|Home | About | Journals | Submit | Contact Us | Français|
This is Part II of a two-part article on treatment of acute coronary syndrome in the older population. Part I (published in the October issue of Clinical Geriatrics) analyzed the differential utilization of invasive therapies with respect to age and heart disease. Part II summarizes information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.
The elderly are at high risk of acute coronary syndromes (ACS), but receive less cardiac medication and invasive care than other age groups.1 Two factors may explain this practice: (1) limited data from randomized clinical trials and (2) uncertainty about benefit and risk with advanced age.2
A basic understanding of how competing treatment strategies for ACS influence outcomes in older persons remains elusive. Part I of this review3 analyzed the differential utilization of therapies, challenges in diagnosing ACS in the context of comorbid conditions, and the lethality of ACS in older adults. The goal of Part II is to summarize published ACS outcomes results from invasive treatment strategies (percutaneous coronary interventions [PCIs] or coronary artery bypass grafting [CABG]) in older persons. Through this analysis, we hope to provide an improved understanding of efficacy and appropriateness of ACS treatment (both medical and interventional) in the elderly.
An ongoing controversy over treatment for older adults presenting with ACS is defined by the therapeutic choice of an ischemia-guided strategy versus an early invasive strategy. An ischemia-guided strategy refers to an initial plan for medical therapy with catheterization for recurrent symptoms (or stress-induced ischemia), whereas an early invasive strategy dictates cardiac catheterization within 48 hours of ACS presentation. Although therapy should be tailored to the level of risk, several studies have established superiority of an early invasive strategy in a broad population of patients, including the elderly, with unstable angina and non-ST elevation myocardial infarction (NSTEMI).4–8
FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) was the first randomized comparison of a conservative versus invasive strategy to demonstrate a significant event rate reduction in favor of an invasive strategy in the overall population.9 The protocol incorporated a 4-day stabilization period before intervention; thus, it was a “delayed invasive” strategy. The 6-month rate of death or myocardial infarction (MI) was lower with the invasive arm versus the conservative arm (8.3% vs 10.3%; P = 0.03), and at 1 year the death rate was significantly reduced (2.2% vs 3.9%; P = 0.016).9 Although this study excluded patients 75 years of age and older, the subgroup 65 years of age and older had a greater absolute (5.3% vs 0%) and relative (33.5% vs 0%) reduction in death or MI at 6 months as compared with the younger subgroup. This benefit increased (Figure) at 2 years and again at 5 years.10 The positive influence of an invasive strategy in FRISC II may be explained by the high rate of revascularization (78% in the invasive arm) and concurrent medical therapy, optimizing the benefit of revascularization.
Using the Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis In Myocardial Infarction (TACTICS-TIMI 18) trial,8 Bach et al analyzed clinical outcome by age in older patients presenting with ACS who were randomly assigned to an early invasive or conservative management strategy. This multicenter trial involved 2220 patients with unstable angina and NSTEMI. At 6 months, the primary composite endpoint of death, MI, or rehospitalization was lower in the invasive arm than in the conservative arm (15.9% vs 19.4%; P = 0.026). An elderly age subgroup analysis from this trial11 found a substantial treatment effect in favor of an invasive strategy for the reduction of death or MI with advancing age. When the elderly were compared with younger patients, the early invasive strategy yielded a greater absolute (4.1% vs 1%) and relative (42% vs 20.4%) risk reduction in death or MI at 30 days in the subgroup 65 years of age and older. Similarly, among patients 75 years of age and older, the absolute (10.8%) and relative (56%) reduction in death or MI with the early invasive strategy was even greater (event rates: 10.8% vs 21.6%; P = 0.02). A significant age–treatment interaction was present in favor of better outcome with invasive care in those 75 years of age and older (P = 0.044). This benefit persisted despite a threefold higher risk of major bleeding with the early invasive strategy in patients 75 years of age and older (16.6% vs 6.5%; P = 0.009). From a clinical perspective, the number needed to treat with invasive care to prevent one death or MI was 250 among those age 65 years and younger, 21 among those age 66–74, and just nine for those 75 years of age and older ((Table). Consistent with the findings from FRISC II, younger patients (< 65 yr) had good outcomes regardless of the treatment strategy.
The analysis of the effect of age on outcomes in the TACTICS-TIMI 18 trial led to several conclusions challenging assumptions and current practice patterns in older persons. First, as compared with younger patients, older patients with unstable angina and NSTEMI have a markedly increased rate of adverse ischemic outcomes. Second, routine early invasive strategy reduces death or nonfatal MI among elderly patients. Third, this aggressive strategy has greater absolute benefit for reduction of death or nonfatal MI in older patients than in younger patients. Fourth, the early invasive strategy may be more cost-effective in the elderly, largely because it prevents death or MI in this group. Fifth, a routine early invasive strategy does not increase the incidence of stroke, even among older persons.
But the news isn’t all good for an early invasive strategy. A recent trial comparing selective invasive versus routine invasive care (Invasive versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]) in patients with positive troponins and NSTEMI demonstrated no overall differences with regard to the combined endpoint (death, MI, or rehospitalization for angina) at 1 year, with a trend to less angina and fewer fatal MIs among invasively managed patients.12 The average age was 62 years. However, in an elderly subgroup (≥ 65 yr) analysis, a nonsignificant trend favored early invasive care.12 Another study, an observational analysis in a community population, failed to demonstrate an early benefit from an invasive strategy with inhospital survival in the elderly subgroup (≥ 75 yr).13 These inconsistent observations highlight the need for continued caution in the uniform application of trial results in the elderly13 and underscore the need for further randomized controlled trials of older persons with regard to treatment strategies for ACS.
In the subgroup of patients with ACS identified as having ST elevation myocardial infarction (STEMI), the current rationale is to reperfuse ischemic myocardium emergently. The benefits are thought to outweigh the risk in the vast majority of patients in this higher-risk group. Reperfusion therapy is approached by two mechanisms emergently: (1) fibrinolysis or (2) coronary angiography with PCI.
Three small trials were performed to specifically address the question of fibrinolytic therapy or PCI in elderly STEMI patients. The first trial randomized patients over 75 years of age (n = 87) to PCI versus fibrinolytic therapy (streptokinase). Patients treated with PCI demonstrated lower rates of death, MI, or stroke at 30 days (9% vs 29%; P = 0.01).14 Another trial randomized patients 70 years of age and older (n = 130) to PCI (with stenting) versus fibrinolytic therapy (tPA). At 6 months, no difference in mortality rate was observed, but significantly fewer subsequent revascularization procedures in the PCI group (9% vs 61%; P = 0.001) occurred and the PCI group had a lower composite of death, MI, or revascularization (29% vs 93%; P = 0.001).15 A prospective randomized trial, Senior Primary Angioplasty in Myocardial Infarction (Senior PAMI), randomized patients 70 years of age and older (n = 481) presenting less than 12 hours from symptom onset to PCI versus fibrinolytic therapy.16 In this study, a nonsignificant 36% reduction in death or nonfatal stroke (11.3% PCI vs 13% thrombolytic therapy; P = 0.57) resulted. If recurrence of ischemia was added to the composite endpoint a significant 55% reduction in death, stroke, or reinfarction (11.6% PCI vs 18% thrombolytic therapy; P = 0.05) favored PCI. No difference between reperfusion strategies was seen in the small subgroup 80 years of age and older (n = 131).16
Although these trials represent small numbers, the advantages of PCI over fibrinolysis appear to be amplified when analyzing pooled trials to increase the number of older patients. The investigators expanded the analysis to include 22 randomized trials of PCI versus fibrinolytic therapy. There was a benefit with PCI, particularly if the patient arrived 2 hours after symptom onset or if the patient was 65 years of age or older.17 A subgroup analysis found that the absolute mortality advantage of PCI increased with age from 1% at 65 years to 6.9% at 85 years of age and older.18
The Angioplasty Compared to MEdical therapy (ACME) trial was the first randomized trial to examine the effect of different therapies on quality-of-life measures,19 showing a greater improvement in physical and psychological measures in patients assigned angioplasty. The larger second Randomized Intervention Treatment of Angina (RITA-2) trial20 confirmed these findings up to 1 year, particularly for physical functioning, vitality, and general health. An attenuation of this improvement over 3 years was partly attributed to 27% of medically-treated patients receiving revascularization during follow-up.19 In the present study, similar tools for quality-of-life assessment were applied to an elderly population and confirmed an overall improvement in general health and pain status with both medical and revascularization therapies.19 This effect was somewhat greater after revascularization in both patient groups, minimizing the difference between treatments in overall results. The improvements in symptomatic status and general well-being are particularly important in view of the fact that quality of life is of primary importance for 80-year-old patients—more important than prolongation of life.
The characteristics of patients undergoing heart surgery have changed over time. The patients undergoing operations for coronary artery disease (CAD) are now older with more comorbid conditions. Warner et al21 prospectively studied and compared 23,512 patients undergoing CABG during three time periods from 1981 to 1995. The mean age and the percentage of patients age 65 years or older were significantly higher in the later time periods. In a multivariate analysis for predictors of mortality, these researchers found that patients age 65 and older in the more recent cohort of patients had an odds ratio of 2.7 for mortality.21 Patients age 80 and over were found to have a significantly higher risk of any complication with surgery, including neurologic events, pneumonia, arrhythmias, or wound infection. Despite higher complication and mortality rates in older persons, the question that remains is whether the potential benefit of CABG (or PCI) outweighs the risk of the procedure.
Given similar health status benefits, the principal barrier in recommending CABG (instead of PCI) to older patients appears to be greater perceived risk. Yet, several studies have shown that age alone is insufficient to prohibit CABG surgery.22–25 Keon26 demonstrated a steady reduction in mortality from isolated CABG in the elderly over the past three decades. While he attributed these results to improved surgical techniques, better postoperative care, and careful selection of surgical candidates, his finding of a marginal increase in mortality among older patients (3.7% vs 1.6%) argues that age alone is a misleading criteria for avoidance of cardiac surgery.26 Using a prospective design, a consecutive series of 690 patients undergoing CABG had serial assessments of procedural impact on measures of functional status, symptom burden, and quality of life.27 Older patients demonstrated absolute improvements in physical function, angina frequency, and quality of life, and without statistically significant differences between older and younger subjects. In fact, the trends favored a greater reduction in angina frequency and an enhanced overall quality of life 1 year after surgery in the elderly as compared with younger subjects. Graham and colleagues28 found revascularization to be superior to optimal medical treatment: patients age 80 years and older undergoing CABG had a 4-year survival rate of 77.4% as compared with 60.3% in patients treated medically. In particular, these researchers noted improved 1-year survival in the subset of patients with left main CAD undergoing revascularization.
These findings, along with previous studies, indicate that older subjects confront increased risk of complications from heart disease than younger cohorts,29 suggesting that elderly patients may benefit more from interventions than younger counterparts.
The prevailing invasive treatment strategy for ACS in the elderly is PCI. This dominant strategy suggests that a “less-invasive” myocardial revascularization procedure (such as PCI) affords attenuated morbidity and mortality in older persons as compared to CABG.
In an early attempt to understand the influence of age on outcomes in patients with CAD, the Bypass Angioplasty Revascularization Investigation (BARI) trial prospectively enrolled 1829 patients with symptomatic multivessel CAD requiring revascularization who were randomly assigned to undergo either CABG or PCI.30 Of the patients, 709 (39%) were age 65 to 80 years at baseline; the other 1120 were younger than 65 years. The inhospital 30-day mortality rate for PCI and CABG in the younger patients was 0.7% and 1.1%, respectively, and the rate for patients age 65 years or older was 1.7% and 1.7%, respectively. In both age groups, CABG resulted in greater relief of angina and fewer repeat procedures. The 5-year survival rate in patients younger than age 65 years was 91.5% for CABG and 89.5% for PCI. In patients age 65 years or older, the 5-year survival rate was 85.7% for CABG and 81.4% for PCI. It appears within the context of the BARI trial that older patients assigned to CABG (instead of PCI) had less recurrent angina, were less likely to undergo repeat procedures, and were less likely to die.
In a European randomized controlled trial, 255 patients age 75 years or older were randomized to optimal medical treatment or revascularization (PCI or CABG).31 Patients in both groups were clinically improved with enhanced general well-being during follow-up, but this improvement was greater after surgical revascularization. A full third of patients in the optimum medical group crossed over to revascularization during follow-up for refractory symptoms. Overall, the invasive approach was followed by a significantly lower rate of major adverse cardiac events, particularly nonfatal ischemic events, and carried only a marginal intervention.
Upon review of the New York Cardiac Registry, Hannan et al32 compared outcomes of PCI (with drugeluting stents) versus CABG. The major findings of the study were that among patients with three-vessel disease or two-vessel disease, those treated with CABG had significantly lower adjusted rates of death and of death or MI than those treated with drug-eluting stents; and patients who were at least 80 years old who underwent CABG had significantly lower rates of death or MI.
Open-heart surgery in octogenarians has risen steadily since the 1980s. A number of factors justify this increase. Cane and colleagues33 demonstrated actuarial survival for octogenarians undergoing CABG that is comparable to that of the age-matched population. They concluded that octogenarians should be offered the opportunity for CABG “with the expectation of reasonable results and late survival that parallels their demographic group.” In a retrospective study of the Society of Thoracic Surgeons National Database, Bridges et al34 found that operative mortality and complication rates from CABG are highest for those in their 90s and over age 100. But with careful patient selection, the study found, most of the patients had a lower risk of CABG-related mortality.34 Other investigators have noted that octogenarians enjoy a higher quality of life after undergoing CABG or valve surgery. For example, in their review of 68 octogenarians undergoing CABG or valve surgery, Kumar and colleagues35 found that approximately 85% of patients reported that, in retrospect, they definitely would have made the decision to undergo open-heart surgery.
The coalescence of a rapidly expanding cohort of older persons and the dominance of heart disease as the major cause of mortality in the United States challenges healthcare providers to analyze therapeutic strategies for ACS in older patients. Age influences the presentation of disease and is entwined with comorbid conditions; therefore, age may bias treatment strategy selection toward less-invasive interventions such as PCI and away from more invasive strategies such as CABG.
Selection of older patients for an early invasive strategy is complex, given the need to consider risk from disease and risk from intervention, but given the benefits observed in recent trials, age alone should not preclude its consideration, but rather should intensify it.
We must explicitly ask which strategies are beneficial. This review suggests that “interventional” strategies provide an opportunity for improved outcomes in older persons with ACS. The choice of which intervention is better to use (PCI or CABG) remains undefined, but future studies must include older patients and define age-sensitive outcomes.
This manuscript was supported by NIH Grant 1R01AG025801-01A1.
This activity is sponsored by NACCME.
All those in a position to control content of continuing education programs sponsored by NACCME, LLC are required to disclose any relevant financial relationships with relevant commercial companies related to this activity. All relevant relationships that are identified are reviewed for potential conflicts of interest. If a conflict is identified, it is the responsibility of NACCME to initiate a mechanism to resolve the conflict(s). The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation. All educational materials are reviewed for fair balance, scientific objectivity of studies reported, and levels of evidence.
Planning Committee: T. Levy, NACCME, and C. Ciraulo and S. Gephart, HMP Communications, have disclosed no relevant financial relationship with any commercial interest.
Editor: M. Edwards has disclosed no relevant financial relationship with any commercial interest.
Dr. Sheridan has disclosed that he is a consultant for Pfizer.
Dr. Stearns, Dr. Massing, Dr. Stouffer, Ms. D’Arcy, and Dr. Carey have disclosed no relevant financial relationship with any commercial interest.
Clinical Reviewer: Dr. Christmas has disclosed no relevant financial relationship with any commercial interest.
Internists, family practitioners, geriatricians, cardiologists, and others who care for older patients.
METHOD OF PARTICIPATION/SUCCESSFUL COMPLETION
To be eligible for documentation of credit, participants must read all article content, log on to www.naccme.com to complete the online post-test with a score of 70% or better, and complete the online evaluation form. Participants who successfully complete the post-test and evaluation form online may immediately print their documentation of credit. Please e-mail moc.emccan@ofni or call (609) 371-1137 if you have questions or need additional information.
This activity is sponsored by the North American Center for Continuing Medical Education (NACCME). NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NACCME designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. This activity has been planned and produced in accordance with the ACCME Essential Areas and Policies.
Upon completion of this educational activity, participants should be able to: