Long-Term Clinical Outcome of Sirolimus-Eluting Stent Implantation in Metabolic Syndrome and Diabetes
- Volume 22 - Issue 7 - July, 2010
- Posted on: 7/6/10
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ABSTRACT: Background. Patients with metabolic syndrome (MetS) are at increased risk of cardiovascular events. The long-term effectiveness of sirolimus-eluting stents (SES) in patients with MetS and in diabetic patients is not well defined. Methods. 563 consecutive patients with 629 de novo coronary lesions (< 50 mm lesion length, reference diameter < 3.5 mm) successfully treated with SES were enrolled in the study and followed for 41 ± 17 months. Bifurcation and left main lesions were excluded. Patients were categorized into three groups: 1) no MetS and no diabetes; 2) MetS and no diabetes; and 3) diabetes. MetS was defined as the presence of ≥ 3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, elevated fasting glucose. Results. 284 patients (51%) with 318 lesions had neither MetS nor diabetes, 148 patients (26%) with 163 lesions had MetS without diabetes and 131 patients (23%) with 148 lesions had diabetes. Baseline angiographic parameters were comparable between the three groups. Clinically driven target lesion revascularization rates for controls, MetS and diabetics were 7.7%, 5.4% and 14.5%, respectively (p = 0.041). Mortality rates for the three groups were 4.2%, 10.1% and 15.3%, respectively (p = 0.042). There were also significant differences in stent thrombosis (ST) rates with 0.3% in controls, 0.6% in MetS and 6.1% in diabetics (p = 0.037). Annual mortality and ST rates for controls, patients with MetS and diabetic patients were 1.2%, 3.0% and 5.6% (p = 0.037) and 0.2%, 0.3% and 2.7% (p = 0.039), respectively. Late loss in-lesion was 0.19 ± 0.59 mm in controls, 0.17 ± 0.44 mm in patients with MetS/no diabetes and 0.46 ± 0.81 mm in diabetics (p < 0.001). Conclusion. During long-term follow up after implantation of SES in de novo coronary lesions, MetS without diabetes does not result in an increase in target lesion revascularization or ST rates compared with control patients. However, patients with MetS have a higher follow-up mortality rate compared to control patients.
J INVASIVE CARDIOL 2010;22:317–321
Key words: diabetes, drugs, metabolic syndrome, restenosis, stent
Metabolic syndrome (MetS) is rapidly increasing in frequency. Patients with MetS have an increased risk to develop coronary artery disease (CAD) as well as cardiovascular events.1,2 Even patients with MetS but no diabetes proved to have a higher prevalence of CAD, and the combination of both CAD and MetS has been associated with increased cardiovascular risks.3 Diabetes mellitus and insulin resistance have been shown to be strong independent predictors of restenosis after bare-metal stent (BMS) implantation.4–6 Even with the introduction of drug-eluting stents (DES), diabetes has remained a significant predictor of in-stent restenosis.7,8 The impact of MetS on restenosis and long-term clinical outcomes including stent thrombosis (ST) after percutaneous coronary intervention using sirolimus-eluting stents (SES) has not been well defined. Thus, the aim of this study was to examine the impact of MetS on clinical event rates during long-term follow up after implantation of SES.
This was a single-center study which included consecutive patients treated with the Cypher® SES (Cordis Corp. Miami Lakes, Florida).
Patients. A total of 563 patients with 629 de novo coronary lesions (< 50 mm lesion length, reference diameter < 3.5 mm) successfully treated with SES between June 2003 and December 2006 were prospectively enrolled in the study. Patients were considered eligible if they presented with angina pectoris, had a positive stress test or in whom both criteria were positive, and who had significant stenosis (> 50%) in a native coronary vessel. Patients were excluded if they had a bifurcation lesion, a left main lesion or an in-stent restenotic lesion. The study was approved by the ethical committee of the University Aachen.
Coronary intervention. Heparin was administered during the procedure according to standard practice. Aspirin (100 mg/day) and clopidogrel (300 mg loading dose) were started before the procedure. After the procedure, clopidogrel (75 mg/day) was administered in addition to aspirin for 6 months after elective stenting using a SES, and for 9–12 months after stenting for acute coronary syndromes. Glycoprotein IIb/IIIa inhibitors were given at the discretion of the operator. Cypher SES were available in lengths of 8–33 mm and diameters of 2.5–3.5 mm.
Follow-up protocol. Procedural success was defined as < 30% final diameter stenosis in the treated lesion and the absence of major clinical complications (in-hospital death, myocardial infarction [MI] or emergency coronary bypass surgery). All patients were followed for 41 ± 17 months after the procedure by telephone interviews for any major adverse cardiac event (MACE) defined as death, MI or need for target lesion revascularization. In addition, the occurrence of definite ST was determined based on clinical events and confirmed by coronary angiography. Baseline clinical demographics, in-hospital complications and the occurrence of death, MI, late recurrent coronary intervention and definite ST during follow up were verified by independent hospital chart review and source documentation or the records of family physicians. MI was defined as creatine-kinase (CKMB) at least 3 times the upper limit of normal. Clinical events were adjudicated by FV and KCK. Between 2003 and 2004, angiographic follow up was recommended in all PCI patients and was obtained in 80% of patients. Subsequently, hospital recommendations for follow-up angiography changed, resulting in drop in angiographic follow-up rates to 30%.
Quantitative coronary angiography. Baseline, post-procedural and follow-up coronary angiograms were digitally recorded and analyzed offline at the angiographic core laboratory of University Aachen using a validated quantitative angiographic system (CAAS II System; Pie Medical Imaging, Maastricht, The Netherlands) by experienced personnel unaware of the clinical status of the patients. The contrast-filled catheter tip was used as the calibration standard. All measurements were performed on cine angiograms recorded after the intracoronary administration of nitroglycerin. Quantitative measurements included reference diameter, lesion length and minimal luminal diameter in-lesion (defined as the in-stent segment plus proximal and distal 5 mm edge segments) and in-stent (without an adjacent edge segment). Late loss was calculated as the reduction in minimal luminal diameter from immediately after the procedure to follow up.
Study endpoints and definitions. The primary endpoint of the study was survival free of MACE. Secondary endpoints were survival free of need for revascularization of the target lesion because of narrowing of the lumen in the presence of symptoms or objective signs of ischemia, angiographic restenosis (in-segment stenosis > 50% on follow-up angiography) and definite ST (stent thrombosis is angiographically documented as complete occlusion or flow-limiting thrombus of previously successfully treated artery). ST episodes are reported as early events up to 30 days post stent implantation, late events from 30 days to 1 year and very late events more than 1 year post-stent implantation. Patients were categorized into three groups: 1) controls, no MetS and no diabetes; 2) MetS, MetS and no diabetes; and 3) diabetics, diabetes with or without MetS. The presence of MetS was analyzed considering the presence of the following criteria: 1) hypertension, defined as blood pressure of at least 130/85 mmHg or patient taking antihypertensive medication; 2) fasting glucose ≥ 110 mg/dl; 3) reduced high-density lipoprotein (HDL) cholesterol (< 40 mg/dl in men, < 50 mg/dl in women) or pharmacologic treatment for reduced HDL cholesterol; 4) a fasting triglyceride level > 1.7 mmol/L (150 mg/dl) or pharmacologic treatment for hypertriglyceridemia; and 5) central obesity (body mass index > 28.8 kg/m2). A body mass index > 28.8 kg/m2 was used as a substitute for a waist circumference ≥ 102 cm in men or ≥ 88 cm in women, as shown in a study of Scottish men and in the Women’s Health Study.9,10 Patients were considered to have MetS in the presence of three or more of these criteria according to the definition proposed by the American Heart Association in conjunction with the National Heart, Lung, and Blood Institute (AHA/NHLBI).11 Diabetes was defined as fasting glucose ≥ 126 mg/dl.
Statistical analysis. Statistical analysis was performed using SPSS version 12.0 (SPSS, Inc., Chicago, Illinois). Categorical data were compared using Pearson’s chi-square test and are presented as frequencies. Continuous data were compared using the Student’s t-test or analysis of variance as adequate and are presented as mean ± standard deviation. Post hoc analysis (with Bonferroni’s correction) was performed for multiple comparisons. To consider the different follow-up periods for SES patients, Kaplan-Meier curves for freedom from MACEs were analyzed. The impact of diabetes and MetS on freedom from MACE during the follow-up period was evaluated with the log-rank test. A p-value < 0.05 was considered statistically significant.
A total of 284 patients (51%) with 318 lesions were in the control group, 148 patients (26%) with 163 lesions had MetS and 132 patients (23%) with 148 lesions were diabetics. Baseline clinical characteristics are summarized in Table 1. Patients with MetS were more frequently male and had more frequent hypertension. The diabetics were older than the other patient groups.
Lesion characteristics for each of the three patient subgroups are shown in Table 2. Baseline angiographic parameters were comparable between the three groups with regard to lesion length, reference vessel diameter, minimal lesion diameter and lesion location.
Procedural data are provided in Table 2. There were no differences between the three groups with regard to stent length, stent diameter and the number of stents used per lesion.
Angiographic results. Follow-up angiography was performed for 294 patients with 329 lesions. One-hundred fifty control patients, 76 patients with MetS and 64 diabetics had angiographic follow up (Table 3). The frequency of repeat angiography was similar for the three groups (53.8%, 52.1% and 49.3%, respectively). The clinical and angiographic baseline characteristics of the patients with follow-up angiography were comparable to the total study group. In-lesion late loss was 0.19 ± 0.59 mm in the controls, 0.17 ± 0.44 mm in patients with MetS and 0.46 ± 0.81 mm in diabetics (p < 0.001). Similarly, in-stent late loss was significantly different between the three patient groups (Table 3). The binary in-lesion restenosis rate was higher in diabetics compared to nondiabetic patients. There were no differences in restenosis rates between the control patients and those with MetS.