A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents

OBJECTIVES: The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up. BACKGROUND: Randomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days. METHODS: After successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months. RESULTS: Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002). CONCLUSIONS: After the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies.     

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.     

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.     

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。     

Combination therapy with aspirin plus clopidogrel versus aspirin plus ticlopidine for prevention of subacute thrombosis after successful native coronary stenting

We compared the combination of aspirin plus clopidrogrel (A+C) with aspirin and ticlopidine (A+T) for prevention of subacute stent thrombosis in 827 patients. At 30-day follow-up, there were trends toward increased subacute thrombosis with A+C compared with A+T (1.3% vs 0.2%, p = 0.10). These results suggest that A+C may have marginally higher subacute stent thrombosis than A+T.     

Efficacy and safety of aspirin,clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS₂ score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02–59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan–Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.     

A randomized comparison of direct stenting versus stenting with predilatation in native coronary artery disease: results from the multicentric Crosscut study

Stenting without predilatation has become possible due to the availability of a new generation of flexible, low-profile, securely crimped, balloon-expandable stents. This study compared the feasibility, efficacy and cost-effectiveness of direct stenting (DS) to the standard predilatation technique (PS) using the premounted Crossflex LC stent (Cordis Corporation, Miami Lakes, Florida). The study is a randomized prospective multicenter evaluation including 271 patients (140 patients in the DS group and 131 patients in the PS group) with 1 or 2 de novo or restenotic lesions located in native coronary arteries. Procedural success was 98.9% and 98.7% in the DS and PS groups, respectively (p = NS); crossover to PS was required in 22/166 lesions (13.2%) enrolled in the DS group because of inability to cross the target lesion without predilatation. Nonsignificant reductions in procedural time (-10.5%), fluoroscopy time (-4.7%) and amount of contrast (-3.8%) were observed in the DS group in comparison to the PS group. The number of balloons used (-76.6%) and the global cost of the procedure (-18.8%) were significantly lower in the DS group (p < 0.01 for both comparisons). After 6 months, no differences were observed in the restenosis rate between the two groups (22.0% for DS group versus 18.1% for PS group; p = NS) and in the incidence of major adverse clinical events (5.0% for DS group versus 3.0% for PS group; p = NS). Direct stenting is safe and feasible for the treatment of lesions in native coronary arteries and obtains a significant reduction in procedural cost, mainly due to the lower number of balloons used. Clinical and angiographic results at 6 months are comparable to those obtained after a conventional predilatation-stenting strategy.     

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.     

Efficacy and safety of individually tailored antiplatelet therapy in patients with acute coronary syndrome after coronary stenting: a single center, randomized, feasibility study

Background Low responsiveness to clopidogrel (LRC) is associated with increased risk of ischemic events. This study was aimed to explore the feasibility of tailored antiplatelet therapy according to the responsiveness to clopidogrel. Methods A total of 305 clopidogrel naive patients with acute coronary syndromes (ACS) undergoing coronary stenting were randomly assigned to receive standard (n = 151) or tailored (n = 154) antiplatelet therapy. The ADP-induced platelet aggregation tests by light transmission aggregometry were performed to identify LRC patients assigned to the tailored group. The standard antiplatelet regimen was dual antiplatelet therapy with aspirin and clopidogrel. The tailored antiplatelet therapy was standard regimen for non-LRC patients and an additional 6-month cilostazol treatment for LRC patients. The primary efficacy outcome was the composite of cardiovascular death, myocardial infarction or stroke at one year. Results LCR was present in 26.6% (41/154) of patients in the tailored group. The percentage platelet aggregation for LCR patients was significantly decreased at three days after adjunctive cilostazol treatment (77.5% ± 12.1% vs. 64.5% ± 12.1%, P < 0.001). At one year follow-up, a non-significant 37% relative risk reduction of primary events were observed in the tailored group as compared to the standard group (5.8% vs. 9.3%, P = 0.257). There were no differences in the rates of stent thrombosis and hemorrhagic events between the two groups. Conclusions Tailored antiplatelet therapy for ACS patients after coronary stenting according to responsiveness to clopidogrel is feasible. However, its efficacy and safety need further confirmation by clinical trials with larger sample sizes.     

Comparison of clopidogrel versus ticlopidine for prevention of minor myocardial injury after elective coronary stenting

We searched a randomized, double-blinded, prospective study that compared the effectiveness of clopidogrel versus ticlopidine for prevention of minor myocardial injury (MMI) and major clinical events (MCEs) after elective coronary stenting. A total of 158 consecutive patients (98 male, 60 female patients with a mean age of 59.3+/-5.4 years) were divided into two arms based on treatment with thienopyridines: group I, clopidogrel 1 x 300 mg as a loading dose, and 1 x 75 mg per day thereafter, group II, ticlopidine 2 x 250 mg daily. Both thienopyridines were started on the same day as stent placement. Cardiac troponin T (cTnT) was measured immediately before and 12 h after the procedures. All patients were followed-up during the hospital stay (6+/-2 days) with respect to MMI and MCEs. The increase frequency and the amount of cTnT level in group I was found significantly lower compared with group II (5 vs.15; P<0.01; 0.38+/-0.11 vs. 0.44+/-0.12 ng/ml; P<0.001, respectively). Patients with elevated cTnT levels more likely to have C type lesion (P<0.004). Though there was a trend toward increased major clinical events rate in group II than those of group I, the statistical difference was not different (4 vs. 1.3%; P>0.05). The present study showed that the combination of clopidogrel and aspirin was more effective than the combination of ticlopidine and aspirin in decreasing the rate of MMI.     

无保护左主干病变的介入治疗及随访结果

目的 :探讨无保护左主干病变患者冠状动脉 (冠脉 )内支架术的近、远期疗效。方法 :共选择 8例均无冠脉搭桥术史的左主干病变患者行冠脉内支架术 ,其中左主干近中段病变 5例 ,远段分叉病变 3例 ,其中 2例的左室射血分数 <4 0 % ,总结分析其临床、左主干病变特点、手术成功率及随访结果。结果 :左主干支架术的成功率为 10 0 % ,无残余狭窄或残余狭窄率 <10 % ,无任何严重并发症如支架内血栓形成、急性心肌梗死、紧急外科冠脉搭桥术或死亡等。术后随访 5～ 15 (10± 3.5 )个月 ,无一例死亡。临床心绞痛复发 1例 ,重复冠脉造影证明为前降支的新生病变所致 ;2例左室功能不全患者的左室射血分数提高了 15 %以上 ;5例复查了冠脉造影 ,其中 4例的原支架内基本无再狭窄 ;1例有 30 %再狭窄 (为前述症状复发的患者 )。结论 :支架置入术治疗无保护左主干病变疗效显著 ,是值得考虑的治疗手段 ;正确的病例选择和娴熟的操作技巧是手术成功的关键     

Intracoronary stenting and angiographic results: Restenosis after direct stenting versus stenting with predilation in patients with symptomatic coronary artery disease (ISAR-DIRECT trial).

The objective of this randomized study was to assess whether direct stenting leads to less restenosis than does conventional stenting (CS) with predilation in clinical practice. We included 910 patients who were randomly assigned to undergo either direct stenting (DS; n = 456) or CS (n = 454). No significant difference was observed in the incidence of angiographic restenosis (primary endpoint): 23.6% for DS and 21.0% for CS (P = 0.41; relative risk = 1.1; 95% CI = 0.8-1.5). The incidence of target vessel revascularization was 17.3% among DS and 14.8% among CS patients (P = 0.29; relative risk = 1.2; 95% CI = 0.8-1.6). The combined incidence of death or myocardial infarction at one year was 9.0% in the DS group and 7.0% in the CS group (P = 0.28). In conclusion, direct stenting is not associated with any reduction of thrombotic and restenotic complications as compared to the conventional stenting.     

Direct coronary stenting versus stenting with balloon pre-dilation: immediate and follow-up results of a multicentre, prospective, randomized study. The DISCO trial. DIrect Stenting of COronary Arteries.

AIMS: To assess the safety of direct coronary stenting, its influence on costs, duration of the procedure, radiation exposure, clinical outcome and angiographic restenosis. METHODS AND RESULTS: We randomized 416 patients (446 lesions) to direct stent implant or stent implant following balloon pre-dilation. Patients >75 years old, heavily calcified lesions, bifurcations, total occlusions, left main lesions and very tortuous vessels were excluded. Direct stenting was successful in 217/224 lesions (96.8%). No single loss or embolization of the stent occurred. All stents in the group with pre-dilation were effectively deployed. The immediate post-procedure angiographic results were similar with both techniques. Fluoroscopy and procedural time were significantly lower in direct stenting (6.4+/-0.3 and 21+/-0.9 min) than in pre-dilated stenting (9.1+/-0.4 and 27.5+/-1.1 min) (P>0.001). Major adverse cardiac events during hospitalization were one in direct and four in pre-dilated stenting (P=0.05) but there were no significant differences at follow-ups at 1, 6 and 12 months between the two groups. Angiographic reevaluation at 6 months was performed in 94% of the cases. Restenosis rate was 16.5% in direct stenting and 14.3% in pre-dilated stenting (P=ns). CONCLUSIONS: Direct stenting is as safe as pre-dilated stenting in selected coronary lesions. Acute angiographic results are similar but procedural costs, duration of the procedure and radiation exposure are lower in direct stenting. Overall success rate, mid-term clinical outcome and restenosis are similar with both techniques.     

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.