Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Stents in Patients With ST-Segment Elevation Myocardial Infarction

3-Year Results of the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) Trial

Methods

Results

Long-term clinical follow-up

Complete datasets were available in 157 of 160 (98%) patients in the SES group and in 156 of 160 (97.5%) patients in the BMS group.

The 3-year outcome is outlined in Table 2.The SES implantation showed a reduction of 40.5% in MACE risk compared with BMS (12.7% vs. 21%, p = 0.034). The cumulative 3-year survival rates free from MACE were 87% and 79% for the SES group and the BMS group, respectively (p < 0.05) (Fig. 1A).Results of the SES were, with regard to concerns overall secondary end points, better than those of BMS: TLR 7% versus 13.5% (p = 0.048) with 48% of risk reduction; TVR 8% versus 16% (p = 0.027) with 50% of risk reduction; and TVF 11.5% versus 20.5% (p = 0.028) with 44% of risk reduction. The lower incidence of adverse events in the SES group was due primarily to fewer TLRs. The greatest benefit was achieved in the first year of follow-up with no significant differences between 12 and 36 months. The cumulative 3-year survival rates free from TLR (Fig. 1B) and TVF (Fig. 1C) were 93% and 89.5% for the SES group and 86.5% and 79.5% for the BMS group, respectively (p < 0.05). There was no statistical difference in terms of death, recurrent MI, or ST between the 2 groups.

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Figure 1

Actuarial Rates of Survival Free From MACE, TLR, and TVR

Kaplan-Meier estimates of survival free from major adverse cardiovascular events (MACE) (A), target lesion revascularization (TLR) (B), and target vessel failure (TVF) (C)among patients treated with a sirolimus-eluting stent (SES) or bare-metal stent (BMS). The MACE, TLR and TVF free survival was significantly higher in the SES group than the BMS group (p < 0.05).

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Table 2

Clinical Outcome at 3 Years

We revealed, compared with the previous assessment of clinical outcome at 1-year, 12 new MACE, 7 in the SES group (Table 3).In this group 2 more patients died—1 from gastric cancer, and 1 from pulmonary embolism. One patient presented with nonfatal recurrent MI, and 4 patients underwent TLR—3 underwent re-PCI for a focal in-stent restenosis in 2 cases and ST in 1 case. The fourth patient underwent CABG for in-stent restenosis and progression of the left main coronary artery disease. In the BMS group, another patient died from lung cancer, and another had nonfatal MI. Another 3 patients underwent percutaneous TLR—1 for focal in-stent restenosis, 1 for diffuse in-stent restenosis, and 1 for ST.

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Table 3

Clinical Events During 12- to 36-Month Follow-Up

The mean duration of dual antiplatelet therapy was 375 ± 12 days and 369 ± 35 days for the SES and BMS groups, respectively (p = NS). The cumulative incidence of death for all causes and nonfatal MI was comparable in the 2 groups starting from the time of clopidogrel discontinuation at 3-year follow-up.

Discussion

The present study demonstrates that SES implantation is better, in terms of MACE, TLR, TVR, and TVF, compared with BMS in patients with STEMI at 3-year follow-up. The greatest benefit was achieved in the first year and maintained at 3 years.

The main proven benefit of DES versus BMS is the reduction of restenosis in various clinical and angiographic settings (10), especially in high-risk patients such as those presenting with STEMI (6–8,11). Restenosis is not a benign clinical occurrence, because it has been associated with increased risk of death and MI (12). However, randomized data on long-term safety and efficacy of DES in the STEMI setting are still lacking. In the STRATEGY (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction) trial (7) it has been demonstrated that the cumulative incidence of MACE was constantly lower in the tirofiban + SES group compared with Abciximab + BMS group due primarily to the different rate of TVR without any significant increase in the death rate, recurrent MI, or ST at 2-year clinical follow-up. Our study confirms these findings and extends the clinical follow-up to 3 years. The SES treatment was associated with a 40.5% risk reduction of MACE with a cumulative incidence of MACE-free survival of 87% compared with 79% in the BMS group, even if the SES group had longer and smaller implanted stents. In agreement with our results, a recent meta-analysis of randomized trials comparing the short- and the long-term clinical benefit of SES versus BMS showed a significant reduction in TVR with no significant difference in ST incidence in SES patients at 1-, 2-, and 3-year follow-up (13). In contrast to our results, a recent nonrandomized study, comparing 3-year clinical outcome of SES, paclitaxel-eluting stent, and BMS in patients with STEMI, showed that SES was more efficacious in triggering a decrease in TVR compared with paclitaxel-eluting stent or BMS only at 1-year follow-up. This advantage was lost at 3-year follow-up, partly explained by the occurrence of late ST in the SES group (14). In a recent multinational registry of patients with STEMI, who had undergone PCI with DES or BMS, a similar mortality was reported for the first 6 months after discharge but was significantly higher from 6 months to 2 years for DES patients, compared with BMS patients (15). Indeed, primary stenting has been recognized as an independent predictor of late stent malapposition in BMS (16) as well as in DES patients (17), with an incidence 2- to 3-fold higher compared with elective stenting. Potential mechanisms of late adverse events are still controversial. Thrombus displacement by the stent struts with abluminal thrombus resolution in the long-term might lead to a major incidence of stent malapposition and might account for the higher rates of early and late ST (18). Moreover, a large thrombus burden can affect stent-based drug-elution and significantly alter vessel wall drug levels and potentially the efficacy, thus explaining the higher rate of in-stent restenosis in patients with STEMI compared with that in those with other clinical settings (19). By contrast, recent data suggest that late adverse events are caused mainly by a ruptured plaque in the adjacent vessel outside the stent and are not strictly stent-related (20,21). Another risk factor for late adverse events seems to be premature discontinuation of dual antiplatelet therapy (22). In a large observational study, DES ST was observed in approximately 30% of patients who prematurely discontinued antiplatelet therapy (23). Much controversy still exists concerning the duration of dual antiplatelet therapy in STEMI patients. Some authors concluded that, because the cardiovascular outcomes improved with more robust or prolonged antiplatelet therapy in patients with acute coronary syndromes or prior history of ischemic events or PCI, it should be recommended for >1 year—perhaps indefinitely—in all patients receiving DES (24).

In contrast with these findings, in our study, the rate of definite ST was 1.9% in the SES group and 1.3% in the BMS group (p = NS), whereas the cumulative incidence of death and nonfatal recurrent MI was comparable in the 2 groups starting from the time of clopidogrel discontinuation. In agreement with our data it has been reported that, although withdrawal of clopidogrel was associated with an increased mortality risk, it does not depend upon the type of stent implanted (25). Moreover, a recent collaborative network meta-analysis (26) focused on safety and effectiveness of DES and BMS in high-risk patients such as those with diabetes mellitus. Results suggested that the previously reported increased risk of death, associated with SES, was probably due to the short duration of dual antiplatelet therapy in early studies but was no longer found in trials in which dual antiplatelet therapy was given for >6 months.

Conclusions

The present study demonstrates that SES are associated with a significant reduction of MACE, TLR, TVR, and TVF compared with BMS at 3-year follow-up after stenting for STEMI. The SES seems to be as safe as BMS, without evidence of any increased risk of death, recurrent MI, or ST, including no incremental risks after withdrawal of dual antiplatelet therapy.