One-year clinical outcomes of Chinese sirolimus-eluting stent in the treatment of unselected patients with coronary artery disease

Abstract

The application of drug-eluting stent (DES), either sirolimus-eluting stent (Cypher, Cordis, USA) or paclitaxel-eluting stent (Taxus, Boston Scientific, USA), in treatment of patients with coronary artery disease (CAD) has achieved great success.1-4 The high cost of imported DES (either Cypher or Taxus) gave the birth to a China-made, polymer-based, sirolimus-eluting stent (Firebird, Microport Company, China). In March 2003, China Food and Drug Administration approved the clinical use of Firebird stent. However, the safety and efficacy of Firebird stent in comparison with Cypher and Taxus stents are still underestimated. METHODS Patients From May 1, 2003 to May 30, 2004, 673 consecutive patients with de novo coronary lesions were randomly divided into Firebird group (n=224), Cypher group (n=246) and Taxus group (n=203). Major exclusive criteria included: ①without informed consent; ② multi-vessel disease with favorable coronary artery bypass graft (CABG); ③ mild to moderate coronary stenosis (<70% diameter narrowing by online QCA); ④ vessel size > 3.5 mm or < 2.5 mm; ⑤ left ventricular ejection fraction (LVEF) < 0.30; and &2465; hemorrhagic diathesis or contraindications or allergy to the anti-platelet medications. Percutaneous coronary intervention Patients were pretreated with oral aspirin 100 mg/d and ticlopidine (250 mg, twice daily) or clopidogrel 75 mg/d at least 2 days before the procedure. For certain patients, a loading dose of clopidogrel 300 mg - 600 mg was applied at least 2 hours before emergency percutaneous coronary intervention (PCI). Coronary interventional procedure was performed according to the standard method.5 Procedural success was defined as residual stenosis ≤ 20% without in-hospital major clinical complications [including death, myocardial infarction (MI), emergency CABG].6 After procedures, patients treated with Firebird or Cypher stents received ticlopidine (500 mg/d for 4 weeks then 250 mg/d for at least 9 months) or clopidogrel (75 mg/d for at least 9 months). For those with Taxus stents, ticlopidine or clopidogrel was continued for at least 12 months. Aspirin 100 mg/d was prescribed indefinitely. End point definition and follow-up Follow-up information was obtained by telephone or outpatient interview. The primary composite end point was the occurrence of major adverse cardiac events (MACE) at 30 days and one year in all patients including death, nonfatal MI and target vessel revascularization (TVR). Statistical analysis Continuous variables were expressed as mean ± standard deviation (SD), and the comparison between groups was made using the unpaired Student's t test. The chi-square test was used to compare categoric variables. SPSS 10.0 was used for statistical analysis. A P value less than 0.05 was considered statistically significant. RESULTS Baseline and procedural characteristics The baseline clinical and angiographical characteristics among the three groups were similar. In Firebird group the number of stents implanted per patient was greater and mean total stents length was longer than those in the Cypher group or Taxus group. Procedural success rate was high for each group. The market price of Firebird, Cypher and Taxus stent were around ¥18 000, ¥30 000 and ¥21 000, respectively, the total cost for hospitalization in Firebird group was significantly lower as compared to that in the Cypher group. (Table 1)Table 1: Baseline and procedural characteristicsFollow-up outcomes At 30 days, one patient in the Taxus group had re-MI at 3 weeks after initial PCI, and was detected intra-stent thrombotic occlusion (TIMI 0) by angiography, which was treated by balloon angioplasty. At one year, death occurred in 1.9%, 2.3% and 2.7% of patients in the Firebird, Cypher, and Taxus groups respectively. MACE free survival was similar among the three groups. (Table 2)Table 2: Follow-up outcomes of the patients in different stent groups [n (%)]DISCUSSION Several clinical trials have demonstrated that DES could greatly reduce the MACE rate after PCI, even in the complex lesion subsets.4,7,8 The major advantage of DES is to reduce the late lumen loss at follow-up and the repeated revascularization. A recently published meta-analysis demonstrates tha the use of sirolimus- and paclitaxel-eluting stents significantly reduce the MACE (OR 0.35, 95% CI 0.24-0.50), restenosis rate (OR 0.27, 95% CI 0.15-0.47) and late loss of lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68).9 The introduction of imported DES (Cypher and Taxus) into China has significantly improved the clinical outcomes of PCI and its high cost promotes the speed of developing domestic and cheaper DES. For each Firebird stent, 9 μg sirolimus/mm is loaded in the matrix, which is top-coated with another polymer serving as a diffusion barrier. The present study shows that there is no significant difference among the Firebird, Cypher and Taxus groups with respect to the incidences of death, MI, TVR, or the composition at 30-day and one-year follow-up. Percent nine of MACE rate in the Firebird group at one-year is similar to that in the Cypher group, also comparable to the results from RESEARCH study (9.7%).2 When compared to the Taxus stents, the MACE in Firebird group at one-year follow-up is slightly lower, but does not reach statistically significant level. Similar results is concluded from T-RESEARCH registry analysis in which the raw cumulative incidence of MACE is 10.5% in patients treated with sirolimus-eluting stents and 13.9% in those with paclitaxel-eluting stents at one-year follow-up.10 Stent thrombosis is a major concern for DES. Delayed endothelialization after implantation of DES may extend the risk of thrombosis. Previous studies demonstrate the lower incidence of stent thrombosis after sirolimus-eluting stenting (0.4% at 1 year) or paclitaxel-eluting stents (0.9% at 9 months).7,11 A lastly published meta-analysis study by Merona et al12 reports the overall rates of stent thrombosis do not differ significantly between patients receiving sirolimus- and paclitaxel-eluting stents (0.57% vs 0.58%). In our study, only 2 patients (1.0%) with Firebird stents are diagnosed as stent thrombosis by angiography at 2 months and 5 months, respectively, and no significant difference is found as compared to the Cypher group (0.9%) and Taxus group (1.6%). Furthermore, none dies from stent thrombosis during follow-up in all groups. The current result is more comparable to that from a "real world" study conducted by Iakovou et al,13 in which 1.3% of the patients receiving Cypher stents and 1.7% with Taxus stents have stent thrombosis at 9 months' follow-up. Independent predictors of stent thrombosis include premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes and a lower ejection fraction. The significantly reduced hospitalization cost in Firebird group is obvious in our study, which is due mostly to the lower cost of the Firebird stents than the imported Cypher or Taxus stents, especially for patients with multi-vessel disease. In conclusion, the unrestricted use of the China-made Firebird sirolimus-eluting stents for PCI is safe and associated with a non-significant difference in clinical outcomes at one-year compared to the imported Cypher or Taxus stents. The less expense of Firebird stent makes it more attractive for treating the patients with multi-vessel disease in China.