Author + information
- Received September 14, 1999
- Revision received March 1, 2000
- Accepted April 13, 2000
- Published online September 1, 2000.
- Wayne B Batchelor, MD, MHSa,1,*,
- Kevin J Anstrom, MS∗,
- Lawrence H Muhlbaier, PhD∗,
- Ralph Grosswald, MPH†,
- William S Weintraub, MD, FACC§,
- William W O’Neill, MD, FACC‡,
- Eric D Peterson, MD, MPH, FACC∗,
- for the National Cardiovascular Network Collaboration
- ↵*Reprint requests and correspondence: Dr. Wayne B. Batchelor, Terrence Donnelly Heart Center, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada
We sought to define the risks facing octogenarians undergoing contemporary percutaneous coronary interventions (PCIs).
The procedural risks of PCI for octogenarians have not been well established.
We compared the clinical characteristics and in-hospital outcomes of 7,472 octogenarians (mean age 83 years) with those of 102,236 younger patients (mean age 62 years) who underwent PCI at 22 National Cardiovascular Network (NCN) hospitals from 1994 through 1997.
Octogenarians had more comorbidities, more extensive coronary disease and a two- to fourfold increased risk of complications, including death (3.8% vs. 1.1%), Q wave myocardial infarction (1.9% vs. 1.3%), stroke (0.58% vs. 0.23%), renal failure (3.2% vs. 1.0%) and vascular complications (6.7% vs. 3.3%) (p < 0.001 for all comparisons). Independent predictors of procedural mortality in octogenarians included shock (odds ratio [OR] 5.4, 95% confidence interval [CI] 3.3 to 8.8), acute myocardial infarction (OR 3.2, 95% CI 2.3 to 4.4), left ventricular ejection fraction (LVEF) <35% (OR 2.9, 95% CI 2.1 to 3.9), renal insufficiency (OR 2.8, 95% CI 2.0 to 3.8), first PCI (OR 2.3, 95% CI 1.7 to 3.3), age >85 years (OR 2.1, 95% CI 1.5 to 2.7) and diabetes mellitus (OR 1.5, 95% CI 1.1 to 2.0). For elective procedures, octogenarian mortality varied nearly 10-fold, and was strongly influenced by comorbidities (0.79% mortality with no risk factors vs. 7.2% with renal insufficiency or LVEF <35%). Despite similar case-mix, PCI outcomes in octogenarians improved significantly over the four years of observation (OR of 0.61 for death/myocardial infarction/stroke in 1997 vs. 1994; 95% CI 0.45 to 0.85).
Risks to octogenarians undergoing PCI are two- to fourfold higher than those of younger patients, strongly influenced by comorbidities, and have decreased in the stent era.
Octogenarians (age ≥80 years) comprise the fastest growing segment of the U.S. population (1,2). The high prevalence of coronary disease in this age group (3–5), combined with the dramatic growth of percutaneous coronary interventions (PCIs) have resulted in more frequent use of these procedures in the very elderly (6,7). Despite these trends, there are limited outcomes data on the efficacy and safety of contemporary PCIs in octogenarians. Randomized clinical trials in interventional cardiology have enrolled very few patients of this age, and observational studies have been hampered by small sample sizes (7–22), giving rise to wide confidence intervals on outcome variable estimates. Furthermore, patient case-mix has varied substantially between these studies, and all but one report (22) predated coronary stenting. As a result, PCI outcomes in octogenarians have varied widely in the published data (mortality from 0% to 19%) (Table 1), and the contemporary risks in this age group remain undefined.
Using the National Cardiovascular Network database (NCN), we compared the outcomes of octogenarians undergoing PCI with those of younger patients (<80 years old). The multicenter nature of this data base afforded an adequate sample size to study mortality and provided the opportunity to sample outcomes across a large number of interventional practices in the U.S. We also defined the independent predictors of mortality for octogenarians and the trends in their outcomes over the four-year period of observation (1994 through 1997).
NCN data base
The NCN is a multicenter collaboration established in 1994 to foster global cardiovascular interventional care contracts with large health care purchasers. Membership in NCN provides each institution with information on patient case-mix, practice patterns, resource utilization and procedure outcomes. Site-specific data are reported in a blinded and confidential manner, thereby promoting institutions to collect outcome data in an unbiased manner. To become an NCN member, institutions were required to meet a minimal annual procedure volume benchmark of 300 PCIs. The NCN hospitals voluntarily provided a central data coordinating center (Duke University, Durham, North Carolina) with routine data transfers on all consecutive interventional procedures performed at their centers during the study period. A list of the 22 NCN centers providing outcomes data for this study can be found in Appendix A.
Definition of variables
All demographic, clinical and angiographic data variables were defined, a priori, by the NCN Data Standards Committee. Procedure priority was defined as urgent if the index PCI was required within 24 h of presentation due to either unstable angina refractory to nitroglycerin or ongoing myocardial ischemia. All other procedures were considered elective. In-hospital mortality was defined as the occurrence of death during the postprocedural hospital phase. Myocardial infarction (MI) was defined as the development of new Q waves in two or more contiguous leads on a 12-lead electrocardiogram taken in the hospital up to 30 days after PCI. Cerebrovascular accident (CVA) was defined as a permanent loss of neurologic function (including coma) caused by an ischemic vascular event. Procedural success was defined as percent stenosis reduction of at least 20% in all coronary stenoses intervened upon, to <50% residual diameter stenosis (i.e., angiographic success), without the occurrence of death, MI or CVA after the procedure. Repeat revascularization was defined as the requirement for either emergency coronary artery bypass graft surgery (CABG) or urgent repeat PCI after the index intervention. Cardiogenic shock was defined as maximal systolic pressure <90 mm Hg for at least 30 min, unless treated with inotropes or intra-aortic balloon pump insertion, or pump failure as manifested by a cardiac index <2.2 liter/min per m2 and pulmonary capillary wedge pressure >18 mm Hg. Persistence of hypotension or pump failure after correction of contributing extramyocardial factors (e.g., hypovolemia, hypoxemia, acidosis) and/or peripheral signs of hypoperfusion (e.g., peripheral vasoconstriction, urine output <30 ml/h or altered sensorium) were also required. Postprocedure renal failure was defined as oliguria (urine output <30 ml/h) or anuria associated with a daily increase in serum creatinine and blood urea nitrogen of >1 mg/dl and >10 mg/dl, respectively, or the need for either hemodialysis or peritoneal dialysis at any time after the coronary intervention. Vascular complications included any one of the following: entry-site vessel occlusion, large groin hematoma prolonging the hospital stay, documented pseudoaneurysm formation, entry-site bleeding requiring transfusion or surgical repair, dissection of the aorta, iliac or femoral arteries or acute limb ischemia. Major blood loss was defined as that requiring transfusion of blood products after the procedure.
Coronary angiography was interpreted visually on site by each operator. Left main coronary artery disease was defined as ≥50% stenosis in the left main coronary artery. Stenoses ≥70% were considered significant in all other coronary arteries. Proximal left anterior descending coronary artery (LAD) disease was defined as significant coronary stenosis in the LAD proximal to the first septal perforator branch. Percutaneous coronary revascularization procedures were performed using conventional methods according to local practice and operator discretion.
Clinical characteristics and in-hospital outcomes were compared between the octogenarian cohort and patients <80 years old. In-hospital mortality was the primary end-point evaluated; however, the duration of the hospital stay (total and postprocedure lengths of hospital phase) and the rates of procedural success, MI, CVA, the composite of death/MI/CVA, renal failure, vascular complications and urgent revascularization were also compared. Variables were reported as the mean value ± SD for continuous variables or as percentages for dichotomous variables. Comparisons between octogenarians and the younger cohort were made using the chi-square test for categoric variables and the t test for continuous variables.
Multivariable logistic regression analysis was used to determine the baseline clinical and angiographic variables independently associated with procedural mortality within the octogenarian cohort. Variables were entered into the model on the basis of a univariate association with procedural mortality (p < 0.05), their clinical relevance, or both. Continuous variables were examined for a linear fit within the logistic regression models and were dichotomized when the linearity assumption was not supported. All variables in the final model were examined for pairwise interactions. The model was internally validated using a bootstrap method (23,24). For each of 100 bootstrap samples (samples of the same size as the original study group but with patients drawn randomly, with replacement, from the full study group), the model was refit to estimate the degree to which the predictive accuracy of the model would be expected to deteriorate when applied to an independent sample of patients (24). The final multivariable model was used to 1) quantify the short-term mortality risk for an octogenarian patient according to baseline clinical and angiographic characteristics that are readily available at the time of the procedure; 2) adjust the trends in outcome over time for any imbalances in baseline risk; and 3) provide the basis for a risk stratification scheme (25).
To examine trends in octogenarian outcomes over time, we compared the risk-adjusted outcomes (rates of procedural success, death, death/MI/CVA and vascular complications) in each of the last three years of the study (1995, 1996 and 1997) with outcomes from the first year of the study (1994). These comparisons were graphically displayed using odds ratio (OR) plots. Chi-square statistics were used to test for differences in event rates over the four years of the study. All statistical computations were performed using SAS software (SAS Institute, Inc., Cary, North Carolina).
Clinical and angiographic characteristics
The baseline clinical characteristics of the 7,472 octogenarians and the 102,236 younger patients are presented in Table 2. The mean ages of the two groups were 83 and 62 years, respectively. Octogenarians were more likely to be women and Caucasian and to have their intervention performed for urgent indications. Octogenarians were also more likely to have other comorbid illnesses and indexes of severe coronary disease (e.g., peripheral vascular disease, renal insufficiency, cerebrovascular disease, congestive heart failure, previous CABG and Canadian Cardiovascular Society class III or IV angina), but were less likely to have diabetes mellitus or to have had a previous PCI.
Baseline angiographic data are compared in Table 3. Left ventricular systolic function was well preserved in both cohorts, although the left ventricular ejection fraction (LVEF) was slightly lower in octogenarians (mean LVEF 47% vs. 49%). Left main coronary artery disease was uncommon in both groups. Octogenarians were more likely to have disease of the proximal LAD and multivessel disease (two- vs. three-vessel disease in 57% vs. 45%, respectively). A similar proportion of each cohort had interventions performed using stand-alone balloon angioplasty (∼50% of procedures) and coronary stenting (∼40% of procedures). Octogenarians were more likely to have a Rotablator procedure and less likely to have directional coronary atherectomy (DCA). Laser angioplasty and other devices were used with rarity (<1%) in both cohorts.
The overall mortality for the entire NCN study sample was 1.1%. Mortality demonstrated a curvilinear relation with age, ranging from ∼0.5% for patients <55 years old to nearly 5% for patients >85 years old (Fig. 1). The clinical outcomes of octogenarians compared with those of the younger cohort are presented in Table 4. Octogenarian mortality was relatively low, albeit more than threefold that of the younger cohort (3.8% vs. 1.1%; OR 3.6, 95% confidence interval [CI] 3.2 to 4.1). Procedural success was achieved in the majority of interventions, although slightly less commonly in the octogenarian cohort (84% vs. 89%, p < 0.001). Other in-hospital complications occurred 1.5 to 3.5 times more frequently in octogenarians, including the composite outcome of death/MI/CVA (4.9% vs. 1.9%), Q wave MI (1.9% vs. 1.3%), CVA (0.58% vs. 0.23%), renal failure (3.2% vs. 1.0%), major blood loss (9.9% vs. 3.6%) and vascular complications (6.7% vs. 3.3%). In-hospital repeat revascularization was performed after <5% of interventions in both age groups. The total duration of the hospital stay was on average 1.4 days longer for octogenarians, and the mean duration of the hospital stay after the procedure was approximately one day longer.
Predictors of mortality in octogenarians
Multivariable logistic regression analysis (Table 5)revealed the following independent predictors of in-hospital death for octogenarians (in rank order of importance, using ORs): cardiogenic shock, acute MI without shock, LVEF <35%, renal insufficiency, first PCI, age >85 years and diabetes mellitus. The C index for the final model was 0.75, and the mean C index for the bootstrap validation samples was also 0.75 (interquartile range 0.74 to 0.76), indicating internal validity of the model’s predictive ability within our study sample.
We examined mortality after stratifying octogenarians into risk groups created from the predictor variables identified by our regression model. Patients were grouped into a single risk category by considering the presence or absence of each independent mortality predictor sequentially, in order of importance. Figure 2 displays the observed mortality within each of these groups, along with corresponding 95% CIs. Octogenarian mortality varied widely, from <1% to 31%, depending on coexisting risk factors. The vast majority of procedures were performed electively (no shock or acute MI). Within this group, mortality was low (2.2%) but varied nearly 10-fold, from 0.79% (no risk factors) to 7.2% (renal insufficiency or impaired LVEF).
Trends in case-mix, device use and octogenarian outcomes over time
The clinical case-mix of NCN patients, including octogenarians, remained relatively constant over the four study years. For example, the mean age, proportion of women and prevalence of risk factors (diabetes, renal disease, LVEF <35% and age ≥85 years), as well as severity of coronary disease, were comparable for octogenarians across all years. Given the constancy of patient characteristics over time, the predicted mortality risk for octogenarians did not vary substantially over the four years. However, the interventional techniques performed in octogenarians did change substantially over time. The rate of coronary stent use increased from only 4% in the first quarter of 1994 to over 66% in the last quarter of 1997. Over this time frame, there was a corresponding decrease in atheroablative procedures (DCA or Rotablator), from 18% to 5%.
In general, procedural outcomes in all patients improved progressively over the time course of the study. However, octogenarians showed a greater improvement in outcomes over the four years of study than did younger patients (Table 6). Figure 3 illustrates the risk-adjusted likelihood of procedural success, death, death/MI/CVA and vascular complications for octogenarians undergoing PCI during each of the last three years (1995, 1996 and 1997) compared with the first year (1994). There was a general trend toward improved outcomes over time, such that by 1997 the likelihood of procedural success had significantly increased (OR 1.5, 95% CI 1.2 to 1.9) and the risk of death/MI/CVA (OR 0.61, 95% CI 0.45 to 0.85) and vascular complications (OR 0.64, 95% CI 0.45 to 0.93) had significantly decreased, compared with 1994. The reduction in mortality between 1994 and 1997 also approached statistical significance (OR 0.71, 95% CI 0.49 to 1.03).
This study represents the largest procedural outcomes study in octogenarians undergoing PCI in the era of intracoronary stenting. We report that, with appropriate case selection, these interventions can be performed with high rates of procedural success and acceptably low mortality (3.8%) and morbidity. However, the risks remain approximately two- to fourfold higher in the very elderly as compared with younger patients. For elective procedures, procedural risks vary widely for octogenarians and are strongly influenced by comorbidities such as left ventricular impairment, renal insufficiency, diabetes mellitus and extreme age (age ≥85 years). The progressively higher procedural success rates, associated with a 37% reduction in major cardiovascular events (death/MI/stroke) over the four years of the study, suggest that PCI outcomes in the very elderly have improved over time. As these improved outcomes were not attributable to shifts in case-mix and baseline risk, they are more likely attributable to advances in interventional technique, operator skill or adjunctive medical therapy.
Comparisons with previous studies
As a part of the aging process, coronary arteries are prone to dilation, tortuosity, medial calcification and impairment of endothelial function (26–29). These pathophysiologic alterations, in addition to a higher prevalence of other cardiac and extracardiac comorbidities, have contributed to the lower success rates and higher mortality reported for octogenarians undergoing catheter-based coronary interventions (7–22). However, the procedural mortality reported in our study is favorable as compared with previous studies (Table 1). Most previous reports have emerged from single academic institutional experiences with small sample sizes (8,10–12), and all but one (22) predated the use of intracoronary stenting, now recognized as an effective technique in interventional cardiology (30,31). The only other large-scale observational study reported on the U.S. National Medicare experience between 1987 to 1990, therefore also predating the use of intracoronary stents (7). Of 225,915 Medicare patients undergoing PCIs during this time frame, 8.5% (∼19,000) were octogenarians, and their 30-day mortality rate was high (8%). Given the more contemporary time frame of our study, as well as representation across a broad spectrum of both community and academic interventional practices, we feel that the short-term outcomes presented in our study are more reflective of current interventional practices in the United States at experienced institutions. In agreement with our findings, the French Registry (22) recently reported a similarly favorable short-term procedural mortality rate (3.4%) for patients ≥75 years old undergoing coronary stenting.
Predictors of risk in octogenarians
Our study had an adequate sample size to examine the independent predictors of mortality for octogenarians undergoing coronary interventions. As expected, indicators of clinical stability such as cardiogenic shock and acute MI were the strongest determinants of mortality. The seven predictor variables defined from our multivariable model (shock, acute MI, left ventricular systolic function, renal insufficiency, first coronary angioplasty, increased age and diabetes mellitus) bear some similarity to those emerging from models previously developed from younger patients (32–34). The observation that octogenarians who had a previous PCI faced less risk than those undergoing their first procedure was interesting, but could simply be due to the fact that survival from a first procedure is requisite to having a second. Alternatively, it is possible that the pathophysiology of restenosis lesions (intimal hyperplasia) may present a more stable plaque that is more amenable to balloon dilation than is de novo atherosclerotic plaque.
Age, itself, was also an important independent outcome predictor among octogenarians. “Older” octogenarians (age ≥85 years) faced a twofold risk compared with “younger” octogenarians (age <85 years). In the development of our risk model, we chose to represent age as a dichotomous variable (<85 or ≥85 years), because the increase in risk was most dramatic beyond age 85 years, and expressing age as a continuous variable (even using higher order terms such as age2 or age3) did not add significant predictive power to the multivariable model, as compared with the use of the dichotomous variable. Still, it must be recognized that the procedural risk in octogenarians increases in a continuous, curvilinear manner with increasing age.
An important insight from the predictive model was the heterogeneity of risk observed for octogenarians. Risks were relatively low under elective conditions (i.e., no shock or acute MI) and in the absence of renal insufficiency or impaired left ventricular systolic function. Indeed, it was the selection of these “low risk” octogenarians that contributed to the favorable octogenarian outcomes observed in this study. If validated in other octogenarian cohorts, consideration of the seven independent prognostic variables garnered from our model may prove useful in quantifying risk and therefore assessing risk–benefit relationships in elderly patients undergoing catheter-based coronary interventions in the future.
Trends in octogenarian outcomes over time
Over the four years of this study, procedural success rates for the entire NCN cohort improved, and major procedural cardiovascular complications slightly decreased. Interestingly, the greatest risk reduction over time was observed in octogenarians, where the risk of death and major cardiovascular complications decreased by 29% and 37%, respectively. In contrast, younger patients showed little change in what began as a very low risk of mortality or major cardiovascular complications over time. The favorable outcome trends observed in octogenarians did not appear to be attributable to changes in case-mix over time, because the clinical characteristics, risk factors and predicted mortality of octogenarians remained relatively constant throughout the study period (predicted mortality risk was 3.8% for both 1994 and 1997 in octogenarians). This phenomenon of improving interventional outcomes in the elderly over time is consistent with trends noted in the past decade (7,21) and may have been a result of advances in interventional technique, increasing operator experience or improved adjunctive medical therapy (i.e., safe and more efficacious antiplatelet therapies that replaced anticoagulation regimens during this time). The dramatic increase in the use of intracoronary stents in octogenarians during the four years of evaluation (from only 6% in 1994 to >66% in 1997) suggests that this technical advance may have been a major contributor to the improved outcomes experienced during this period.
When assessing risk, it is possible that a patient’s chronologic age, per se, may be less important than the patient’s general physical condition (physiologic age). Because case selection was left to the discretion of the operator, there may have been a selection bias in favor of the lowest risk octogenarians (i.e., those with the most favorable physiologic age). However, octogenarians in this study were more symptomatic (84% had Canadian Cardiovascular Society class III/IV angina), had more extensive coronary artery disease (57% had multivessel disease) and carried a substantially greater burden of comorbidities than did younger patients. This suggests that the elderly were truly a higher risk cohort. Lesion characteristics (e.g., vessel size, tortuosity, thrombus, calcification, lesion length) and periprocedural adjunctive medical therapy (e.g., glycoprotein IIb/IIIa platelet receptor inhibitor use or systemic anticoagulation) were not recorded in this data base. Furthermore, postprocedure cardiac enzymes were not systematically collected, so that only Q wave MI could be assessed as an endpoint.
This study does not directly address whether elderly patients with multivessel disease should undergo CABG or PCI. However, given the longer duration of the hospital stay (>7 days) and high mortality (8%) and stroke rates (10%) observed among octogenarians undergoing CABG in the same NCN cohort (35), PCI may be a reasonable initial revascularization strategy for octogenarians suitable for either procedure. Without direct comparative data, revascularization approaches must continue to be made on an individual basis.
Like several other large national cardiovascular registries, the NCN data base was not externally validated. However, all institutions agreed to strict adherence to the specific variable definitions that were defined a priori. Furthermore, institution-specific outcomes were not released outside each institution, thereby encouraging honest reporting of outcomes. Finally, it should be emphasized that the results of this study are only generalizable to selected octogenarians undergoing PCI in high volume centers with experienced operators such as those participating in the NCN collaboration.
The risks to octogenarians undergoing contemporary PCI are two- to fourfold higher than those of younger patients, strongly influenced by comorbidities, and appear to have declined during the era of coronary stenting. The results of this report, as well as other studies that provide insights into long-term outcomes, quality of life and cost-effectiveness of coronary revascularization strategies, are requisite to a more complete understanding of the risk–benefit trade-off of these invasive interventions in this rapidly growing segment of our population.
Participating centers in the national cardiovascular network data base
Duke University Medical Center, Durham, North Carolina; Bryan Memorial Hospital, Lincoln, Nebraska; Albany Medical Center Hospital, Albany, New York; Christ Hospital, Cincinnati, Ohio; Hillcrest Medical Center, Tulsa, Oklahoma; Shadyside Hospital, Pittsburgh, Pennsylvania; St. John’s Hospital, Springfield, Illinois; William Beaumont Hospital, Royal Oak, Michigan; Abbott-Northwestern Hospital, Minneapolis, Minnesota; St. Vincent’s Infirmary, Little Rock, Arkansas; Mid America Heart Institute, Kansas City, Missouri; Mercy Heart Institute, Sacramento, California; Washington Hospital Center, Washington, District of Columbia; St. Luke’s Medical Center, Milwaukee, Wisconsin; Emory Heart Center, Atlanta, Georgia; Lenox Hill Hospital, New York, New York; Indiana Heart Institute, Indianapolis, Indiana; Jewish Hospital Heart and Lung Institute, Louisville, Kentucky; Maine Medical Center, Portland, Maine; Florida Hospital, Orlando, Florida; St. Thomas Hospital, Nashville, Tennessee; Baylor University Hospital, Houston, Texas.
↵1 Dr. Batchelor is a Research Fellow at the Heart and Stroke Foundation of Canada.
☆ Dr. Peterson is supported by the American Federation for Aging Research as a 1998 Paul Beeson Faculty Scholar. The National Cardiovascular Network provided financial support to the Duke University Clinical Research Institute as the coordinating center.
- coronary artery bypass graft surgery
- confidence interval
- cerebrovascular accident
- directional coronary atherectomy
- left anterior descending coronary artery
- left ventricular ejection fraction
- myocardial infarction
- National Cardiovascular Network
- odds ratio
- percutaneous coronary intervention
- Received September 14, 1999.
- Revision received March 1, 2000.
- Accepted April 13, 2000.
- American College of Cardiology
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