Author + information
- Received February 12, 1998
- Revision received May 6, 1998
- Accepted May 20, 1998
- Published online September 1, 1998.
- Joseph De Gregorio, MDa,
- Yoshio Kobayashi, MDa,
- Remo Albiero, MDa,
- Bernhard Reimers, MDa,
- Carlo Di Mario, MD, FACCa,
- Leo Finci, MD, FACCa and
- Antonio Colombo, MD, FACCa,*
- ↵*Address for correspondence: Dr. Antonio Colombo, Centro Cuore Columbus via M. Buonarroti 48, 20145 Milan, Italy
Objectives. This study sought to compare the short- and long-term outcomes of elderly patients undergoing coronary artery stenting with those of younger patients and to determine the long-term clinical outcome and survival of elderly patients post stent implantation.
Background. Elderly patients undergoing coronary revascularization are considered a high-risk group. Few data exist that relate the results of stenting in treating coronary artery disease in the elderly population.
Methods. All elderly patients ≥75 years of age who underwent coronary artery stenting between March 1993 and July 1997 (n = 137) at our center were compared to the patients <75 who underwent coronary artery stenting during the same time period (n = 2,551). Long-term clinical follow-up and survival were determined for the elderly group.
Results. Elderly patients presented with lower ejection fractions (54% vs. 58%, p = 0.0001), more unstable angina (47% vs. 28%, p = 0.0001), and more multivessel disease (78% vs. 62%, p = 0.0001) than younger patients. These older patients had higher rates of procedure related complications including procedural myocardial infarction (MI) (2.9% vs. 1.7%, p = 0.2), emergency CABG (3.7% vs. 1.4%, p = 0.04), and death (2.2% vs. 0.12%, p = 0.0001). Angiographic follow-up, obtained in both groups, demonstrated significantly higher restenosis rates in the elderly versus younger patients (47% vs. 28%, p = 0.0007). Longer term clinical follow-up, which was obtained only in the elderly group, showed that at a mean follow-up period of 12 months post coronary stenting, elderly survival free from death, MI, revascularization and angina was 54% and that their overall survival was 91%. Subanalysis of the elderly patients who died showed much higher incidence of combined unstable angina (80%), prior MI (60%), lower ejection fraction (46%), multivessel disease (100%) and complex lesions (100%) than the overall group.
Conclusions. Elderly patients who undergo coronary artery stenting have significantly higher rates of procedural complications and worse six month outcomes than younger patients, especially those who present with combined unstable angina, history of MI, EF < 50%, multivessel disease and complex lesions. Overall survival in the elderly population at 12 months postcoronary artery stenting was 91% and event-free survival was 54%.
The elderly comprise the fastest growing segment of the population. In 1990, the U.S. census estimated that there were >31 million persons over the age of 65, 25% of which had reported symptomatic coronary artery disease. The number of elderly are expected to increase by 65% by the year 2020 (1).
Compared to the general population, elderly patients undergoing coronary revascularization have traditionally been more likely to present with more: complex lesions, unstable angina, comorbid conditions and lower ejection fractions (1–10). At least in part due to these facts elderly patients have traditionally had higher rates of procedure related death and complications when undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) (4–23). Despite these problems, the rates of PTCA and CABG among the elderly, between 1987 and 1990, increased by 55% and 18%, respectively.
With the advent of procedural modification, allowing the elimination of anticoagulation, coronary artery stenting has come to widespread use (24–27), including in the elderly. But do the advantages that stenting has afforded the general population translate to the elderly population with comparable procedure-related complications and long-term outcome? The present study was designed to investigate the impact of stenting in treating coronary artery disease in our elderly population ≥75 years of age and examines the period of time from March 1993 through July 1997.
The study included 2,688 consecutive patients who underwent coronary artery stenting at the Centro Cuore Columbus, Milan, Italy, between March 30, 1993, and July 2, 1997. All patients treated with intracoronary stents during this time period were included in our analysis, divided into two cohort groups: 2,551 persons <75 years of age (younger cohort) and 137 persons ≥75 years of age (elderly cohort).
Stent implantation procedure
Before stent implantation procedure, all patients received aspirin 325 mg to 500 mg. A 10,000 unit bolus of heparin was given after sheath insertion; thereafter, heparin boluses were administered during the procedure as needed to maintain an activated clotting time ≥250 s. The Palmaz-Schatz stent was used in 42% of the lesions, the NIR stent in 12%, the AVE stents in 7% and the Gianturco-Roubin stent in 7%. In the remaining patients other types of slotted tube or coil stents were used. Stents were either hand crimped on a balloon or premounted on a delivery system. After stent deployment, further dilatations were performed using high-pressure balloon inflations (≥14 atm). Since April 1993 stents have been placed with the utilization of intravascular ultrasound in the majority of cases. With the introduction of intravascular ultrasound guided coronary stenting, patients who met optimal stenting criteria did not receive any heparin or oral anticoagulant agents after the procedure. Only 3.2% of patients <75 and 1.7% of patients ≥75 received any type of anticoagulation therapy during this time period (no patients received dextran or dipyridamole). Ticlopidine (250 mg twice daily) was given for a period of one month and aspirin (325 mg daily) continued indefinitely.
Indications for stenting and their definitions were performed as previously reported (27). The use of >1 stent per lesion or per patient was considered multiple stenting. Each stent was counted as one stent except the short Palmaz-Schatz stents and the 4 or 8 mm Micro stents, which were counted as half stents.
Coronary angiograms were obtained in a routine fashion. Patients received intracoronary isosorbide dinitrate before initial and postprocedural angiograms to achieve maximal vasodilatation. Vessel and lesion measurements were obtained using a computerized quantitative analysis system (QCA-CMS Version 3.0, MEDIS) according to previously described and validated edge detection algorithms using the catheter as the object of calibration (28). The following measurements were obtained both preintervention and poststent placement: reference vessel diameters, minimal lumen diameter, percent diameter stenosis and lesion length. Each stenotic segment was evaluated for the presence or absence of calcium and thrombus. Lesions were characterized according to the modified American Heart Association/American College of Cardiology classification (29).
Clinical follow-up was obtained when patients were seen at the outpatient clinic or by direct telephone interview. Adjunctive information was obtained from the referring physician. Event-free survival upon clinical follow-up was defined as free from death, myocardial infarction (MI), revascularization or angina. Survival curves were generated taking into account all elderly patients who underwent stent implantation and all related deaths from the time of stent implantation. Angina symptoms were characterized according to the Canadian Cardiovascular Society classification. For patients who had clinical events, clinical follow-up ended at the time of the event. Angiographic follow-up was routinely scheduled at 5 to 6 months postprocedure for all patients with a successful procedure who had had their procedure ≥5 months prior to this analysis and had not undergone CABG during this period. Restenosis was defined as ≥50% diameter stenosis by angiography on follow-up. Diffuse restenosis was defined as a restenotic lesion >10 mm in length (30,31).
Procedure successwas defined as ≤20% residual stenosis in the target lesion poststent implantation without the occurrence of myocardial infarction, urgent coronary artery bypass graft surgery or death. Complete revascularizationwas achieved when there was no residual stenosis ≥70% in any major coronary artery or their large branches unless a bypass graft fed the territory distal to a diseased segment. Clinical eventswere defined as death from any cause, coronary artery bypass surgery, myocardial infarction (Q wave or nonQ wave) repeat angioplasty and vascular complications. Q wave myocardial infarctionwas diagnosed when there were new pathologic Q waves on electrocardiogram accompanied by an elevation in creatinine kinase levels to twice the normal level. A non-Q wave myocardial infarctionwas diagnosed when an elevation of the creatinine kinase to twice normal levels occurred without the development of Q waves. Vascular complications were defined as the occurrence of pseudoaneurysm, bleeding or hematoma at the access site requiring transfusion, vascular repair or external compression. Other bleeding complicationswere defined as gastrointestinal, neurologic or any other significant bleed other than that of the access site. Stent restenosiswas defined as ≥50% diameter stenosis at the stented site or at the proximal or distal adjacent sites. Diffuse restenosiswas defined as a ≥50% luminal narrowing ≥10 mm in length; if shorter, the restenosis was defined as focal (32,33).
The primary clinical analysis consisted of a comparison between the two cohorts that were divided by age. Categorical variables are presented as absolute numbers (percent). Continuous variables are presented as mean values ± standard deviation. Differences between groups were evaluated by chi-square analysis for categorical data or the two-tailed Student ttest for continuous data. These differences were considered statistically significant at p value ≤0.05. The Kaplan-Meier method was used to generate a survival curve.
Baseline clinical and cardiovascular characteristics
These are shown for both cohort groups in Table 1. Average age of the younger group was 58 ± 2.9 years and 78 ± 9.0 years for the elderly group. There were significant differences in risk factors between the two groups with the elderly having a higher prevalence of hypertension (56% vs. 44%, p = 0.0006), and the younger group having a greater incidence of hypercholesterolemia (57% vs. 44%, p = 0.003), family history (44% vs. 29%, p = 0.0005), and smoking (65% vs. 44%, p = 0.0001). Left ventricular ejection fraction was significantly different (58.4% in the younger cohort vs. 54.4% in the older cohort, p = 0.0001). There were much higher rates of unstable angina in the elderly population (47% vs. 28%, p = 0.0001). The only major risk factor without a significant difference between the two groups was incidence of diabetes mellitus (13% vs. 12%).
Angiographic and procedural characteristics
Baseline angiographic and procedural characteristics are shown in Table 2. There was significantly more three vessel coronary disease present in the elderly patients (40% vs. 24%, p = 0.0001), and a greater proportion of combined type B2 and C type lesions (72% in the elderly vs. 65% in the younger, p = 0.09). Also, there were a higher proportion of calcified lesions in the elderly group (30% vs. 13%, p = 0.0001). Surprisingly, there were a larger number of total occlusions in the younger cohort (13% vs. 9%, p = 0.04). There was no significant difference between groups in angiographic mean reference diameter, lesion percent stenosis and lesion length.
Stent implant procedure characteristics
Procedural characteristics are seen in Table 3. Various stents were used in both patient populations; however, a stent summary shows that there is no significant difference between the two groups (p = 0.5). The Palmaz-Schatz and the NIR stent were the most commonly used during the course of this study. A combination of different stent types were used in 7.7% of the younger group and 9.4% of the older group (p = NS). There were some significant differences between the groups as to which arteries needed stenting. There were more LAD lesions stented in the younger group (46% vs. 34%, p = 0.0001) and more left main stenting in the elderly (1.5% vs. 7.3%, p = 0.0001). Frequency of the various lesion sites treated also differed, with more ostial lesions in the elderly (15% vs. 7%) and more proximal lesions in the younger cohort (p = 0.006). In accordance with the presence of more multivessel disease, there was more multivessel stenting in the elderly (44% vs. 27%, p = 0.0001). Overall number of stents per patient, final balloon size and maximal inflation pressure did not differ between groups. Final stent MLD was slightly greater in the elderly by 0.1 mm (p = 0.04). More rotablation was performed in the elderly group (23% vs. 9%, p = 0.0001), which goes along with the more calcified disease. Complete revascularization was more readily achieved in the younger group (56% vs. 31%, p = 0.008); however, procedure success did not differ significantly.
Primary clinical and angiographic events
These appear in Table 4. Thrombotic events and bleeding complications did not differ significantly between these groups. However, there were significantly more procedural complications in the elderly, including emergency coronary artery bypass grafting (CABG) (3.7% vs. 1.4%, p = 0.04) and procedural death (2.2% vs. 0.1%, p = 0.0001).
Angiographic follow-up was obtained in 73% of the <75-year-old cohort and in 66% of the ≥75-year-old cohort. Table 5shows the results of angiographic follow-up. Patients who had early events (within 5 months of procedure), such as procedural CABG or death, are excluded. Stent minimal lumen diameter (MLD) and percent stenosis were significantly worse in the elderly group (2 mm vs. 1.8 mm, p = 0.03 and 33% vs. 41%, p = 0.05). Restenosis rates were higher in the elderly (47% vs. 28%, p = 0.0007). Target lesion revascularization reflected the restenosis rates and were higher in the elderly (28% vs. 19%, p = 0.02).
Long-term clinical follow-up is reported only in the elderly population and was obtained in 97% of patients. The mean follow-up period was 12 months ranging from within 1 month of procedure in cases of early adverse events to 58 months poststenting. A Kaplan-Meier curve demonstrates survival rate in this group with 91% of patients being alive within the clinical follow-up period (Figure 1). The event-free survival rate in the elderly during this period was 54% with an incidence of recurrent angina, revascularization, MI or death in 46% of patients. Table 6depicts a subanalysis of elderly patients who died. There were 3 procedural deaths and 7 deaths in the follow-up period. Average age of these patients is 78.6 ± 3.7 with an 80% incidence of unstable angina and 60% incidence of prior MI in this subgroup. Average ejection fraction is 45.6%. All patients had multivessel disease and complex coronary lesions (B2 or C type). Of note is the fact that none of the elderly patients in this subgroup was diabetic.
Also of interest is that of the 10 elderly patients who had left main coronary artery stenting (8 being unprotected left main arteries) 7 patients had angiographic follow-up without restenosis. Of the remaining 3 patients, one had a procedural complication (this was a CABG; no other procedural complications occurred), one patient was lost to follow-up and for the final patient it was too early to obtain angiographic follow-up.
Revascularization in the elderly: CABG and PTCA
The majority of hospital admissions for cardiovascular disease involve the elderly population. When undergoing revascularization, this high-risk group has traditionally been reported to have an increased rate of procedure-related death, MI, bleeding complications and stroke versus younger patients (4–23). Despite this, rates of revascularization in this population have increased significantly since 1987 and several studies have shown improving trends in elderly patients undergoing revascularization. Also, patients ≥65 years of age postacute MI have a 30-day mortality of 21% and a one-year mortality of 34% (32)and studies such as Thrombolysis In Myocardial Infarction (TIMI) IIIB have shown improved outcome, at least in the short term, in elderly patients undergoing aggressive revascularization when presenting with unstable angina or non-Q w MI (33).
Recent studies regarding CABG in the elderly report procedural mortality rates of 6% to 10% (1–5,15,16)and 30-day mortality of 8% to 14% (1,5). Roach et al. have shown that patients over age 70 who underwent coronary bypass surgery had a cumulative incidence of stroke of 12% (15). This in turn was associated with a 5- to 10-fold increase in mortality. There has also been extensive work examining the results of angioplasty in the elderly. These reports exhibit procedural mortality rates of 1.4% to 10% and an emergency CABG rate ranging from 0.7% to 7%. Thompson et al. (6)have shown a changing trend towards lower complication rates in the elderly treated with PTCA between 1980 and 1992 with procedural mortality decreasing to 1.4% and emergency CABG down to 0.7%.
Since the time of these early reports, the use of high-pressure balloon inflations, intravascular ultrasound guidance and better antiplatelet agents have contributed to the removal of anticoagulation, bringing stenting to widespread use (24–26). Although there is an extensive amount of published information regarding PTCA and CABG in the elderly, there are limited data available with regards to stenting in this population.
Coronary artery stenting in the elderly
Early studies of stenting and standard anticoagulation reported significant vascular complications at a rate of about 16% (34). Vascular complications were even more pronounced in the elderly; Elliot et al. showed a 45% vascular complication rate for patients >70 years of age who underwent stenting (22). Removal of anticoagulation has tempered this situation. A recent analysis that compared vascular complications from two different time periods (1991–1994 vs. 1994–1995) in patients >70 years of age who underwent Palmaz-Schatz stent implantation showed an incidence of vascular complications of 13.2% and 0%, respectively (35). Our data, with the new antiplatelet regimen, show a vascular complication rate of 0.8% in the population ≥75 and 0.9% in the patients <75 (p = NS). In this regard we have been able to reduce what was a severe problem, and to equalize the complication rate between older and younger patients.
However, there are a number of problems that continue to exist with revascularization in the elderly population. Our results show a promising trend toward better outcome in this fragile group, but a significant difference continues to exist between results obtained in the older versus younger patients, both in short- and long-term outcome. There was a significantly higher rate of procedure-related CABG and death along with substantially more procedural myocardial infarction in the ≥75 cohort (Table 4). Also of concern in treating this elderly group is the fact that there is a much higher rate of angiographic restenosis (47% vs. 28%, p = 0.0007). The TLR coincides with these results and has a concurrent distribution of events (28% vs. 19%, p = 0.02). Significant differences in the elderly population that help to explain their inferior outcome include the fact that they present with lower ejection fractions, more unstable angina and a higher angina class (Table 1). It has also been documented in previous studies that older patients present with more comorbid disease (5). The angiographic lesion characteristics we found also provide an explanation for higher complication rates and worse long-term outcome. There were more ostial lesions (15% vs. 7%, p = 0.006), three-vessel disease, calcified lesions and complex lesions (72% combined B2 and C type lesions vs. 65%, p = 0.09) in the elderly compared to the younger patients. Treatment strategies did not differ greatly as average balloon size and inflation pressure were similar (Table 3). Likewise, angiographic reference diameters and lesion percent stenosis showed no significant difference (Table 2). The approach differed on the basis of adjunctive procedures and complete revascularization. More rotablation was performed in the older group (23% vs. 9%, p = 0.0001) reflecting the fact that there was a proportionately higher number of calcified lesions (30% vs. 13%, p = 0.0001). Complete revascularization was more often achieved in the younger cohort although procedure success was not significantly different (Table 3). This reflects the fact that there was more three-vessel disease in the elderly (Table 2), making complete revascularization more difficult to achieve.
These clinical and angiographic characteristics in the elderly may also help explain the fact that long-term clinical follow-up shows a high incidence of adverse events. However, despite the higher rates of procedural complications, restenosis and low rate of freedom from events, the elderly group displays a good overall survival rate on clinical follow-up post stent implantation (Figure 1).
Elderly patients with poorest outcome
A subgroup analysis of the 10 elderly patients who died during or following stent implantation yields some interesting results. Three deaths were considered procedural; five deaths were within 1 month, with one death at 3 months and one death at 5 months. Therefore, 8 of the 10 deaths were within 1 month of stent implant and all deaths were within 5 months of procedure. It seems that if an elderly patient survived this critical period, he could expect long-term survival. The findings that set this group apart from the rest of the elderly population and portend poorer outcome include some of the classic risk factors. Five risk factors including unstable angina, prior MI, lower ejection fraction (<50%), multivessel disease and complex lesions were all much more prominent in this subgroup compared to the rest of the elderly. In fact, 8 of the 10 patients who died had ≥4 of these risk factors; the two remaining patients had either two or three of these characteristics. The total number of elderly patients with ≥4 of these risk factors is 26; therefore, the mortality for an elderly patient with these characteristics undergoing coronary artery stenting was 31%.
Limitations of the study
There are several limitations to the present study. It is a retrospective study and therefore inherently contains all the disadvantages of such a comparative analysis. In making any direct comparisons, lesion characteristics and number do differ in some respects between the elderly and younger populations and treatment strategies towards these lesions vary slightly. However, this is part of what we wished to demonstrate; that the elderly do present with more difficult lesions and that this plays some role in their poorer outcome. Angiographic follow-up in the elderly population was slightly lower than in the younger group (66% vs. 73%, p = NS); however, a 66% follow-up in this fragile population is a realistic target. Validity of the observed angiographic restenosis rates in the elderly population is supported by the strong correlation between these results, the TLR and the clinical event rate (restenosis 47%, TLR 28% and clinical follow-up event rate of 46%). This study does represent a relatively large nonselected experience from a single center, which provides some insight into the difficulties that exist with revascularization and stent implantation in the elderly population.
Elderly patients who undergo coronary artery stenting have significantly more procedural complications and worse 6-month outcome than younger patients. This is in part due to presentation of the elderly with significantly more three-vessel coronary artery disease, unstable angina, complex lesions and lower ejection fractions. The subgroup of elderly patients with poorest outcome had significantly higher rates of these combined risk factors, including prior MI. Overall long-term survival after coronary artery stenting in the elderly is 91% at 1 year but event free survival is only 54%. There have been considerable gains made in the past 10 years in the treatment of coronary artery disease in the elderly; however, despite technological advances with improvements in revascularization equipment, increased operator experience, procedural modifications and stent technology, procedural complications and adverse cardiac events during follow-up are significantly higher in older patients. Further improvements are necessary to optimize the results in this high-risk group.
- coronary artery bypass grafting
- ejection fraction
- intravascular ultrasound
- minimal lumen diameter
- myocardial infarction
- percutaneous transluminal coronary angioplasty
- quantitative coronary angiography
- Received February 12, 1998.
- Revision received May 6, 1998.
- Accepted May 20, 1998.
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