Author + information
- Received April 12, 2000
- Revision received October 16, 2000
- Accepted November 17, 2000
- Published online March 1, 2001.
- Manish S Chauhan, MD∗,‡,* (, )
- Richard E Kuntz, MD, MSc†,‡,
- Kalon K.L Ho, MD, MSc, FACC∗,‡,
- David J Cohen, MD, MSc∗,
- Jeffrey J Popma, MD, FACC†,
- Joseph P Carrozza Jr, MD, FACC∗,
- Donald S Baim, MD, FACC† and
- Donald E Cutlip, MD, FACC‡
- ↵*Reprint requests and correspondence: Dr. Manish S. Chauhan, Interventional Cardiology Section, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215
The study compared the safety and efficacy of coronary artery stenting in aged and nonaged patients and identified predictors of adverse clinical outcomes.
Limited data are available on the outcomes of stenting in the aged (≥80 years) compared to nonaged patients.
The study was a pooled analysis of 6,186 patients who underwent coronary artery stenting in six recent multicenter trials. A clinical events committee adjudicated clinical end points, and quantitative angiography was performed by an independent core laboratory.
There were 301 (4.9%) aged patients (≥80 years). Compared to nonaged patients, aged patients had a higher prevalence of multivessel disease (16.5% vs. 9.6%, p = 0.001), unstable angina (50.8% vs. 42.1%, p = 0.003), moderate to severe target lesion calcification (30.4% vs. 15.3%, p = 0.001) and smaller reference vessel diameter (2.90 mm vs. 2.98 mm, p = 0.004). Procedural success rate (97.4% vs. 98.5%, p = 0.14) was similar in the two groups. In-hospital mortality (1.33% vs. 0.10%, p = 0.001), bleeding complications (4.98% vs. 1.00%, p < 0.001) and one-year mortality (5.65% vs. 1.41%, p < 0.001) were significantly higher for the aged patients. Clinical restenosis was similar for the two groups (11.19% vs. 11.93%, p = 0.78). Advanced age, diabetes, prior myocardial infarction and presence of three-vessel disease were independent predictors of long-term mortality.
Coronary artery stenting can be performed safely in patients ≥80 years of age, with excellent acute results and a low rate of clinical restenosis, albeit with higher incidences of in-hospital and long-term mortality, and vascular and bleeding complications compared to nonaged patients.
The aged (≥80 years) form the most rapidly growing segment of the U.S. population (1). Because the prevalence of coronary artery disease is higher in older patients, more of them are presenting for percutaneous coronary interventions (PCIs). These patients are more likely to have multivessel coronary artery disease and heavy calcification of the vessels, as well as other co-morbid conditions that place them at a higher risk for peri-procedural complications (2–4). At the same time, the use of coronary stents is steadily increasing to include high-risk indications, including older patients, and this currently constitutes over 60% of all coronary interventional procedures.
Earlier studies have reported a low rate of procedure success (<50% diameter stenosis without death, myocardial infarction [MI], or emergent bypass surgery) and high rates of major complications in older patients undergoing balloon angioplasty, including up to 8.4% 30-day mortality and 14% incidence of MI (2–14). In addition, older age has previously been reported to be a predictor of in-hospital mortality, as well as major ischemic and vascular complications in various small single-center angioplasty and stent studies. Data on the safety, efficacy and clinical outcomes of coronary stenting in the aged using modern deployment techniques and newer stent designs are limited.
The purpose of this study was to assess the success and safety of coronary artery stenting in the aged compared to the nonaged and to identify predictors of adverse outcomes using prospectively collected data from a large cohort of patients from recent multicenter clinical trials.
Patients enrolled in six recent major clinical trials of coronary stenting, between September 1995 and March 1999, formed the cohort for this analysis. These included four randomized trials comparing new stent designs (MultiLink, NIR, AVE Micro II, Bard XT) with the Palmaz-Schatz stent, Crossflex stent registry and the Stent Antithrombotic Regimen Study (STARS) trial (aspirin only and aspirin plus Coumadin groups were excluded), which compared three antithrombotic regimens following successful Palmaz-Schatz coronary stenting (15–21). All these trials had similar inclusion and exclusion criteria. In general, patients were to have focal (<20 mm) lesions with 50% to 99% diameter stenosis in a vessel, with visually estimated reference diameter >3 mm, that could be covered by one to two stents. Patients with recent preprocedural MI or left ventricular ejection fraction <30% were excluded from the trials. All trials were coordinated by the Cardiovascular Data Analysis Center (CDAC, Boston, Massachusetts). Primary data as well as quantitative angiographic data (using CMS-GFT algorithm) for each of these trials were collected prospectively and entered in separate databases at the CDAC using Microsoft Access 2.0. Following data cleaning and electronic validation of data entry for each study database, standard data tables were generated and then combined into a pooled database with unique patient identification.
Study population and stenting protocol
All patients treated within the six clinical trials who received at least one coronary stent and who were treated with aspirin and ticlopidine following the stent procedure were eligible for this analysis. The pooled data set included 6,186 patients who underwent stenting of 6,219 target lesions. The stenting protocol for each study included routine high-pressure postdilation with recommended balloon: artery ratios of 1.1–1.2. Aspirin 325 mg daily and ticlopidine 250 mg twice daily for four weeks formed the standard postprocedure antithrombotic regimen. Use of Gp (glycoprotein) IIb/IIIa inhibitors was discouraged in all of the studies, but they could be used at the discretion of the investigator and accounted for only 7.6% of patients overall. All patients were followed at prespecified points for 9 to 12 months in the individual trials, and a subgroup of patients had routine angiographic follow-up at 6 to 9 months.
Myocardial infarction (MI)included either Q-wave MI (QMI) (defined as presence of new regional pathologic Q-waves as reported by the blinded electrocardiogram [ECG] core laboratory) or non-QMI (defined as CK-MB [creatine kinase, MB fraction] values greater than three times normal or total CK more than two times the upper limit of normal for each respective clinical site, in the absence of new Q-waves). Vascular complicationsincluded access site-related hematoma >4 cm, pseudoaneurysm, atrioventricular (AV) fistula, retroperitoneal bleed or vascular surgical repair. Bleeding complicationswere reported as any procedure-related blood loss requiring transfusion. Stent thrombosiswas defined as angiographic documentation of stent occlusion, sudden unexplained death within 30 days of the stenting procedure when the stent was not known to be patent, recurrent MI in the target vessel territory, or urgent target lesion revascularization (TLR). Either TLR or TVR (target vessel revascularization) required the presence of clinical or functional evidence of ischemia and >50% stenosis by quantitative coronary angiography (QCA) or the presence of a restenotic lesion >70% by QCA in the absence of documented ischemia. An independent Clinical Events Committee (CEC), blinded to the treatment assignment for randomized cohorts, adjudicated all clinical events.
Justification for pooled analyses
These prospective studies, which were performed at the same clinical sites over a narrow time period, had nearly identical inclusion criteria, stenting protocols, similar case report forms with entry in standard databases, clinical follow-up and end point definitions as well as event adjudication by the same CEC for each study. Furthermore, the same angiographic core laboratory (Washington Hospital Center, Washington, D.C.) performed the qualitative and quantitative analyses for each study. The similarity of baseline patient and lesion characteristics across the various studies further validates the uniformity of the studies (15–21).
The primary analysis consisted of comparison of parameters in the two cohorts stratified by age. Continuous variables (e.g., minimal luminal diameter) were compared using the Student ttest, and categorical data were compared using the chi-square test (or the Fisher’s exact test where appropriate). A two-sided p value of p < 0.05 was required for statistical significance. Survival estimates were computed using Kaplan-Meier methods and compared using log-rank tests. Stepwise multivariable analysis using logistic regression models was performed to identify independent predictors of each end point. Several different multivariable models for predictors of death and vascular complications were constructed. Models that had a better discriminatory ability (higher c-statistic) and calibration (higher p value for the Hosmer-Lemeshow χ2statistic) were used. Missing data were not imputed, and mortality rates were not different between patients with complete versus missing data for the covariates evaluated. All statistical analyses were performed using SAS for Windows (version 6.12, SAS Institute, Cary, North Carolina).
Baseline clinical and angiographic characteristics
Of the 6,186 patients undergoing stenting, there were 301 aged patients, which constituted 4.9% of the study population. Significant differences existed in the prevalence of many established risk factors for coronary artery disease (Table 1). Aged patients were more likely to present with unstable angina and to have multivessel disease.
Angiographically, the aged patients had slightly but significantly smaller reference vessel and lesion length, and they were more likely to have moderate to severely calcified target lesions (Table 2). Other angiographic characteristics including vessel treated and American College of Cardiology/American Heart Association (ACC/AHA) lesion class were not significantly different between the two age groups.
Procedural and angiographic results
In keeping with a higher prevalence of heavily calcified lesions, aged patients were more likely to have pretreatment with rotational atherectomy. Otherwise, procedural characteristics (Table 3)were similar with nearly identical balloon:artery ratios and maximum post-stent balloon inflation pressures. Significant dissections before stenting were less common in aged patients, and aged patients required significantly shorter total stent length per treated vessel. Overall, lesion success and procedure rates were similar between the two age groups.
In-hospital major clinical events
In-hospital mortality was significantly higher in the aged (Table 4). Peri-procedural non-QMI was nonsignificantly higher in the aged group. Aged patients also had a significantly higher incidence of vascular and bleeding complications.
The mean follow-up time was 282 ± 85 days (Table 5). The one-year mortality in the aged group was significantly higher than in the nonaged (Fig. 1; Kaplan-Meier estimate 7.5% vs. 1.6%, log-rank p = 0.0001). There was no significant difference in the incidence of recurrent MI, TLR or TVR.
Multivariable modeling for predictors of mortality
Older age was a significant independent predictor of one-year mortality, with a 5% increase in risk per decade of life (per decade, odds ratio [OR] 1.05; 95% confidence interval [CI] 1.03–1.07, Table 6). The other significant predictors of mortality included history of prior MI (OR 2.03; 95% CI 1.35–3.07), presence of diabetes (OR 1.97; 95% CI 1.29–3.02) and three-vessel disease (OR 1.62; 95% CI 1.25–2.10).
Multivariable modeling for predictors of vascular and bleeding complications
In-hospital repeat revascularization (OR 9.94; 95% CI 3.93–25.15), female gender (OR 3.49; 95% CI 2.31–5.27) and older age (OR 1.06 per decade; 95% CI 1.04–1.08) were independent predictors of the occurrence of vascular or bleeding complications (Table 7).
Elderly patients have traditionally been considered a high-risk population for PCIs with a higher incidence of procedural failure and complications compared to younger patients (2–14). Our study of 301 patients ≥80 years old represents the largest reported series of aged patients undergoing coronary artery stenting, and more notably in the era of new second-generation stents and routine high-pressure dilation. Aged patients in our study had >97% procedure success rate despite smaller reference vessel diameters and more prevalent calcification, albeit with a significantly higher incidence of both in-hospital and one-year mortality compared to the nonaged patients.
Procedural results and acute clinical outcomes
Although the lesion complexity by ACC/AHA classification was not significantly different in the aged patients, the reference vessel diameter was significantly smaller, and heavily calcified lesions were more frequent, accounting for the associated greater use of pre-stenting rotational atherectomy. Similar findings have been reported in prior studies (4,5). Despite these unfavorable characteristics, the lesion success rate was high. The frequency of procedure success (defined as lesion success in the absence of death, MI or emergent coronary artery bypass graft [CABG]) was also no different from nonaged patients and was somewhat higher than that reported by DeGregorio et al. (4)in their recent single-center study of 137 patients ≥75 years (90% vs. 93%, p = NS). This difference may reflect a healthier population enrolled in the representative clinical trials. Of note, dissections prior to stenting were slightly less frequent in aged patients, and this accounts in part for the significantly shorter stent lengths that were required.
Mortality and aged patients
The aged patients had a higher incidence of in-hospital mortality (1.33% vs. 0.10%, p = 0.001) compared to the nonaged patients, although this incidence was still lower than the 2.2% to 3.1% in-hospital mortality previously reported (2,4). Not surprisingly, age was an independent predictor of overall mortality at one year, with an increased risk of 5% per decade of life. This increase was driven primarily by the continued increased risk for death more than 30 days after the index procedure (Fig. 1). Aged patients had a higher frequency of multivessel coronary artery disease, and the worse prognosis is likely a reflection of the expected poorer outcomes of patients with more severe and diffuse disease. There are limited comparative data on the long-term mortality in aged patients undergoing stenting, but the available studies have shown similar results. Abizaid et al. (2)reported 4.8% one-year mortality after stenting in subjects >80 years old. Among 137 stented patients >75 years old, DeGregorio et al. (4)reported a procedural mortality rate of 2.2% and an overall 7.3% mortality rate through one year of follow-up.
Myocardial infarction and aged patients
An increased risk for peri-procedural MI has been associated with increased plaque burden and extent of coronary artery disease (22,23). Certainly, in this aged population with higher frequency of multivessel disease and smaller reference vessel size it is likely that overall plaque burden was also increased. Furthermore, greater use of rotational atherectomy in the aged patients places them at a higher risk for peri-procedural MI (24). Previous reports have suggested an incidence of 0.4% to 2.2% for postprocedural MI in older patients (2–4,6). In our study no significant difference was seen in the incidence of MI in the aged patients compared to the nonaged patients (9.63% vs. 7.56%, p = 0.18), although the overall higher incidence of peri-procedural MI in both age groups may be due to the greater use of rotational atherectomy as well as routine and complete ascertainment of cardiac enzyme data following PCIs.
Vascular complications and aged patients
Along with the change in stent designs and high-pressure dilation, there has been a dramatic change in antithrombotic regimens following stent implantation, as oral antiplatelet therapy with aspirin and thienopyridines has replaced more aggressive anticoagulation protocols. Although the overall incidence of vascular complications has decreased with improvement in antithrombotic protocols and improved sheath management, older patients and women continue to have a higher incidence (4,6,13,15). Aged patients in our study similarly had more frequent postprocedural vascular and bleeding complications. Plausible explanations include more aggressive anticoagulation of these patients with complex lesion morphology, different pharmacodynamic effects of heparin in the elderly, and increased risk for vascular injury due to underlying peripheral vascular disease (25).
Because the overall use of platelet GpIIb/IIIa inhibitors was limited in our study (7.6%), we cannot assess the effects of these agents in the aged cohort. Certainly, the EPISTENT (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial) study has recently shown a reduction in peri-procedural non-QMI and one-year mortality with use of abciximab combined with coronary stenting compared to stenting without abciximab and balloon angioplasty with abciximab (26,27). Bleeding was not increased with use of abciximab in that study, but given the increased serious bleeding complications in aged patients in our study predominantly not receiving GpIIb/IIIa inhibitors, use of these agents in aged patients will require careful consideration of the benefits and risks.
Restenosis and aged patients
The aged patients in our study had a favorable long-term clinical restenosis outcome with no difference in TLR compared with nonaged patients during one-year follow-up (8.30% vs. 10.90%); the rates of TVR were nearly identical. This is in contrast with higher TLR rates in the consecutive series of older patients reported by DiGregorio et al. (4)(28% vs. 19%, p = 0.02), but similar to the 11% versus 14% to 15% TLR rates reported by Abizaid et al. (2). This probably reflects the aggressive initial results obtained rather than a physiologic difference in the restenosis process in the different age populations. The reduced risk for restenosis associated with the shorter lesion and stent lengths in the aged patients might have also balanced other potential increased risks for restenosis (28,29).
There are several limitations of this study. First, the data are pooled from several randomized trials. Because randomization by age is not possible and the number of aged patients undergoing revascularization procedures is still small, pooled analysis from similar trials was the only practical way to assess events in this group. Second, the outcome results may not be generalizable to the wider “real-world” population of aged patients undergoing stenting procedures; it is likely that “healthier” aged patients were enrolled in the clinical trials pooled for this analysis.
This analysis of 301 aged patients from a pooled data set of over 6,000 patients treated with stents demonstrates that stenting can be performed safely in this high-risk group with excellent acute results and low rates of clinical restenosis, albeit with a higher incidence of in-hospital and long-term mortality and with vascular and bleeding complications. Further studies will confirm whether more aggressive risk factor modification combined with selected use of coronary stenting will improve the long-term cardiac mortality in the aged population. Although the incidence of bleeding complications was lower than previously reported, efforts such as less anticoagulation, selective use of antiplatelet regimens (especially GpIIb/IIIa agents) and use of smaller-sized sheaths should be evaluated as measures to further reduce these risks in older patients.
☆ The original clinical studies were supported by contracts from Cordis/Johnson and Johnson Interventional Systems, Guidant/ACS, Boston Scientific/Medinol, and Medtronics/AVE. No outside financial support was provided for performing the analyses in this report.
- coronary artery bypass graft
- Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial
- myocardial infarction
- percutaneous coronary intervention
- quantitative coronary angiography
- Q-wave myocardial infarction
- Stent Antithrombotic Regimen Study
- target lesion revascularization
- target vessel revascularization
- Received April 12, 2000.
- Revision received October 16, 2000.
- Accepted November 17, 2000.
- American College of Cardiology
- ↵U.S. Bureau of the Census. Current Population Reports, Special Studies, P23–190, 65+ in the United States. Available via the Internet (http://www.census.gov). Accessed 6 Sept 1999.
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