CORRESPONDENCE: RESEARCH CORRESPONDENCE
A Randomized Comparison of Sirolimus- Versus Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus2-Year Clinical Outcomes of the DES-DIABETES Trial
Seung-Whan Lee, MD, PhD,
Seong-Wook Park, MD, PhD, FACC*,
Young-Hak Kim, MD, PhD,
Sung-Cheol Yun, PhD,
Duk-Woo Park, MD, PhD,
Cheol Whan Lee, MD, PhD,
Myeong-Ki Hong, MD, PhD,
Kyoung-Suk Rhee, MD, PhD,
Jei Keon Chae, MD, PhD,
Jae-Ki Ko, MD, PhD,
Jae-Hyeong Park, MD, PhD,
Jae-Hwan Lee, MD, PhD,
Si Wan Choi, MD,
Jin-Ok Jeong, MD, PhD,
In-Whan Seong, MD, PhD,
Yoon Haeng Cho, MD, PhD,
Nae-Hee Lee, MD, PhD,
June Hong Kim, MD, PhD,
Kook-Jin Chun, MD,
Hyun-Sook Kim, MD, PhD and
Seung-Jung Park, MD, PhD, FACC
* Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea (Email: swpark{at}amc.seoul.kr).
To the Editor:
The presence of diabetes mellitus has been associated with an increased risk of restenosis and unfavorable clinical outcomes in the era of bare-metal stents (BMS) or drug-eluting stents (DES). Previous studies found sirolimus-eluting stents (SES) to have greater efficacy than paclitaxel-eluting stents (PES) in diabetic patients for limited follow-up duration, and we previously performed a randomized, multicenter, prospective study showing that SES was superior to PES in reducing angiographic restenosis and 9-month adverse clinical outcomes (DES-DIABETES [Drug-Eluting Stent in patients with DIABETES mellitus] trial) (1). However, the long-term effectiveness of SES over PES remains controversial. To compare the long-term effectiveness of SES and PES in patients with diabetes mellitus, we evaluated the 2-year clinical outcomes, including stent thrombosis, target vessel revascularization (TVR), and major adverse cardiac events (MACE), including death, myocardial infarction (MI), and target lesion revascularization (TLR), of the patients included in the DES-DIABETES trial.
A minimum 24-month follow-up was performed in all living patients (Table 1). Three deaths (2 cardiac, 1 noncardiac) occurred in PES patients and none in SES patients. The 2 cardiac deaths were because of nontarget vessel MI and the noncardiac death was from gastric cancer. Myocardial infarction occurred in 1 SES patient and 2 PES patients. During 24 months, 2 stent thromboses (1 acute, 1 very late) occurred in SES group during dual antiplatelet therapy and none in PES group. At 2 years, the rates of TLR (3.5% vs. 11.0%, hazard ratio [HR]: 0.30; 95% confidence interval [CI]: 0.13 to 0.71; p = 0.006) and TVR (5.5% vs. 12.0%, HR: 0.39; 95% CI: 0.18 to 0.82; p = 0.014) were significantly lower in the SES than in the PES group. Clinically driven TLR (3.0% vs. 9.0%, p = 0.012) and TVR (4.0% vs. 10.5%, p = 0.012) rates were also significantly lower in the SES than in the PES group. Major adverse cardiac events were significantly lower in the SES than in the PES group (3.5% vs. 12.5%; HR: 0.27; 95% CI: 0.11 to 0.61; p = 0.002), as was the composite of death, MI, or TVR (5.5% vs. 14.0%, p = 0.004). On multivariate analysis, independent predictors of 2-year TLR were SES (HR: 0.28; 95% CI: 0.12 to 0.65; p = 0.003) and post-procedural minimal lumen diameter (HR: 0.36; 95% CI: 0.17 to 0.75; p = 0.006). Independent predictors of 2-year MACE were SES (HR: 0.24; 95% CI: 0.11 to 0.57; p = 0.001) and post-procedural minimal lumen diameter (HR: 0.35; 95% CI: 0.18 to 0.71; p = 0.003).
In the present study, we found the sustained benefit of SES over PES in the risks of 2-year TLR and MACE. The previous 2-year report from a registry (2) and a subgroup analysis of randomized trial (3) comparing the efficacy of SES and PES showed inconsistent findings in diabetic patients. Two-year registry study showed no difference of PES over SES in terms of TVR and MACE (3), whereas the subgroup analysis of randomized trial (3) reported that SES reduced MACE by 47% (14.8% vs. 25.8%; HR: 0.52; p = 0.05) and TLR by 61% (7.4% vs. 17.2%; HR: 0.39; p = 0.03) compared with PES at 2 years. The previous 2 studies have limitations of a nonrandomized study or subgroup analysis of randomized trial not dedicated to diabetic patients. In contrast, our study, which was prospective, multicenter, randomized, and dedicated to diabetic patients, demonstrated that SES maintained a reduction in TLR and MACE at 2 years compared with PES. This finding was supported by multivariate analysis showing that SES was an independent predictor of TLR and MACE. Moreover, a meta-analysis of 16 trials showed that SES significantly reduced the risk of reintervention compared with PES during mean follow-up periods ranging from 9 to 37 months in a broad population (4). Our results demonstrate that the benefits of SES can be extrapolated to diabetic patients.
In this study, there was no difference in the incidence of death and MI between SES and PES group. These findings are consistent with a network meta-analysis of 38 trials showing that SES, PES, and BMS were of comparative efficacy in risks of death, or the combined end point of death or MI, in both diabetics and nondiabetic patients for up to 4 years (5). In previous 2-year follow-up studies (2,3), the death (8.3% to 13.3% for SES and 10.8% to 11.5% for PES) and MI rate (1.9% to 5.1% for SES and 3.4% to 6.5% for PES) were greater than in our study. This finding may be partly explained by the inclusion of high-risk populations and different duration of clopidogrel use compared with our study. The longer administration of clopidogrel (>9 months) after DES or BMS reduced death or MI in diabetic patients (6). In present study, majority of the patients took clopidogrel for >9 months (81% of study population) with no significant difference in the duration of clopidogrel use between SES and PES patients (491 ± 377 days vs. 567 ± 393 days, p = 0.081). Optimal duration of clopidogrel use after DES implantation in diabetic patients should be determined in the future.
Recently published data reported that late stent thrombosis occurred steadily, with a constant rate of 0.6% per year, for up to 3 years after DES implantation. The 2-year incidence of stent thrombosis in diabetic patients in previous studies was 2.8% to 4.4% of SES patients and 2.4% to 2.6% of PES patients (2,3). In our study, none of the PES patients and only 2 SES patients (2 of 200, 1.0%) suffered from stent thrombosis (1 acute, 1 very late). This discrepancy in the incidence of stent thrombosis may have resulted from the differences in study design, inclusion criteria, definition of stent thrombosis, and duration of clopidogrel use.
In conclusion, SES implantation significantly reduced 2-year risks of TLR and MACE compared with PES implantation in diabetic patients. The use of SES with a larger post-procedural minimal lumen diameter improved the 2-year clinical outcomes in diabetic patients. Late stent thrombosis occurred only in 1 patient (0.25% of overall study population) during 2-year follow-up with prolonged use of clopidogrel, which suggests that extended use of clopidogrel after DES implantation in diabetic patients may be beneficial to reduce long-term adverse clinical outcomes.
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Footnotes
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Please note: Supported by the Cardiovascular Research Foundation (Korea) and a grant from the Korean Ministry of Health & Welfare as part of the Korea Health 21 Research & Development Project (0412-CR02-0704-0001).
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References
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1. Lee SW, Park SW, Kim YH, et al. A randomized comparison of sirolimus- versus paclitaxel-eluting stent implantation in patients with diabetes mellitus J Am Coll Cardiol 2008;52:727-733.[Abstract/Free Full Text]2. Daemen J, Garcia-Garcia HM, Kukreja N, et al. The long-term value of sirolimus- and paclitaxel-eluting stents over bare metal stents in patients with diabetes mellitus Eur Heart J 2007;28:26-32.[Abstract/Free Full Text] 3. Billinger M, Beutler J, Taghetchian KR, et al. Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients Eur Heart J 2008;29:718-725.[Abstract/Free Full Text] 4. Schömig A, Dibra A, Windecker S, et al. A meta-analysis of 16 randomized trials of sirolimus-eluting stents versus paclitaxel-eluting stents in patients with coronary artery disease J Am Coll Cardiol 2007;50:1373-1380.[Abstract/Free Full Text] 5. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis Lancet 2007;370:937-948.[CrossRef][Web of Science][Medline] 6. Brar SS, Kim J, Brar SK, et al. Long-term outcomes by clopidogrel duration and stent type in a diabetic population with de novo coronary artery lesions J Am Coll Cardiol 2008;51:2220-2227.[Abstract/Free Full Text]
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