Efficacy and safety of a double-coated paclitaxel-eluting coronary stent: the EUCATAX trial.

OBJECTIVES: The aim of this study was the comparison of a new double-coated paclitaxel-eluting coronary stent with bare-metal stent (BMS) in patients undergoing percutaneous coronary intervention. BACKGROUND: Stent coating with biodegradable polymers as a platform for elution of drugs has the potential for complete elution of drugs and for decreasing the risk of late complications. METHODS: Multicenter randomized trial comparing a paclitaxel-eluting stent (PES) coated with a biodegradable polymer and glycocalyx with the equivalent BMS. We randomly assigned 422 patients with de novo coronary lesions to PES (211 patients) or to BMS (211 patients). Primary end point was target vessel failure (TVF) defined as cardiac death, myocardial infarction, and target vessel revascularization. Clinical secondary end points were target vessel revascularization, target lesion revascularization, stent thrombosis (ST), and major adverse cardiovascular events (MACE). Angiographic secondary end points were late loss and binary restenosis. RESULTS: At 1 year of follow-up, TVF rate was 9.5% in the PES group and 17.1% in the BMS group (P=0.02), and MACE rate was 10% in PES and 19% in BMS arm (P=0.009). All other secondary end points were reached but ST. ST rate was low and similar in both study arms. CONCLUSIONS: The study shows that patients treated with PES with dual coating technology had significantly lower incidence of TVF and MACE than those treated with BMS design; however, longer follow-up should be necessary to assess true advantages of this technology compared with the previous one.

Pilot study of oral rapamycin to prevent restenosis in patients undergoing coronary stent therapy: Argentina Single-Center Study (ORAR Trial).

Rapamycin-coated stents are associated with low restenosis rates, but the ability of oral rapamycin to prevent restenosis is unknown. From December 2001 through February 2002, thirty-four patients with 49 lesions were treated with oral rapamycin for 1 month following percutaneous coronary intervention (PCI) with bare stents. Patients received a loading dose of 6 mg rapamycin followed by a daily dose of 2 mg. Rapamycin blood levels were measured in all patients during the third week of treatment. Cholesterol and triglycerides were evaluated before and 1 month after treatment. A 6-month follow-up angiogram was performed in all patients. Angiographic binary restenosis (> 50%), target lesion revascularization (TLR), late loss, treatment compliance and major adverse cardiac events were analyzed independent of rapamycin levels. Baseline characteristics included a history of diabetes in 35% of patients and the presence of in-stent restenosis in 24.5% of lesions (12/49). The rapamycin was well tolerated and only 1 patient discontinued the therapy due to mild side effects. Angiographic restenosis and TLR at 6 months was present in 26.5% of lesions (13/49). Restenosis in de novo lesions was 18.9% (7/37) compared to 50% of in-stent restenotic lesions (6/12; p = 0.08). Restenosis in de novo lesions in patients with rapamycin levels > 8 ng/ml was 0% (0/12), whereas it was 24% (6/25) when the rapamycin levels were < 8 ng/ml (p = 0.07). Late loss was significantly lower when rapamycin levels were > 8 ng/ml (0.3 mm versus 0.9 mm, respectively; p = 0.04). Thus, in this observational study, oral rapamycin administered for 1 month after PCI with bare stenting was safe and well tolerated. Higher therapeutic rapamycin blood levels were associated with a lower late loss and a trend toward a lower restenosis rate in de novo lesions.

Revascularization strategies of coronary multiple vessel disease in the Drug Eluting Stent Era: one year follow-up results of the ERACI III Trial.

OBJECTIVE: To compare the incidence of major adverse cardiac and cerebrovascular events (MACCE) in patients with multiple vessel coronary artery disease treated with drug eluted stents (DES), bare metal stents, percutaneous coronary interventions (PCI) or bypass surgery (CABG). METHODS: In the Argentine Randomized Study Coronary Angioplasty versus Coronary Bypass Surgery in Multiple Vessel Disease (ERACI) III trial, 225 patients with multivessel disease who received DES met clinical and angiographic inclusion criteria for the ERACI II trial. This cohort (ERACI III-DES) was compared to both ERACI II treatment arms (ERACII-PCI and ERACI II-CABG). The primary end point was freedom from MACCE at one year. RESULTS: Comparison of baseline demographic and angiographic data, revealed that ERACI III-DES patients were older, smoked more, had more diabetes, hyperlipidaemia, hypertension, type C lesions and received more stents. At one year freedom from MACCE was significantly greater in ERACI III-DES cohort (88%) than ERACI II CABG (80.5% p=0.038) and ERACI II PCI (78% p=0.006) patients. The ERACI III-DES cohort had similar freedom from death and acute myocardial infarction (AMI) to ERACI II PCI patients but greater than ERACI II-CABG arm. Freedom from repeat revascularization was similar between ERACI III-DES to ERACI II-CABG (95.1% p=ns) patients, but both were significantly better than those in the ERACI II-PCI arm ( 91.2% and 83%p=0.002 and 0.02 respectively). CONCLUSION: Patients with multiple vessel disease treated with DES in ERACI III had better one year outcomes than those treated with PCI or CABG in ERACI II.

Oral rapamycin after coronary bare-metal stent implantation to prevent restenosis: the Prospective, Randomized Oral Rapamycin in Argentina (ORAR II) Study.

OBJECTIVES: The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. BACKGROUND: Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. METHODS: Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. RESULTS: Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018). CONCLUSIONS: This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.