In the past few years, the use of drug-eluting stents (DES) has had a significant impact on the practice of interventional cardiology. The introduction of DES followed the same course as any newly introduced technique, with the initial period of enthusiasm subsequently followed by a period of extensive criticism. Currently, better equipment and understanding of the needs of prolonged dual-antiplatelet therapy with DES have changed percutaneous coronary intervention (PCI). However, most of the published literature on stents pertains to the pre-DES era. Given the lack of long-term follow-up data on DES, careful review of the literature becomes necessary before making any recommendations or guidelines. Randomized trials have proven the superiority of stents over balloon angioplasty as the primary revascularization strategy for acute ST-segment elevation myocardial infarction (STEMI)
1,2 due to a reduced need for repeat intervention in the target vessel for up to 12 months.
3DES have been traditionally considered superior to bare-metal stents (BMS) because they further reduce the need for reintervention in the target vessel,
4however, randomized trials have reported conflicting efficacy results. The initial approval of DES from the U.S. Food and Drug Administration was based on evidence consisting of randomized, controlled trials (RCTs) enrolling patients with stable coronary artery disease (CAD) and noncomplex, single, de novo coronary artery lesions. These RCTs have suggested that there is no difference in the overall rates of death and MI among patients treated with DES or BMS, perhaps because of the offsetting risks/benefits of DES.
5–7 On the contrary, DES are currently being used “off label” in high-risk patients with more complex lesions and concerns have arisen about the performance of DES in the “real world.” The single center study by Palmieri et al, which is published in the current issue of the Journal, addressed the above issue by comparing the efficacy of DES versus BMS in an unselected “real-life” patient population with acute STEMI.
8 A total of 453 consecutive patients (241 males, 113 females) presenting with acute STEMI and undergoing primary or rescue PCI of the infarct-related artery within 24 hours of onset of symptoms were studied. One hundred seventy-six patients received BMS and 277 patients received DES (134 paclitaxel-eluting stents [PES]; 143 sirolimus-eluting stents [SES]) in the infarct-related artery. In addition to antiplatelet therapy with aspirin 100 mg/day, patients treated with BMS were prescribed at least 1 month of clopidogrel (75 mg/day) or ticlopidine (500 mg/day), while those treated with DES were administered clopidogrel for 6 months to 1 year. The procedural characteristics, 30-day, 12-, 18- and 26-month outcomes of the two cohorts were compared. At 26-month follow up, DES use was associated with a statistically significant decrease in major adverse cardiac events (MACE) (relative risk reduction [RRR] 35%; p = 0.01) and target lesion revascularization (TLR) (RRR 64%; p = 0.009). The overall incidence at 26 months for stent thrombosis was 5.6% in the BMS group and 3.2% in the DES group (p = 0.12, statistically insignificant). The authors went further and compared the subgroups with PES and SES, but did not find any significant differences in terms of MACE or new revascularization procedures. MACE, with no consensus definition, are the most commonly used composite endpoints in cardiovascular research. In the present study, MACE was defined as the composite of all-cause death, MI and new revascularization (PCI or CABG). There was a 35% overall reduction in the rate of adverse events at 26-month follow up in the DES group as compared with the BMS group. This reduced cumulative risk of MACE in the DES group, however, was attributed to a significant reduction in TLR and not to death (RRR 33%; p = 0.16) or MI (RRR 50%; p = 0.12). It has been argued that whenever a trial combines “hard” but infrequent endpoints such as death and MI, with “soft” but more frequent endpoints such as reintervention, these less important outcomes often drive the effect of therapy due to increased frequency.
9 The findings of this study are in concordance with previously published randomized trials evaluating the role of DES in acute STEMI. Spaulding et al performed a multicenter, prospectively randomized trial showing a decrease in the rate of TVR (5.6% vs 13.4%; p 10 In the SESAMI trial, Menichelli et al demonstrated that SES are superior to BMS, reducing the incidence of binary restenosis by 56%, TLR by 61%, TVR by 62%, adverse cardiac events by 59%, and target vessel failure by 53% at 1 year.
6 However, the prospective, single-blind, randomized PASSION trial by Laarman et al failed to demonstrate a statistically significant difference (8.8% vs 12.8%, respectively; p = 0.09) in the incidence of MACE at 1 year with the use of PES versus BMS in acute STEMI.
11 Recently, a meta-analysis of DES versus BMS compared the results from randomized, controlled trials and observational studies.
12 In RCTs, treatment with DES was associated with no detectable differences in death or MI, with a significant 55% reduction in TVR. In observational studies, the nonrandomized use of DES versus BMS was associated with significant 22% and 13% reductions in all-cause mortality and MI, respectively, and a significant 46% reduction in TVR. The observed differences between these two analyses demonstrate that reliance on neither should be absolute. Although RCTs reduce the influence of confounders and represent the purest comparison by minimizing treatment selection bias, observational studies may be more generalizable and minimize enrollment bias, but are more subject to confounding with respect to patient selection and duration of antiplatelet therapy in DES versus BMS groups. The present study being a nonrandomized observational study truly demonstrates the “real-life” situation as noted by the investigators. BMS were mostly used in older patients (mean age: 65 ± 0.89 years) at higher risk of bleeding with a lower probability of being compliant with the antiplatelet therapy. On the contrary, DES were chosen in younger patients (mean age: 62 ± 0.71 years; p = 0.01), diabetics (20% vs. 9%; p 13,14 Whether this is also true for late stent thrombosis is unclear; however, caution must be exercised, given the lack of comparative data and the difference in the duration of dual-antiplatelet therapy between devices. In conclusion, this is an important study highlighting the feasibility and safety of DES in patients with acute STEMI in the real world. The findings of this study show that DES significantly reduce the need for new revascularization in these patients, without any evidence of additional risks at 2-year follow up. The investigators also appropriately noted that the improved long-term outcomes could be due to prolonged combined antiplatelet therapy in patients with DES. However, costs must be evaluated carefully, as DES are significantly more expensive, and the need for longer courses of dual-antiplatelet therapy further adds cost to the DES cohort. Whether these increased costs are offset by the lower rate of MACE needs evaluation by these authors and others. Current guidelines suggest selected use of DES, however, most centers report DES use far exceeding guideline recommendations. Given the spiraling health care costs, further research into the appropriate use of DES is mandatory.
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From the Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, California.
The authors report no conflicts of interest regarding the content herein.
Address for correspondence: Matthew J. Budoff, MD, Associate Professor of Medicine, Los Angeles Biomedical Research Institute, 1124 West Carson Street, Torrance, CA 90502. E-mail: mbudoff@labiomed.org
