Primary percutaneous coronary intervention (PCI) has been shown to be superior to thrombolytic therapy in the treatment of ST-elevation myocardial infarction (STEMI).1 The routine use of bare metal stents (BMS) in this setting is superior to balloon angioplasty.2–4 Nevertheless, the rates of target vessel revascularization (TVR) or restenosis after BMS implantation in patients with acute myocardial infarction (AMI) are still relatively high. A series of randomized trials, observational studies and meta-analysis of clinical trials had shown that drug-eluting stents (DES) are associated with a significant reduction in TVR or restenosis in patients with STEMI compared with BMS.5–15 At present, primary PCI with stent implantation has become the treatment of choice for most patients with STEMI. However, safety concerns of the potentially higher risk of stent thrombosis and death with DES have emerged.16,17 In fact, only a few studies have reported the long-term outcomes of DES as compared to BMS in patients with STEMI. The purpose of this study was to evaluate the long-term outcomes of DES and compare them with BMS in patients with STEMI undergoing primary PCI.
A total of 191 patients with acute STEMI undergoing primary PCI from Jan. 2005 to Dec. 2007 were enrolled. Individuals eligible for enrolment were patients presenting with STEMI who fulfilled all the following inclusion criteria: (1) chest pain for >30 minutes, (2) ST-segment elevation of ≥1 mm in ≥2 contiguous electrocardiograph leads, or with new left bundle-branch block, (3) hospital admission within 12 hours from symptoms onset, or between 12 and 24 hours from symptoms onset but with ischemic chest pain worsened. Exclusion criteria were cardiogenic shock.
Procedures and post-intervention medications
All procedures were performed according to the standard interventional technique via a femoral or radial approach. Patients received DES or BMS implantation in the infarction related artery according to the physician's discretion. Chewed aspirin 300 mg was given in the emergency department, followed by 100 mg orally daily. A clopidogrel loading dose of either 300 or 600 mg was administered before catheterization, followed by 75 mg orally daily for at least 6 months. Dual antiplatelet therapy was recommended for at least 1 year.
Definitions and follow-up
The primary outcome was the occurrence of major adverse cardiac events (MACE); defined as the composite of all-cause death, nonfatal myocardial infarction (MI), TVR, or stent thrombosis. Secondary outcomes included all separate components of primary outcomes. MI was defined as ischemic chest pain with either a new ST segment and T wave changes or recurrent elevation of creatine kinase which is more than 2 times the upper limit of normal range with an increase in creatine kinase-MB. TVR was defined as any reintervention (PCI or coronary artery bypass grafting) in the same vessel treated at the index procedure driven by ischemia and documentation of a lesions >50% diameter stenosis. Definite stent thrombosis was defined as angiographically defined thrombosis with TIMI flow grade 0 or 1 or the presence of flow-limiting thrombus of the previously stented infarction related artery. Clinical follow-up was performed at our outpatient clinic or by telephone interview.
Continuous variables were expressed as mean ± standard deviation and were compared with the Student's t test. Categorical variables (presented as numbers and percentages) were compared using the chi-square test. Logistic regression was used for analysis of predictors for MACE. All tests were 2-sided and statistical significance was defined as P <0.05. The SAS software version 8.2 (Institute Inc., USA) was used for data analysis.
A total of 191 patients with acute STEMI undergoing primary PCI were enrolled, including 154 males and 37 females. Patients received DES (n=83) or BMS (n=108) implantation in the infarction related artery according to the physician's discretion. A total of 241 stents were implanted; 114 DES and 127 BMS. The baseline characteristics between the DES and BMS groups were well matched, except that the patients were older, had more myocardial damage and worse left ventricular systolic function while they received stents with shorter length and bigger diameter in the BMS group compared with DES group (Table 1).
Clinical follow-up outcomes
Clinical follow-up duration was three years ((41.7±16.1) months). MACE occurred in 20 patients during three years clinical follow-up; 16 patients in the BMS group (5 patients with cardiac death, 3 patients with non-cardiac death, 1 patient with AMI, 6 patients with TVR, 1 patient with subacute (24 hours to 30 days) stent thrombosis, 1 patient with late (31 to 365 days) stent thrombosis, and there was 1 non-cardiac death patient with TVR. MACE occurred in 4 patients in the DES group (3 patients with cardiac death and 1 patient with very late (>365 days) stent thrombosis) (Table 2). Logistic regression analysis showed that the left ventricular ejection fraction (LVEF) was an independent predictor for MACE in the follow-up period (P=0.0301).
Incidence of MACE in DES group and BMS group
As shown in Table 2, there was no significant difference in all-cause mortality (3.61% vs. 7.41%, P=0.2647), the incidence of myocardial infarction (0 vs. 0.93%, P=0.379) and the incidence of stent thrombosis (1.20% vs. 1.85%, P=0.727) between the DES group and BMS group. The incidence of MACE was significantly lower in the DES group compared to the BMS group (4.82% vs. 14.81%, P=0.0253). The rate of TVR was also lower in the DES group (0 vs. 5.56%, P=0.029).
There was one cardiac death and one case of very late stent thrombosis in the sirolimus eluting stent (SES) subgroup while there were two cardiac deaths in the paclitaxel-eluting stent (PES) subgroup. In the DES group, there was no significant difference in the incidence of MACE between SES (n=73) and PES (n=10) subgroups (2.74% vs. 20.00%, P >0.05).
In the present study, MACE occurred in 20 patients during the three year clinical follow-up. There was no significant difference in all-cause mortality, the incidence of myocardial infarction and stent thrombosis between the DES group and the BMS group. The incidence of MACE was lower in the DES group which may be due to the lower rate of TVR. This finding suggested that DES can significantly reduce the need for revascularization in patients with acute STEMI, without an increase in the incidence of death or myocardial infarction. Use of DES significantly reduced the incidence of MACE compared with BMS during 3-year follow-up.
Randomized trials, observational studies and meta-analysis of clinical trials have shown that DES compared with BMS can cause a significant reduction in restenosis or TVR in patients with STEMI.5–15 In the TYPHOON study, Spaulding et al5 found that the rate of the primary target-vessel failure at 1 year after the procedure (target-vessel-related death, recurrent myocardial infarction, or target-vessel revascularization) was significantly lower in the SES group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This reduction was driven by a decrease in the rate of target-vessel revascularization (5.6% and 13.4% respectively, P <0.001). However, there was no significant difference between the two groups in the rate of death, reinfarction or stent thrombosis. There are also many other studies which showed similar results.6–15
Our results are similar to the above mentioned studies which were mainly carried out in western populations and indicated that DES significantly reduce the need for revascularzation in patients with STEMI, without increasing the incidence of death or myocardial infarction. The current study also showed that use of DES was not associated with an increased risk of stent thrombosis during 3-year follow-up, although the rate of stent thrombosis was relatively low (1.20% in DES vs. 1.85% in BMS) in these patients.
However, there are also some studies with outcomes16–18 different from the above mentioned studies,5–15 so safety concerns have emerged about the potential risk of stent thrombosis and death with DES. Lagerqvist et al17 found that DES implantations were associated with an increased rate of death compared with BMS in a study in 19 771 cases. This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and the composite of death or myocardial infarction was 0.5 to 1.0 percentage points higher per year in the DES group. A recent study19 showed that very-late stent thrombosis was more common in SES (n=508) and PES (n=576) groups than in the BMS (n=450) group (2.4% vs. 0.9% vs. 0.4% respectively, P=0.02). However, there were no significant differences between the stent types for all-cause mortality and all cause mortality/myocardial infarction at 6-year follow-up. This study indicated that SES and PES have a beneficial effect on safety and efficacy outcome compared with BMS in terms of decreased TVR. Although the occurrence of more very late stent thrombosis in SES and PES patients remains a safety concern, this did not influence the safety end points which were all cause mortality and the composite end point of all-cause mortality and MI.
The BASKET trial20 suggested that after the discontinuation of clopidogrel, the benefit of DES in reducing TVR is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis. There was one case in our current study that developed very-late stent thrombosis 2 weeks after discontinuation of 2 years of clopidogrel. American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the management of patients with ST-elevating myocardial infarction21 also indicated that continuation of clopidogrel or prasugrel beyond 15 months may be considered in patients undergoing DES placement.
This study is a single-center and nonrandomized study with a relatively small sample size. The difference of the baseline data may influence the results of this study although we have made statistical adjustments.
In summary, our finding suggested that DES significantly reduced the need for revascularization in patients with acute STEMI, without an increase in the incidence of death or myocardial infarction. Use of DES significantly decreased the incidence of MACE compared with BMS during 3-year follow-up.
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