Randomized comparison of cilostazol vs clopidogrel after drug-eluting stenting in diabetic patients--clilostazol for diabetic patients in drug-eluting stent (CIDES) trial.

BACKGROUND: Previous studies have shown that cilostazol may not only prevent stent thrombosis, but may also have positive effect in the prevention of restenosis. However, the effect of cilostazol on restenosis after successful deployment of drug-eluting stent (DES) in patients with diabetes mellitus has not been evaluated. METHODS AND RESULTS: A total of 280 patients at 8 clinical sites were randomized. The patients (61.7+/-9.9 years old, 163 males) who underwent successful stenting were randomized to aspirin and cilostazol (group I, n=141, 61.2+/-9.6 years old) vs aspirin and clopidogrel (group II, n=139, 62.0+/-10.0 years old) after 1 month of aspirin, cilostazol, and clopidogrel combination treatment. There were no significant differences in baseline characteristics of the groups. The type of DES implanted did not differ between the groups. There were no differences in angiographic and procedural characteristics of the groups. Major adverse cardiac events, including acute and subacute stent thrombosis within 1 month, did not occur in either group. Cases of angiographic late stent thrombosis were 1 (0.9%) in group I and 1 (0.8%) in group II. Follow-up coronary angiography was performed in 237 patients (84.6%). Mean follow-up duration was 7.1 months. The rate of angiographic restenosis (stent plus 5-mm borders) was 9 (8.0%) in group I and 20 (16.1%) in group II, p=0.041). The minimal luminal diameter at follow-up period in group I was 2.55+/-0.63 mm compared with 2.41+/-0.83 mm in group II (p=NS). CONCLUSIONS: Combination therapy with aspirin and cilostazol for the prevention of stent restenosis is comparable or superior to that of aspirin and clopidogrel in diabetic patients who undergo DES implantation.     

Lack of efficacy and cost-effectiveness of drug-eluting stents: reply

We agree with Lyratzopoulos that drug-eluting stents (DES) lackany survival benefit compared with bare-metal stents (BMSs)for patients with chronic     

Prevalence and clinical impact of stent fractures after femoropopliteal stenting

OBJECTIVES: The aim of this study was to investigate the occurrence and the clinical impact of stent fractures after femoropopliteal stenting. BACKGROUND: The development of femoral stent fractures has recently been described; however, there are no data about the frequency and the clinical relevance. METHODS: A systematic X-ray screening for stent fractures was performed in 93 patients. In total, 121 legs treated by implantation of self-expanding nitinol stents were investigated after a mean follow-up time of 10.7 months. The mean length of the stented segment was 15.7 cm. RESULTS: Overall, stent fractures were detected in 45 of 121 treated legs (37.2%). In a stent-based analysis, 64 of 261 stents (24.5%) showed fractures, which were classified as minor (single strut fracture) in 31 cases (48.4%), moderate (fracture of >1 strut) in 17 cases (26.6%), and severe (complete separation of stent segments) in 16 cases (25.0%). Fracture rates were 13.2% for stented length < or =8 cm, 42.4% for stented length >8 to 16 cm, and 52.0% for stented length >16 cm. In 21 cases (32.8%) there was a restenosis of >50% diameter reduction at the site of stent fracture. In 22 cases (34.4%) with stent fracture there was a total stent reocclusion. According to Kaplan-Meier estimates, the primary patency rate at 12 months was significantly lower for patients with stent fractures (41.1% vs. 84.3%, p < 0.0001). CONCLUSIONS: There is a considerable risk of stent fractures after long segment femoral artery stenting, which is associated with a higher in-stent restenosis and reocclusion rate.     

Comparison of cilostazol and clopidogrel after successful coronary stenting

This study compared the safety and efficacy of cilostazol and clopidogrel after coronary stenting. Patients (n = 689) who underwent successful stenting were randomly assigned to receive cilostazol (group 1, n = 344, 612 lesions) or clopidogrel (group 2, n = 345, 628 lesions). The incidence of subacute stent thrombosis or major adverse cardiac events, including death, myocardial infarction, and target lesion revascularization within 30 days (2.6% in group 1 vs 2.0% in group 2, p = 0.61) and side effects that required cessation of study drug (0.6% each) did not differ statistically between groups. These results indicate that cilostazol is as safe and effective as clopidogrel in preventing thrombotic complications after stenting.     

Lack of efficacy of clopidogrel pre-treatment in the prevention of myocardial damage after elective stent implantation

OBJECTIVES: The object of this study was to determine the effect of pre-treatment with clopidogrel in patients undergoing elective stent implantation. BACKGROUND: The treatment of patients with adenosine diphosphate receptor blockers after percutaneous coronary intervention (PCI) with stent implantation has been shown to decrease the incidence of subacute stent thrombosis. Furthermore, non-randomized studies on pre-treatment with clopidogrel among patients undergoing stent implantation have suggested a reduction in myocardial damage and clinical events. The effect of pre-treatment with clopidogrel has been studied in only a few randomized trials. METHODS: In a randomized trial, three days of pre-treatment with clopidogrel was compared with standard post-procedural treatment in 203 patients undergoing elective stent implantation. The primary end point was a rise in troponin I or creatine kinase-MB fraction (CK-MB) serum levels at 6 to 8 and 16 to 24 h after PCI. Secondary end points were death, stroke, myocardial infarction, coronary bypass grafting, repeated PCI, and subacute stent thrombosis at one and six months after PCI. RESULTS: No difference was found between non-pre-treated and pre-treated patients in the post-procedural elevation of troponin I (42 [43.3%] vs. 48 [51.1%], respectively, p = 0.31) or CK-MB (6 [6.3%] vs. 7 [7.4%], respectively, p = 0.78). Adjustment for possible confounding factors did not change these findings. Patient follow-up at one and six months showed no significant difference between the treatment groups in death, stroke, myocardial infarction, coronary artery bypass grafting, repeated PCI, or subacute stent thrombosis. CONCLUSIONS: In this randomized study, no beneficial effect of pre-treatment with clopidogrel on post-procedural elevation of troponin I and CK-MB or on clinical events after one and sixth months could be demonstrated. The study suggests that among patients with stable coronary syndromes in whom coronary stent implantation is planned, pre-treatment may not be beneficial in reducing early myocardial damage.     

Comparison of efficacy and safety of treatment with drugs of clopidogrel in patients after coronary artery stenting

Proof of clinical equivalence of generic and original dugs - the way to lessen cost of therapy of patients while providing comparable clinical effects. We present in this paper results of 1 year follow-up of 115 patients receiving Egithromb or Plavics after coronary artery stenting. Comparable clinical efficacy and safety of Egithromb and Plavics has been established.     

Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.

OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivit?ts Trial). The primary focus of this observation was cardiac death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.     

An updated meta-analysis of calcium-channel blockers in the prevention of restenosis after coronary angioplasty

Background In 1994, a meta-analysis of 5 small randomized trials reported a 30% reduction in the odds of angiographic restenosis when calcium-channel blockers (CCB) were given after percutaneous coronary intervention. Recently, the results of 2 large similar trials (Nisoldipine In Coronary Artery Disease in Leuven [NICOLE], and Coronary AngioPlasty Amlodipine in REstenosis Study [CAPARES]) were published. An extended meta-analysis including the results of the latter trials was performed. Methods A total of 2380 patients were analyzed. Statistical analysis included calculation of odds ratios for each trial, common odds ratio, and homogeneity for treatment effects across trials. Results The incidence of angiographic restenosis was 36% in the CCB-treated group and 42% in the placebo group. The odds ratio of restenosis with CCB therapy was 0.78 (95% CI 0.64-0.95) compared with control patients (P = .01). Treatment effects were homogeneous across the trials. For the combined end point of death, coronary artery bypass grafting, repeat percutaneous transluminal coronary angioplasty, and myocardial infarction, 126 of 626 events occurred in the CCB group and 191 of 655 in the placebo group (odds ratio 0.61 [95% CI 0.47-0.80], P < .001). Conclusions This extended meta-analysis confirmed a reduction in the odds of restenosis and clinical events when CCBs were added to standard therapy after percutaneous coronary intervention. (Am Heart J 2003; 145:404-8.)     

Basic cellular mechanisms of action of the calcium-channel blockers

Calcium-channel blockers inhibit the entry of calcium ion (Ca++) into excitable cells, including those of coronary and peripheral arterial smooth muscle and the heart. The ability of these drugs to block Ca++ entry into cells inhibits the essential role of this cation as an intracellular messenger. The effects of calcium-channel blockers on the heart include a negative inotropic effect on the working myocardial cells of the atria and ventricles. Because the up-stroke of the action potential in these regions of the heart, and in the rapidly conducting cells of the His-Purkinje system, is due to a fast, sodium-dependent ionic current, calcium-channel blockers do not inhibit conduction in these cells. In the sinoatrial and atrioventricular (AV) nodes, on the other hand, depolarization is due primarily to a Ca++-dependent slow inward current; as a result, the calcium-channel blockers inhibit the sinus pacemaker and AV conduction. Because our knowledge of the molecular structure of the calcium channels in the heart and smooth muscle is rudimentary, little is known of the molecular mechanisms by which calcium-channel blockers inhibit Ca++ entry across the sarcolemmal membranes in these cells. It is apparent, however, that the actions of different members of this class of drugs on the sarcolemma are not the same. Indirect evidence indicates that some members of this class of drugs may interact with hydrophobic regions of the proteins that make up, or regulate, the calcium channels in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)