Comparison of Three-Year Clinical Outcome of the Multi-Link Stent with the Palmaz-Schatz Stent in Japanese Patients with Coronar

Prospective randomized trials of coronary stenting with the Palmaz-Schatz (PS) stent (Cordis Corporation, Miami, Florida) in stable angina1,2 or in acute myocardial infarction3,4 have shown a reduced incidence of cardiac events. However, the PS stent has several disadvantages, including rigidity, difficult passage through tortuous anatomy or angulated lesions, and poor scaffolding in the articulation site. Therefore, several new (second generation) stents have been developed and have better deliverability than the PS stent. The ACS Multi-Link (ML) stent (Guidant Corporation, Santa Clara, California) is one of the new stents and the results of the trials with the ML stent were similar or slightly superior to the PS stent.5–7 Nevertheless, these trials documented only relatively short-term (Patient population. The study population consisted of 52 patients who underwent successful coronary angioplasty and ML stent implantation (ML group; case) and 52 patients who underwent successful coronary angioplasty and PS stent implantation (PS group; control) from October 1997 to September 1999 in our hospital. Both groups were closely matched in terms of age, gender, indications for angioplasty and angiographic findings (American College of Cardiology/American Heart Association [ACC/AHA]) lesion type, site of stenting]. Both patient groups were prospectively enrolled in pairs. All patients were enrolled after written informed consent, and the study protocol was based on the regulations of the ethics committee of our hospital. The clinical characteristics of all subjects are summarized in Table 1. The characteristics include age, gender, coronary risk factors (hypertension, hypercholesterolemia, diabetes mellitus, smoking), indications for angioplasty, site of angioplasty and drug treatment given after coronary stenting (nitrates, nicorandil, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, antiplatelets and warfarin). Coronary stenting and quantitative coronary angiography. The angiographic characteristics of all subjects are summarized in Table 2. Conventional balloon angioplasty was the only procedure carried out in all patients before stent implantation. Balloon or stent size and pressure were at operator discretion. Multiple stents were deployed if necessary to cover the full extent of the target lesion or the dissection if it occurred. Procedural success was defined as the successful deployment of the stent and residual stenosis less than 30% on quantitative coronary angiography. After deployment of the stent, adjunctive postdilation was performed to achieve a residual stenosis less than 30%. All patients received intravenous heparin (150 IU/kg) during the procedure and all received antiplatelet (aspirin 81 mg/day, and ticlopidine 200 mg/day or cilostazol 200 mg/day) for at least 6 months after the procedure. Quantitative coronary angiography was performed using a Philips DCI-ACA imaging system. The contrast-filled guiding catheter was used as a reference. Intracoronary isosorbide dinitrate (3.0 mg) was administered before all angiographic assessments. The diameters of the normal segments proximal and distal to the treated area were averaged to determine the reference diameter. The minimum lumen diameter and the percentage of diameter stenosis after coronary stenting were calculated by single-plane, worst-view angulation. Lesions of coronary stenting were characterized according to the modified ACC/AHA characteristics.8,9 Clinical and angiographic follow-up. All patients had follow-up coronary angiography. Angiographic restenosis was defined as > 50% diameter stenosis at follow-up coronary angiography. Target lesion revascularization was indicated by the presence of clinical or functional ischemia and > 75% diameter stenosis or a restenosed lesion > 90% in the absence of documented ischemia. Clinical follow-up data were obtained by either hospital records or telephone contact with the patient or the referring physicians. Cardiac events were defined as cardiac death, myocardial infarction, coronary artery bypass graft surgery, repeat coronary angioplasty of the target lesion and nonstented lesions (new lesion). Bypass graft surgery was defined as any surgical revascularization, even if the stented segment was patent. In-hospital events were included in the analysis of follow-up events. Statistical analysis. All data are expressed as means ± standard deviation. The difference in mean values between the 2 groups was compared using an unpaired t-test. The incidences in the 2 groups were compared using the Chi-square test. A cardiac event-free curve was created by the Kaplan-Meier method to determine the time-dependent cumulative event-free rate and compared using log rank tests. A p-value less than 0.05 was considered significant. Results Table 1 shows the clinical characteristics of the 2 groups. There were no significant differences between the groups in terms of age, gender, coronary risk factors or drugs taken after coronary stenting. Two patients in the ML group and 4 patients in the PS group took warfarin for 6 months because of thrombus formation in the left ventricle. One patient in the PS group took warfarin during the follow-up period to prevent cerebral infarction, since this patient had atrial fibrillation and had previously developed cerebral infarction. There was no significant difference between the 2 groups in the number of subjects who had previous myocardial infarction (11 in the ML group, 7 in the PS group) and previous angioplasty (8 in the ML group, 7 in the PS group). Table 2 shows the angiographic characteristics of the 2 groups. There was no significant difference in the number of subjects with multivessel disease (10 in the ML group, 13 in the PS group) or multiple stenting (6 in the ML group, 11 in the PS group). The distribution of the stented arteries (left anterior descending, n = 31; right coronary artery, n = 17; left circumflex, n = 4) and indications for angioplasty (stable angina, n = 21; unstable angina, n = 11; acute myocardial infarction, n = 20) were the same in each group. ACC/AHA lesion type was also matched in both groups. However, in patients with type C lesions, the ML group had a significantly higher incidence of tortuosity of the proximal segment than the PS group. Postprocedural quantitative coronary angiographic findings (reference diameter, minimal luminal diameter, percent diameter stenosis) between the 2 groups were the same. Table 3 shows cardiac events of the 2 groups during the follow-up period. There were no significant differences between the groups in terms of target lesion revascularization, angiographic restenosis and any cardiac event. During the follow-up period, cardiac events were documented in 11 of the 52 ML patients (21%) and in 14 of the 52 PS patients (27%) (p = NS). The rates of survival free of cardiac events were 79% in the ML group and 73% in the PS group at 3 years (p = NS) (Figure 1). Figure 2 shows the angiographic restenosis rates in both groups. Angiographic restenosis rates of ACC/AHA lesion type A or B1 were 8.3% in both groups, and of ACC/AHA lesion type B2 or C were 39.3% in the ML group and 35.7% in the PS group (p = NS). In addition, angiographic restenosis rates of ACC/AHA lesion type A or B1 were significantly lower than those of lesion type B2 or C in both groups. Discussion The results of the present study suggest that 6-month angiographic and 3-year clinical outcomes in patients with coronary artery disease treated by coronary stenting with the ML stent were comparable to those with the PS stent. Clinical outcome after coronary PS stent implantation. The multicenter Stent Restenosis Study (STRESS)1 and BENESTENT2 trials have demonstrated a decrease in both angiographic restenosis and the need for repeat revascularization in the first year for vessels treated by PS stent implantation rather than conventional balloon angioplasty. In terms of long-term outcome, Kimura et al.10 reported the results of a 3-year follow-up study in 143 patients, with a 74.6% rate of survival free of myocardial infarction, bypass surgery and repeat angioplasty for stented lesions. Laham et al.11 published data on the long-term (4–6 year) outcome of PS stenting in native coronary arteries and saphenous vein grafts. The survival rate was 86.7% and the target lesion revascularization rate was 19.8% at 5 years. Moreover, the long-term follow-up results of the BENESTENT-I trial12 showed that the original difference of 10% in target lesion revascularization in favor of the stent group compared to the balloon angioplasty group has remained unchanged at 5 years. Those results show stability of the lesions treated by PS stents, with only a slight increase in target lesion revascularization after 1 year. Clinical outcome after coronary ML stent implantation compared to the PS stent. The WEST trial,5 which assessed the efficacy of the ML stent, showed a 12% rate of in-stent restenosis at 6-month follow-up angiography and 85% of the patients were free of angina pectoris at 12 months. The MIAMI trial6 showed that a primary endpoint (death, reinfarction, target vessel revascularization) occurred in 15% and angiographic restenosis occurred in 22% of patients with acute myocardial infarction within 6 months of ML stent implantation. The results of the ASCENT trial7 using the ML stent showed that target vessel failure (death, myocardial infarction, repeat target vessel revascularization) occurred in 15.1% of the patients within 9 months of ML stent implantation. The results within 12 months are similar to or slightly better than those of trials using the PS stent. However, the long-term clinical outcome of ML stenting is less well described. We previously reported relative long-term (2-year) outcomes after ML stent implantation with a 14.6% rate of target lesion revascularization.13 In the present study, we compared 3-year clinical outcomes of the ML stent with the PS stent. The rate of target lesion revascularization was same in both groups (17% in the ML group, 19% in the PS group) and the rate of survival free of cardiac events at 3 years was also similar in both groups (21% in the ML group, 27% in the PS group). These findings suggest that not only short-term outcomes but also long-term (3-year) clinical outcomes in patients with coronary artery disease successfully treated with the ML stent are similar to those with the PS stent and favorable. ACC/AHA lesion characteristics of the stented lesion and clinical outcomes. The ML stent is flexible due to a low metal surface and thin struts, which can also be of value for the access of tortuous vessels. Previous studies demonstrated that the ML stent had better deliverability than the PS stent, and achieved high procedure success rates.5–7 Indeed, in the present study, type C lesions in the ML group included excessive tortuosity of proximal segments (> 90°) in 5 patients and location in an extremely angulated segments in 3 patients. This result shows that the ML stent might be a very useful stent for tortuous or angulated lesions that are difficult to cross with the PS stent. We previously reported that ACC/AHA lesion type was identified as an independent predictor of cardiac events after coronary stent implantation.14 In the present study, the angiographic restenosis rate of lesion type A or B1 was also lower than lesion type B2 or C in both the ML and PS groups. In addition, clinical and angiographic results of both groups were also similar in the ACC/AHA type C lesions. Thus, a close match in terms of ACC/AHA lesion type in both groups was important to compare clinical and angiographic results of both groups. Study limitations. The ML stent group subjects and the PS stent group subjects were enrolled prospectively, but the study was not designed as a prospective randomized trial. The results from the 104 patients strongly suggest the need for a larger patient population; the number of patients in each group (52) might be too small to detect any potential differences in outcome between the two studied groups and the follow-up period of 3 years was still short. Further studies using a larger patient population and with longer follow-up periods are therefore needed to compare the exact long-term outcome after ML and PS stent implantation in patients with coronary artery disease. Acknowledgments. We are deeply grateful to the staff (Tatsuo Kawaguchi, Tadao Ishido, Syouji Sasaya, Taku Igarashi, Atsushi Takahashi) of the catheterization laboratory in our hospital for their excellent technical assistance. We express special thanks to Hitomi Kimura and Hiromi Akutsu for preparing the manuscript.

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