Long-Term Outcomes Comparison of Different Types of DES in Elderly Patients from a Real-World Experience

ABSTRACT: Objective. We sought to evaluate the impact on long-term clinical outcomes of different types of drug-eluting stents (DES) in elderly patients. Background. Elderly patients constitute a fast-growing portion of cardiovascular patients, however, they are not adequately represented in clinical trials. Moreover, few data comparing different type of DES in elderly patients are available. Methods. From a total of 2,330 consecutive patients treated at our institution with DES, we selected 207 elderly patients (≥ 75 years of age) who underwent, from May 2002 to December 2006, sirolimus-eluting stent (SES group, 116 patients [pts], 56%) or paclitaxel-eluting stent (PES group, 91 pts, 43.9%) implantation. We evaluated the 24-month incidence of major adverse cardiac events (MACE). Results. Higher rates of hypertension (78.4% vs. 90.1%; p = 0.01), diabetes (37.9 vs. 45.1; p = 0.01) and previous coronary artery bypass grafts (10.3% vs. 19.4%; p = 0.04) in the PES group were observed, whereas in the SES group, there were more smokers (26.6% vs. 12.1%; p = 0.007) and a higher incidence of previous myocardial infarction (MI) (50% vs. 35.2%; p = 0.02). Procedural success and in-hospital MACE were similar in both groups. At follow up, there was a higher incidence of MACE (22.4% vs. 10.9%; p = 0.04) and target lesion revascularization (7.1% vs. 3.0%; p = 0.02) in the SES group compared to the PES group. The incidence of cardiac death and MI were comparable between the two groups, as well as the rate of stent thrombosis. After adjustment for clinical and angiographic characteristics, no significant differences in outcomes were observed between SES and PES. Conclusions. In this real-word experience, no significant differences were found in the safety and efficacy profiles between SES and PES use in elderly patients. Key words: Drug-eluting stent; elderly; paclitaxel-eluting stent; sirolimus-eluting stent J INVASIVE CARDIOL 2009;21:330–333 Patients enrolled in coronary intervention trials are not always representative of patients in clinical practice.1,2 In fact, cardiovascular disease is a leading cause of morbidity and mortality in the elderly and these patients are increasingly referred for percutaneous coronary intervention (PCI),3,4 but to date, there are no specific guidelines or trials examining this patient subset. Currently, PCI in the elderly is feasible and effective due to the development of new interventional techniques.5–8 If in the past bare-metal stents (BMS) were considered the reference stents for these patients, recent studies have shown that DES results are better than those of BMS.9–12 Yet, there is a paucity of data on the safety and efficacy profile of different types of DES in elderly patients. We sought to evaluate the difference between the use of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) in elderly patients undergoing elective PCI. Methods Study population. Patients were identified from the Ferrarotto Hospital DES Registry, which is an ongoing single-center clinical data collection study. We examined data from all consecutive patients undergoing PCI with implantation of at least 1 DES at the Ferrarotto Hospital in Catania, Italy. The DES was either a Cypher™ SES (Cordis Corp., Miami Lakes, Florida) or a Taxus® PES (Boston Scientific Corp., Natick, Massachusetts). In a computerized database, baseline demographic and clinical characteristics, angiographic data and information about medical therapy were prospectively recorded at the time of initial PCI. For the purpose of this analysis, patients undergoing PCI with either SES or PES from May 2002 to December 2006 were included. Medication and PCI. PCI and intracoronary stent implantation were performed using standard percutaneous techniques.13 The decision to implant a SES or PES was left to the discretion of the operator and was mainly based on the availability of stent sizes. All patients undergoing PCI were put on aspirin, which was maintained indefinitely. Thienopyridine treatment was recommended for at least 6 months. Informed consent to undergo the interventional procedure and to allow clinical follow up was obtained from all patients. Endpoint, definitions and follow up. After discharge, patients were followed by scheduled clinical visits or telephone interviews at 1, 6, 12 months and every 6 months after the first year. Medical records of patients hospitalized during the follow-up period were obtained in order to validate and adjudicate adverse events. We concentrated primarily on the major adverse cardiac events (MACE) defined as the composite of cardiac death, nonfatal myocardial infarction (MI) requiring hospitalization, or any repeat target vessel revascularization (TVR) evaluated both in-hospital and at follow up. Secondary endpoints were the components of MACE, target lesion revascularization (TLR) and stent thrombosis. Cardiovascular death was considered to be any death with a demonstrable cardiovascular cause or any death that was not clearly attributable to a noncardiovascular cause. MI was defined as the occurrence of ischemic symptoms in the presence of electrocardiographic (ECG) changes and by a rise in biochemical markers of myocardial necrosis. TVR included any clinically driven target vessel reintervention or non-target lesion reintervention by either PCI or coronary artery bypass graft (CABG) surgery. Stent thrombosis (ST) was defined as an acute coronary syndrome with angiographic documentation of either vessel occlusion or thrombus within or adjacent to a previously successfully stented vessel. According to the Academic Research Consortium (ARC) classification, ST was defined as definite (symptoms suggestive of an acute coronary syndrome and angiographic or pathologic confirmation of ST), probable (unexplained death within 30 days after the procedure or target vessel-related MI without angiographic confirmation of ST), or possible (any unexplained death after 30 days). ST was also categorized according to the timing of the event into: intraprocedural, subacute (from the end of the procedure to 30 days) and late ST (> 30 days).14 Long-term follow up was completed in December 2007. Statistical analysis. All data were processed using the Statistical Package for Social Sciences, version 15 (SPSS, Inc., Chicago, Illinois). Continuous variables were reported as mean ± standard deviation (SD) and compared using the independent sample Student’s t-test. Discrete variables are reported as frequencies (percentage) and compared using the chi-square or Fisher’s exact tests, as appropriate. A p-value of Results Patient characteristics and angiographic characteristics. From a total of 2,330 patients undergoing PCI from May 2002 to December 2006, 207 patients (8.8%) were ≥ 75 years of age. This cohort was divided into two groups: 116 patients treated with SES implantation (56%) and 91 patients treated with PES implantation (44%). Patients’ basic characteristics revealed a higher prevalence of hypertension (78.4% vs. 90.1%; p = 0.01), diabetes (37.9 vs. 45.1; p = 0.01) and previous CABG (10.3% vs. 19.4%; p = 0.04) in the PES group, whereas the SES group showed more smokers (26.6% vs. 12.1%; p 12 months was performed in 68% of the eligible population. The mean long-term follow up was 23 ± 10 months (range 1–51 months). At follow up, in the SES group there was a higher incidence of cumulative MACE (22.4% vs. 10.9%; p = 0.04) and TLR (7.1 vs 3.0; p = 0.02). TVR (9.1 vs. 4.7; p = 0.2), cardiac death (7.1 vs. 3.0; p = 0.4), and MI (3.0 vs. 1.5; p = 0.4) showed higher rates in the SES group (Table 4). Safety profile analyses showed an incidence of definite/probable/possible stent thrombosis (according to the ARC definition) in patients treated with SES comparable with patients treated with PES (4.3% vs. 3.3%; p = 0.5) (Table 5). After adjustment for clinical and angiographic characteristics, no significant differences were observed between SES and PES in the efficacy and safety profiles (Table 6). Discussion In the last few years the increasing number of elderly patients affected by cardiac ischemia puts us in front of a difficult therapeutic choice, especially if we consider the lack of specific randomized trials and guidelines.2 Previous studies on elderly patients undergoing PCI and CABG report less successful revascularization and more adverse outcomes.15 Moreover, previous studies8–10 have demonstrated worse early and long-term outcomes in elderly patients who underwent PCI compared with younger patients. The prevalence of comorbidities and complex coronary artery disease in the elderly is significantly greater before PCI and even greater when compared with younger patients, and is associated with lower procedural success and a higher incidence of complications.3,4 Improved stent designs and PCI techniques and new platelet inhibitors and antithrombotic agents have led to a remarkable improvement in outcomes after PCI in the elderly.5 Nevertheless, elderly patients still remain a high-risk population with a life expectancy far inferior than the rest of the population, but that is comparable with the population of the same age.10 BMS have been the most frequently used stents in elderly patients, even though they are associated with a higher risk of in-stent restenosis, because they do not require prolonged dual antiplatelet therapy and, compared to DES, they show a lower risk of stent thrombosis.14 In fact, recent studies11–13 comparing BMS and DES have shown encouraging results regarding the use of DES in elderly patients, even if published studies about the use of DES in the elderly are limited. In a recent study, Vlaar et al10 reported the outcomes of 366 octogenarians compared with 2,087 younger patients treated with DES, indicating that the life expectancy of the group of patients ≥ 80 years of age was similar to the expected survival rate in the general population. In the DESIRE registry,11 the stent thrombosis rate of patients > 80 years of age was similar to that of patients 70–80 years of age, and even those aged 75 years of age. No data exist on SES versus PES in the elderly that clarify whether there is an actual benefit in using one or the other kind of stent. In the general population,16 SES were found to be superior to PES because of a significant reduction of the risk of reintervention and ST. The risk of death was not significantly different between the SES and PES patients, but there was a trend toward a higher risk of MI with PES, especially 1 year post procedure. In our study, elderly patients treated with SES showed a higher incidence of MACE at 24-month follow up, with a worse trend in TLR when compared with those treated with PES. However, after the adjustment for different variables, a statistically significant difference was no longer evident. Another relevant observation from our study is that the percentage of in-hospital and follow-up MACE was similar to that of the published literature. Boudu et al5 reported a 9.8% in-hospital MACE rate, while the mortality rate at the 51-month mean follow-up period was reported to be 32%. Just as in the DESIRE registry, MACE at 1 year, in ultra-octogenarian patients, is equal to 6% with a cardiac-related death rate equal to 5.4%. Thus our data, although limited, encourage the use of DES in the elderly population — regardless of stent type — because of the more angiographically complex disease in this cohort, keeping in mind that the patient’s associated comorbidities must be evaluated. Randomized studies are needed to provide a wider experience of the use of DES in the elderly, with more in-depth information on the risk of bleeding, which might be an issue in this particular patient population. Study limitations. This study has two primary limitations. First, it was a retrospective, single-center analysis, and second, the sample size is relatively small and is thus underpowered to address any statistical conclusions on safety outcomes. Conclusions In this real-world experience, no significant differences were found in the safety and efficacy profiles between SES and PES use in elderly patients. From the Department of Cardiology, Ferrarotto Hospital-University of Catania, Catania, Italy. The authors report no conflicts of interest regarding the content herein. Manuscript submitted February 24, 2009, provisional acceptance given March 2, 2009, final version accepted March 13, 2009. Address for correspondence: Alessandra Sanfilippo, MD, Ferrarotto Hospital, Cardiology, via Citelli 6, Catania, 95124, Italy. E-mail: alesanfi@libero.it or contact Dr. Capodanno at: dcapodanno@gmail.com

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