in the C group than in the T group (2% vs 0.3%, p=0.02). CONCLUSION: In the present study there was a similar restenosis rate with cilostazol or ticlopidine, but the rate of SAT was significantly higher with cilostazol. There was no significant difference in adverse reactions.     

Comparison of cilostazol versus ticlopidine therapy after stent implantation.

The aim of this study was to evaluate the efficacy of cilostazol for prevention of stent thrombosis compared with ticlopidine. Cilostazol is a potent antiplatelet agent with less serious side effects. However, few data are available about the effect of cilostazol in preventing stent thrombosis after coronary stent implantation. Four hundred ninety patients selected for elective stent placement were randomized to receive aspirin plus ticlopidine (n = 243) or aspirin plus cilostazol (n = 247) for 1 month. Clinical and laboratory evaluations were performed at regular interval. There were no differences in baseline characteristics between the 2 groups. During the first 30 days after stent implantation, major cardiac events or adverse drug effects were similar between the 2 groups: ticlopidine (2.9%) vs cilostazol (1.6%) group, p = NS; stent thrombosis (0.4% vs 0.8%, p = NS, respectively), myocardial infarction (0.4% vs 0.8%, p = NS), severe leukopenia (1.2% vs 0%, p = NS), severe thrombocytopenia (0.4% vs 0%, p = NS), and cerebral hemorrhage (0.4% vs 0%, p = NS). Adverse effects led to drug withdrawal in 7 patients in the ticlopidine group (2.9%) and in 5 in the cilostazol group (2.0%). There was no death during the follow-up period. Thus, aspirin plus cilostazol may be an effective antithrombotic regimen with comparable results to aspirin plus ticlopidine after elective coronary stenting.     

西洛他唑与噻氯匹定预防冠心病支架置入术后冠状动脉再狭窄的效果对比

目的评价西洛他唑对冠状动脉支架术后再狭窄的影响。方法150例行冠状动脉支架术的患者随机分为西洛他唑组(试验组)和噻氯匹定组(对照组)。两组患者于术前48 h开始服用西洛他唑200 mg/d或噻氯匹定500 mg/d,西洛他唑组术后持续服药6个月,噻氯匹定组服药4周,并分别加用阿司匹林100 mg/d至术后6个月。出院后定期门诊随访,术后6个月复查冠状动脉造影。结果在随访中,试验组严重心脏事件发生率和严重药物副反应较对照组少。试验组和对照组在支架术后6个月造影中最小管径(2.24±1.16 mm比2.04±1.24 mm)、实际管径获得(2.73±0.45 mm比2.78±0.46 mm)、最终管径丢失(0.90±1.05 mm比1.06±1.14 mm)、丢失指数(0.34±0.40比0.38±0.40)和再狭窄率(28.0%比36.7%)差异均无统计学意义。结论西洛他唑在冠状动脉支架置入后预防急性或亚急性血栓并发症和降低晚期再狭窄率与噻氯匹定具有接近的作用,对于不能耐受噻氯匹定的患者,西洛他唑可以作为替代药物。     

Comparison of ticlopidine and cilostazol for the prevention of restenosis after percutaneous transluminal coronary angioplasty

Prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to be a significant problem. Recent controlled studies have demonstrated that cilostazol suppresses restenosis after PTCA. The effects of ticlopidine, another antiplatelet agent, were compared in terms of outcomes of patients randomized for treatment with the two drugs after PTCA. A total of 35 patients (47 lesions) were assigned prospectively and randomly to ticlopidine (17 patients, 24 lesions) and cilostazol (18 patients, 23 lesions) groups. Minimal luminal diameter (MLD) and percentage of stenosis to reference diameter were estimated before PTCA, just after the procedure and after 4 months follow-up. All patients underwent 4 months angiographic follow-up, at the end of which MLD was 2.03+/-0.71 mm in the ticlopidine group and 2.05+/-0.68 mm in the cilostazol group (p = 0.95), and the percentage of stenosis to reference diameter was 31.4+/-16.7% and 30.0+/-17.0%, respectively (p = 0.78). The restenosis rate was 12.5% in the ticlopidine group and 17.4% in the cilostazol group (p = 0.69), relatively low as compared to the 20% to 30% reported in previous studies. Adverse drug reactions during the follow-up period were observed in two of the ticlopidine group and none of the cilostazol group. We conclude that both ticlopidine and cilostazol are effective for the prevention of restenosis after PTCA, however the former may be associated with slight side effects.     

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after coronary stent implantation

Background

The combination of a thienopyridine and aspirin has become the standard of care after intracoronary stenting. Clopidogrel appears to be better tolerated than ticlopidine but may be associated with more adverse cardiac events. We assessed the tolerability and efficacy of 2 weeks of therapy with ticlopidine and aspirin in comparison to clopidogrel and aspirin after coronary stent implantation.

Methods

Patients with successful intracoronary stent implantation at our institution were randomly assigned, in addition to aspirin, to receive either ticlopidine or clopidogrel. Loading doses were administered immediately after the procedure, and the drugs were continued for 2 weeks.

Results

Three hundred seven patients were randomly assigned: 154 patients to clopidogrel and 153 to the ticlopidine group. The primary end point of early drug discontinuation occurred in 5 patients (3.3%) in the ticlopidine group and 1 patient (0.6%) in the clopidogrel group (P = .121). Within 30 days, thrombotic stent occlusion occurred in 1 patient (0.7%) in the ticlopidine group and 3 patients (1.9%) in the clopidogrel group (P = .623). A major adverse cardiac event occurred in 3 patients (∼1.9%; P = 1.00) in each group.

Conclusions

There was a nonsignificant trend to improved tolerability of a 2-week regimen of clopidogrel and aspirin when compared with ticlopidine and aspirin in patients undergoing intracoronary stent implantation. The combination of clopidogrel and aspirin results in a comparably low incidence of major adverse cardiac events when compared with ticlopidine and aspirin.     

Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting: a randomized comparison of ticlopidine and cilostazol.

BACKGROUND: A prospective randomized study compared the preventive effects of ticlopidine plus aspirin therapy versus cilostazol plus aspirin therapy on subacute thrombosis (SAT) and restenosis after coronary stenting. METHODS AND RESULTS: After successful stenting of 327 coronary lesions in 282 consecutive patients, the patients were randomized to receive ticlopidine (200 mg/day) or cilostazol (200 mg/day). Aspirin (81 mg/day) was administered concomitantly in both groups. SAT occurred in 1 patient in the ticlopidine group (0.7%) and in 8 patients in the cilostazol group (5.6%, p=0.037). Based on follow-up angiography, restenosis occurred in 30 patients (23.3%) in the ticlopidine group and 35 patients (26.9%) in the cilostazol group (NS). The late loss was significantly smaller in the cilostazol group than the ticlopidine group (1.08+/-0.95 mm vs 0.78+/-0.93 mm, respectively, p=0.037). No significant differences between the 2 groups were observed with respect to the rates of total death, non-fatal cardiovascular events, or bleeding complications. CONCLUSION: The ticlopidine group showed significantly less SAT after stenting compared with the cilostazol group. After 6 months of treatment, the inhibition of neointimal proliferation was greater in the cilostazol group than in the ticlopidine group, but the prevention of restenosis was not confirmed.     

Effect of statin therapy on restenosis after coronary stent implantation

The effect of statins on the development of restenosis and clinical outcome after coronary stent implantation was assessed in a retrospective analysis of 525 consecutive patients. Baseline clinical, angiographic, and procedural characteristics did not differ between 258 patients with and 267 patients without statin therapy. Statin therapy was associated with a significantly (p<0.04) improved survival free of myocardial infarction and a significant reduction in repeat target vessel revascularization procedures (27.9% vs. 36.7%, p<0.05) during 6-month follow-up. Minimal lumen diameter was significantly larger (1.98+/-0.88 vs. 1.78+/-0.88 mm, p = 0.01), late lumen loss was significantly less (0.64+/-0.8 vs. 0.8+/-0.8 mm, p = 0.032), and net gain significantly increased (1.2+/-0.88 vs. 0.98+/- 0.92 mm, p = 0. 009) in patients receiving statin therapy. Dichotomous angiographic restenosis (> or =50%) rates were significantly lower, with 25.4% in the statin group compared with 38% in the no-statin group (p<0.005). Multivariate analysis identified statin therapy (p = 0.005), minimal lumen diameter immediately after stenting (p = 0.02), and stent length (p = 0.02) as independent predictors for subsequent restenosis development. Thus, statin therapy is associated with reduced recurrence rates and improved clinical outcome after coronary stent implantation.     

Effects of cilostazol on angiographic restenosis after coronary stent placement

This study evaluates the impact of cilostazol on post-stenting restenosis. Cilostazol is a potent antiplatelet agent with antiproliferative properties. Few data are available about the effect of cilostazol on poststenting restenosis. Four hundred nine patients (494 lesions) who were scheduled for elective stenting were randomized to receive aspirin plus ticlopidine (group I, n = 201, 240 lesions) or aspirin plus cilostazol (group II, n = 208, 254 lesions), starting 2 days before stenting. Ticlopidine was given for 1 month and cilostazol for 6 months. Follow-up angiography was performed at 6 months, and clinical evaluation at regular intervals. Baseline characteristics were similar between the 2 groups. The procedural success rate was 99.6% in group I and 100% in group II. There were no cases of stent thrombosis after stenting. Angiographic follow-up was performed in 380 of the 494 eligible lesions and the angiographic restenosis rate was 27% in group I and 22.9% in group II (p = NS). However, diffuse type in-stent restenosis was more common in group I than in group II (54.2% vs 26.8%, respectively, p <0.05). In diabetic patients, the angiographic restenosis rate was 50% in group I and 21.7% in group II (p <0.05). Clinical events during follow-up did not differ between the 2 groups. In conclusion, aspirin plus cilostazol seems to be an effective antithrombotic regimen with comparable results to aspirin plus ticlopidine, but it does not reduce the overall angiographic restenosis rate after elective coronary stenting.     

Thienopyridine therapy influences late outcome after coronary stent implantation

Clinical significance of resistance to aspirin and thienopyridine therapy is poorly defined. The authors aimed to evaluate whether more effective antiplatelet therapy is associated with better outcome in patients on dual-antiplatelet treatment. Using optical aggregometer, maximal platelet aggregation values were measured with induction of adenosine diphosphate, collagen, and adrenaline 30 +/- 5 days after coronary stent implantation in 134 patients. Markers of platelet activation were also analyzed with fluorescent immunoassay in 57 patients. After 10 months of follow-up, 33 patients reached the composite endpoint of cardiovascular death, myocardial infarction, and revascularisation. Adenosine diphosphate-induced maximal aggregation values were in significant relationship with the development of major adverse cardiac events (P < .01). Level of soluble P-selectin proved to be an independent risk factor of adverse outcome (P < .05). As efficacy of thienopyridine therapy showed significant relation with clinical outcome, the authors conclude that interindividual variability in response to adenosine diphosphate-receptor antagonists may be of substantial clinical importance.     

Effect of cilostazol on restenosis after coronary angioplasty and stenting in comparison to conventional coronary artery stenting with ticlopidine

BACKGROUND: The role of antiplatelet therapy with ticlopidine plus aspirin in the prevention of subacute thrombosis after coronary artery stenting has been established. However, restenosis remains a major limitation in coronary artery stenting. METHODS: To compare the effect of cilostazol on restenosis after coronary angioplasty and stenting with that of ticlopidine after coronary artery stenting, 213 patients with 230 lesions who underwent successful coronary interventions were evaluated. Optimal results (residual stenosis less than 30%) were obtained by balloon angioplasty in 112 lesions, 64 lesions were treated with aspirin 81 mg/day (balloon-aspirin group) and 48 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (balloon-cilostazol group). Stent implantation was performed in the remaining 118 lesions; 55 lesions were treated with ticlopidine 200 mg/day and aspirin 243 mg/day (stent-ticlopidine group) and 63 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (stent-cilostazol group). Concomitant medications were continued for 4 to 6 months of follow-up. RESULTS: No adverse events including acute occlusion and subacute thrombosis occurred in any groups. Although immediate gain and minimal lumen diameter immediately after angioplasty were significantly larger in stent groups than those in balloon groups, net gain at follow-up was significantly larger in cilostazol groups (1.54+/-0.83 mm in balloon-cilostazol group and 1.65+/-0.78 mm in stent-cilostazol group) than other groups (1.02+/-0.81 mm in balloon-aspirin group and 1.21+/-0.70 in stent-ticlopidine group) as a result of significantly lower late loss and loss index in cilostazol groups. The restenosis rate was significantly lower in cilostazol groups (12.5% in balloon-cilostazol group and 14.3% in stent-cilostazol group) than other groups (43.8% in balloon-aspirin group and 32.7% in stent-ticlopidine group). The rate of recurrent angina was significantly lower in cilostazol groups (4.3% in balloon-cilostazol group and 1.9% in stent-cilostazol group) than in other groups (17.5% in balloon-aspirin group and 14.0% in stent-ticlopidine groups). CONCLUSIONS: Both optimal balloon angioplasty with cilostazol and coronary artery stenting with cilostazol have a potential to reduce restenosis compared with optimal balloon angioplasty with aspirin or conventional coronary artery stenting with ticlopidine plus aspirin.     

冠脉支架植入术后支架内再狭窄的危险因素研究

目的对冠脉支架植入术后的支架内再狭窄危险因素进行研究。方法在2011年7月-2013年7月期间,我院收治冠脉支架植入术患者120例,对该120例患者术后支架内的再狭窄危险因素进行研究,并采取Logistic多因素分析再狭窄的危险因素。结果通过术后患者危险因素研究可知,与患者的胆固醇、术前狭窄、是否吸烟、有糖尿病及高血压等因素有关,与支架有无药物涂层也有关,表现为负相关,危险度是0.01。结论对糖尿病及高血压患者来说,实施支架植入术之后,出现再狭窄症状的几率增加。同时,冠脉支架患者对危险因素应采取预防措施,如戒烟,避免再狭窄情况出现,提高患者的生存质量。     

Systemic rapamycin without loading dose for restenosis prevention after coronary bare metal stent implantation

Objectives : The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation. Background : Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. Methods : This was prospective, open‐label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months. Results : Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in‐segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no‐therapy group, P < 0.001) and the in‐stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no‐therapy group, P < 0.001. The in‐segment late loss was also significantly reduced with oral therapy (0.29 ± 0.39 vs. 0.86 ± 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039). Conclusions : This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis. © 2009 Wiley‐Liss, Inc.     

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58+/-0.52 mm vs. 1.09+/-0.65 mm, P<.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs. 33%, P = .044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.     

曲美他嗪在预防冠状动脉支架置入后再狭窄的作用及其机制探讨

目的:探讨曲美他嗪维持治疗在预防冠状动脉支架置入后再狭窄(ISR)的效果。方法:随机选取2012年6月至2015年6月,入住我院且需要行经皮冠状动脉介入治疗的患者。经皮冠状动脉介入治疗和支架置入后,一部分患者给予1个月的曲美他嗪维持治疗,另一部分患者不给予曲美他嗪治疗。支架置入后12个月,冠状动脉造影检测血管的再狭窄情况。结果:此次研究共有507例患者参与,治疗组249例,对照组258例。在治疗后12个月的观察期中,对照组有29例患者出现了心脑主要不良事件,而治疗组有15例患者出现心脑主要不良事件。冠状动脉造影的结果显示共有37例患者出现了ISR,约占患者总数的7.3%,其中对照组为26例(10.1%),治疗组为11例(4.4%)。研究发现年龄、吸烟、糖尿病、支架的长度和支架的直径均与ISR的发生紧密相关(P<0.05)。曲美他嗪治疗具有更低的ISR风险,是独立的保护因素(P<0.05)。结论:曲美他嗪维持治疗能有效的预防冠状动脉ISR的发生,我们的研究为临床用药提供了理论指导。     

Effects of cilostazol on late lumen loss after Palmaz-Schatz stent implantation

Cilostazol inhibits intimal hyperplasia after stent implantation into canine iliac arteries. To determine the antiproliferative effect of this agent, cilostazol or aspirin was randomly given for 6 mo to 36 patients treated with Palmaz-Schatz stent implantation. Initial success was obtained in 34 patients. Repeat angiography was performed in 33 patients, and the complete angiographic data were obtained in 22 lesions of the cilostazol group and in 21 lesions of the aspirin group. The reference diameter and minimal luminal diameter were similar in both groups before and immediately after stent implantation. At follow-up, minimal luminal diameters were significantly greater in the cilostazol group than in the aspirin group (P < 0.001). Late loss and loss index were significantly smaller in the cilostazol group than in the aspirin group (P < 0.001). These results suggest that cilostazol reduces angiographic late lumen loss and thereby may reduce the incidence of restenosis after Palmaz-Schatz stent implantation. Cathet. Cardiovasc. Diagn. 44:387–391, 1998. © 1998 Wiley-Liss, Inc.     

Usefulness of cilostazol versus ticlopidine in coronary artery stenting

A combination of ticlopidine and aspirin has been accepted as the standard antithrombotic regimen after coronary stenting. However, ticlopidine poses serious side effects such as neutropenia or thrombocytopenia. Cilostazol, a cyclic adenosine monophosphate phosphodiesterase inhibitor, is a novel antiplatelet agent with vasodilatory properties. We compared the efficacy and safety of cilostazol plus aspirin (C+A) with ticlopidine plus aspirin (T+A) in elective coronary stenting. Three hundred patients were randomly assigned to receive C+A or T+A 2 days before stenting. The primary end point was a composite of angiographic stent thrombosis, or major cardiac events (death, myocardial infarction, bypass surgery, repeat intervention) at 30 days. The secondary end points were bleeding vascular complications, neutropenia, thrombocytopenia, or side effects requiring discontinuation of the drugs at 30 days. The primary end point was reached in 1.4% in the C+A group and 2.0% in the T+A group (p = 1.0). The rate of bleeding vascular complications was 1.4% in the C+A group and 2.0% in the T+A group (p = 1.0). The rate of drug-related side effects was not statistically different between the 2 groups but slightly higher in the T+A group than in the C+A group (2.7% vs 0.7%, p = 0.37). However, neutropenia was seen in 2 patients only in the T+A group. As a poststenting antithrombotic, C+A is as effective as T+A in preventing major cardiac events including stent thrombosis, and safer in that it does not cause neutropenia despite the fact that there is no statistical difference in the incidence of adverse effects and complications.