Mid-term angiographic benefit of sirolimus-eluting stents compared with paclitaxel-eluting stents in patients with acute myocardial infarction
- Cheol Ung Choi, a,
- Seung-Woon Rha, a,
, 
, - Kang-Yin Chen, a,
- Zhe Jin, a,
- Yoshiyasu Minami, a,
- Seung Yong Shin, a,
- Jin Oh Na, a,
- Soon Yong Suh, b,
- Hong Euy Lim, a,
- Jin Won Kim, a,
- Eung Ju Kim, a,
- Chang Gyu Park, a,
- Hong Seog Seo, a,
- Dong Joo Oh, a
- a Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea
- b Cardiovascular Center, Konkuk University Hospital, Seoul, Republic of Korea
Summary
Background
We compared angiographic and clinical outcomes among different drug-eluting stents (DESs) in Korean acute myocardial infarction (AMI) patients.
Methods
A total of 109 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) with either sirolimus-eluting (SES, n = 56 pts) or paclitaxel-eluting stents (PES, n = 53 pts) were enrolled from August 2004 to December 2006. The angiographic outcomes at 6 months and clinical outcomes at 1 year were compared between the two groups.
Results
Baseline clinical and procedural characteristics were similar between the two groups. At 6 months, the rate of binary restenosis was 17.0% in the PES group compared with 3.6% in the SES group (p = 0.026). Percent restenosis was 24.9 ± 28.6% in the PES group compared with 11.2 ± 17.6% in the SES group (p = 0.004). Length of restenosis segment was 3.21 ± 9.02 mm in the PES group compared with 0.89 ± 2.38 mm in the SES group (p = 0.048). Late loss was 0.73 ± 0.89 mm in the PES group compared with 0.28 ± 0.37 mm in the SES group (p = 0.001). However, there were no differences in clinical outcomes at 1 year including mortality, myocardial infarction, repeat PCI, and major cardiac adverse events between two groups.
Conclusion
SES implantation in patients with AMI was associated with reduction in angiographic restenosis at 6 months compared with PES, however, these angiographic benefits were not translated into better clinical outcomes in real world clinical practice.
Keywords
- Drug-eluting stents;
- Sirolimus-eluting stents;
- Paclitaxel-eluting stents;
- Acute myocardial infarction
1. Introduction
Drug-eluting stents (DESs) have been rapidly accepted by the interventional community and are currently used in 80% of percutaneous coronary interventions (PCI) performed in the USA [1]. Several randomized trials have reported that DESs (sirolimus-eluting stents, SES; paclitaxel-eluting stents, PES) had a reduced incidence of restenosis and need for revascularization over 6–12 month follow-up compared with bare metal stents (BMSs) [2] and [3]. Therefore, SES and PES have been used more and more in patients with ST-segment elevation myocardial infarction (STEMI) [4] and [5]. Recent studies have reported that SES was superior to BMSs in decreasing the need for repeat revascularization in patients with STEMI at 1 year[4] and [6]. A number of randomized comparative studies between SES and PES have been performed [7],[8], [9] and [10]. However, to our knowledge, there are few studies about comparisons between SES and PES in patients with AMI. This study was designed to compare the clinical and angiographic outcomes between SES and PES, in patients with AMI.
2. Methods
2.1. Subjects and study design
The study was conducted at the department of cardiology of Korea University Guro Hospital, Seoul, Korea. Subjects were patients with AMI [STEMI or non-(N)STEMI] who underwent PCI and DES implantation (SES or PES) between August 2004 and December 2006. At 6 months after PCI, we compared the clinical and angiographic outcomes of SES and PES. All patients gave written informed consent. Although not randomized, our study represents consecutive cases that were exclusively treated with either SES or PES and stents were selected one after the other in different time periods and irrespective of clinical setting.
2.2. Stenting procedures
Before stent implantation, patients were premedicated with aspirin (200 mg), clopidogrel (loading dose 300 or 600 mg), and enoxaparin (1 mg/kg) SC. At the beginning of the intervention, unfractinated heparin bolus of 100 U/kg was administered after sheath insertion, and supplemental doses were then given to maintain an activated clotting time of >300 s. Stents were deployed with or without predilation according to standard techniques. Postdilatation was performed in selected patients to avoid stent underexpansion. Intravascular ultrasound was used in some cases if necessary. After stent implantation, aspirin (100 mg/day) was prescribed indefinitely and clopidogrel (75 mg/day) was administered for at least 12 months. Quantitative coronary angiogram (QCA) was performed at baseline (at the angiography before index PCI) and immediately after stent deployment.
2.3. Study definitions
Binary restenosis was defined as >50% diameter stenosis. Major adverse cardiac events (MACEs) were defined as death from any cause, Q wave myocardial infarction, target vessel revascularization (TVR), and target lesion revascularization (TLR). Q wave myocardial infarction was defined as development of Q waves in >2 contiguous leads with postprocedural creatine kinase MB isoenzyme levels elevated above normal. TVR was defined as emergency or elective coronary artery bypass graft (CABG) or repeat PCI in the target vessel. TLR was defined as emergency or elective CABG or repeat PCI in the target lesion. Diabetes mellitus was defined as fasting blood glucose concentration ≥126 mg/dl or taking diabetes medications. Hypertension (HTN) was defined as repeated measurements of ≥140 mmHg systolic blood pressure or ≥90 mmHg diastolic blood pressure or previous diagnosis. Smoking status was classified as non-smoker and smoker. Dyslipidemia was defined in cases meeting any one of the following criteria: total cholesterol >200 mg/dl; triglyceride >150 mg/dl; high-density lipoprotein cholesterol <40 mg/dl; or low-density lipoprotein cholesterol >100 mg/dl.
2.4. Follow up
Complete clinical outcomes were examined at 1 year after the PCI. All MACEs occurring cumulatively at 1 year after stent implantation were examined. Angiographic follow up was scheduled at 6 months after index PCI. QCA was also performed at the follow up angiography.
2.5. Statistical methods
Continuous variables are presented as means ± SD. Categorical variables are expressed as percentages. Comparisons of continuous variables between SES and PES groups were performed with Student t-test. Comparisons of categorical variables between SES and PES groups were performed with a Chi-square test. To identify the predictors of binary restenosis in patients with AMI, multivariate logistic regression analysis was used. Univariate variables with p < 0.20 were entered into the multivariate logistic models. A p < 0.05 was considered statistically significant. Statistical analysis was performed using the SPSS 10.0 software package (SPSS Inc., Chicago, IL, USA).
3. Results
3.1. Patients and procedural characteristics
In total, 109 consecutive AMI patients with 109 culprit lesions were treated with 56 SES and 53 PES. Among the 56 patients in the SES group, 13 had multivessel coronary artery disease and 16 DESs (SES, 11; PES, 5) were implanted. Among the 53 patients in the PES group, 11 had multivessel coronary artery disease and 20 DESs (SES, 5; PES, 15) were implanted. Baseline clinical characteristics of subjects were similar between the two groups (Table 1). Procedural characteristics of subjects are presented in Table 2. There were more lesions of left anterior descending coronary artery (LAD) in the group with SES, while lesions of right coronary artery (RCA) were more frequent in the group with PES.
- Table 1.
Baseline clinical characteristics.
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SES, sirolimus-eluting stents; PES, paclitaxel-eluting stents; STEMI, ST-segment elevation myocardial infarction; EF, ejection fraction; CABG, coronary artery bypass graft.
- Table 2.
Baseline angiographic and procedural characteristics.
-
SES, sirolimus-eluting stents; PES, paclitaxel-eluting stents; MI, myocardial infarction; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery; PCI, percutaneous coronary intervention; RVD, reference vessel diameter; MLD, minimal luminal diameter.
3.2. Clinical outcomes at 1 year and angiographic outcomes at 6 months
Table 3 shows the clinical outcomes at 1 year and angiographic outcomes at 6 months. At 6 months, the PES group showed higher rates of binary restenosis, percent restenosis, longer length of restenosis segments, and more late loss compared with the SES group. However, there were no differences in clinical outcomes at 1 year including mortality, myocardial infarction, repeat PCI, and MACEs between the two groups.
- Table 3.
Clinical outcomes at 1 year and angiographic outcomes at 6 months.
-
SES, sirolimus-eluting stents; PES, paclitaxel-eluting stents; MLD, minimal luminal diameter; MI, myocardial infarction; TLR, target lesion revascularization; TVR, target vessel revascularization; MACEs, major cardiac adverse events.
3.3. Logistic regression analysis for predictors of 6-month binary stenosis
Univariate logistic regression analysis revealed that binary restenosis could be predicted by the type of DES [PES vs. SES, odds ratio (OR) 5.523, 95% confidence interval 1.134–26.893; p = 0.034], but could not be predicted by other clinical and angiographic characteristics (Table 4). In the multivariate model of logistic regression analysis, after the adjustment for smoking, HTN, bifurcation lesion, and type of DES, only the type of DES was significantly associated with binary restensois (PES vs. SES, OR 5.241, 95% confidence interval 1.031–26.655; p = 0.046) (Table 4).
- Table 4.
Logistic regression analysis for predictors of 6-month binary stenosis.
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OR, odds ratio; CI, confidence interval; STEMI, ST-segment elevation myocardial infarction; PTCA, percutaneous transcatheter coronary angioplasty; PES, paclitaxel-eluting stent; RVD, reference vessel diameter; PCI, percutaneous coronary intervention; DS, diameter stenosis; MLD, minimal luminal diameter.
4. Discussion
The main findings of our study are as follows. First, the use of SES during primary PCI in patients with AMI was associated with a reduction in the incidence of binary restenosis, reduction in percent restenosis, reduction in the length of restenosis segment, and reduction in late loss at 6 months compared with the use of PES. Second, in the multivariate model of logistic regression analysis, only the type of DES (PES) was significantly associated with binary restensois at 6 months. Third, however, the overall incidence of stent thrombosis and major clinical outcomes including death, MI, repeat PCI, and MACEs up to 6 months were not different between the SES and PES groups, suggesting the angiographic benefit of SES shown at 6 months did not translate into more favorable clinical outcomes up to 1 year compared with the PES group. We thought that there were several good explanations for this result. First, subsequent mortality rate after AMI depends primarily on final infarct size and left ventricular dysfunction as well as from occurrence of no-reflow phenomenon which are all independent from the type of stent used. In the present study, no estimates of infarct size and follow up left ventricular dysfunction were provided. Second, even “angiographically” significant restenosis of the target vessel may not impair distal coronary blood flow to a reduced amount of viable myocardium and may not result in recurrent ischemia or symptoms in post-MI patients. However, we did not evaluate the amount of viable myocardium. Third, the number of enrolled patients was too small to detect differences in 1-year clinical outcomes between the two types of DES. Thus, we thought that it was hard to expect that the reduced restenosis rate with SES group which had lower lumen loss compared with the PES group could translate into better clinical outcome.
A previous study reported that SES implantation for the treatment of de novo coronary lesions was associated with a profoundly reduced 6-month restenosis rate [11]. Thereafter, the efficacy and safety of DESs to treat coronary artery stenosis in stable patients has been reported in trials for non-complex lesions[12], [13], [14] and [15]. A number of randomized comparative studies between SES and PES have been performed [8], [9], [10] and [16]. Katritsis et al. reported that in patients, including those with AMI, there were no significant differences in MACEs and angiographic outcomes between SES and PES [16]. According to a comparison study between SES and PES in patients with AMI, there were no differences in MACE-free survival and rate of reintervention for restenosis at 1-year follow up [17]. However this study also showed that a trend to worse outcome was seen in the patients treated with PES compared with those with SES [17]. In our study, all patients underwent repeat coronary angiography at 6 months after PCI, but in the above study[17], repeat coronary angiography was clinically driven by symptoms or signs of ischemia. Therefore, we think that our study can show more exact results of angiographic outcomes.
In the present study, we found that the type of DES used was an independent predictor of restenosis and PES was significantly associated with binary restensois compared with SES. In 3 randomized studies, angiographic restenosis was significantly lower with SES compared with PES [8], [18] and [19]. Several possible mechanisms for this difference are as follows: (1) differences in pharmacological action between sirolimus and paclitaxel; (2) drug-release kinetics; (3) pattern of drug distribution in the arterial wall; and (4) stent characteristics [15].
Our study has some limitations. First, the number of enrolled patients is too small to detect differences in 1-year clinical outcomes between two types of DES and did not include zotarolimus-eluting stents (ZES). However, the significance of our study is that we performed follow up coronary angiogram for all patients at 6 months after PCI and there was the 6-month angiographic benefit of SES compared with PES. Further large, randomized, controlled studies with long-term follow up comparing efficacy and safety of the three different DESs, including ZES, in AMI patients undergoing PCI will be needed to reach the final conclusion. Secondly, we analyzed only 1-year clinical and 6-month angiographic outcomes, but did not compare long-term outcomes between SES and PES. Third, our cohort included patients not randomly assigned to a given DES type, and this study lacks the comparative power of specifically designed trials on the relative merits of SES and PES.
In conclusion, SES implantation in patients with AMI was associated with reduction in angiographic restenosis at 6 months compared with PES, however, these angiographic benefits could not be translated into better clinical outcomes in real world clinical practice. We think that further long-term follow up and large well randomized, controlled studies comparing SES and PES in AMI patients are needed.
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