Patient-Centered Cardiac Care for the Elderly: Title and subTitle BreakTIME for Reflection

The pace of scientific discovery and medical care delivery accelerates with each passing year. Physicians faced with an overwhelming number of publications strive to rapidly extract a study's "bottom line" (ie, how can these findings be distilled into simple heuristics, or rules of thumb, for patient care). While such a reductionist approach is understandable, some areas of medicine defy such simplification. The 1-year results of the Trial of Invasive versus Medical therapy in Elderly patients (TIME) study, published in this issue of THE JOURNAL,¹ clearly exemplify this situation.

The TIME study addresses the benefit of routine invasive management (cardiac catheterization and revascularization) in elderly patients with symptomatic coronary artery disease. Many physicians are facing this vexing clinical issue with increasing frequency. Patients aged 75 years or older represent a third of those hospitalized with acute ischemic events and account for more than half of all cardiac deaths.^{2 - 3} Demographic changes in the US population, later disease onset, and longer life expectancy for patients with heart disease have combined to expand the practice of "geriatric cardiology" substantially.

How should the findings from the TIME study be used to modify care algorithms for elderly patients with coronary disease? Prior to TIME, the vast majority of revascularization trials excluded patients older than 75 years.⁴ The success of TIME in enrolling elderly patients (ie, mean age, 80 years) should encourage future trials to be more inclusive of elderly patients. The study also addressed the "upstream" decision of whether to perform catheterization rather than centering solely on the use of revascularization once angiographic information is known. By such a design, the TIME investigators included a more representative patient population and more closely modeled the key decision point for elderly patients. The TIME investigators also assessed quality of life issues (symptoms, need for medications, functional status) in addition to discrete clinical events (death, recurrent myocardial infarction, rehospitalization) in the primary efficacy assessment.

Perhaps most important, the TIME study provided longitudinal data on treatment outcomes. These downstream results provide for a richer, albeit more complex, perspective. The initial TIME results demonstrated that invasive management significantly improved functional outcomes and was also associated with a higher mortality trend (8.5% vs 4.1%, P = .15) at 6 months.⁵ However, these trends reversed between 6 months and 1 year with conservatively treated patients having greater gains in functional outcomes and slightly higher mortality rates. As a result, the only significant treatment difference at 1 year was a reduced need for rehospitalization and revascularization among patients in the invasive therapy group.

Interpretation of these findings may well be influenced by a clinician's preexisting beliefs. Physicians who generally favor a conservative approach will point out that the up-front risks of an invasive strategy do not appear to be counterbalanced long-term by either quantity or quality of life gains. Differences in late revascularization would likewise be discounted as primarily being driven more by physician preferences than by actual patient need. Proponents of conservative care would therefore conclude that this trial supports a "watch and wait" approach as the preferred strategy in elderly patients with coronary disease.

In contrast, physicians who favor an invasive strategy would point to the 50% of medically treated patients who required follow-up intervention as "treatment failures." They might also view these treatment crossovers as the explanation for the narrowing of the functional status outcomes over time between the 2 treatment groups. Furthermore, an upfront invasive strategy may be viewed as safer by eliminating the later downstream risk for intervention in urgent or emergent conditions.

Regardless of perspectives regarding the overall conclusions, application of these findings to the individual elderly patient is even more challenging. For example, information regarding how patients enrolled in this trial compared with those who were screened is limited; however, the 1-year mortality rate (<10%) appears low relative to a 40% death rate observed in an unselected, similarly aged patient population with myocardial infarction.⁶ Similarly, the overall revascularization group mortality rate for TIME was reported at 2.5%, again 2- to 4-fold lower than observed in community-based octogenarian cohorts undergoing angioplasty or coronary artery bypass surgery.⁷

The limited size of the study raises other challenges. Although there was no significant difference in 1-year mortality, the hazard ratio was 1.51 (95% confidence interval, 0.72-3.16) favoring conservative treatment. This indicates that the invasive strategy may have reduced mortality by as much as 28% or increased it by more than 3 times relative to conservative care. The study's size also resulted in limited ability to examine whether the treatment effect varied among important patient subgroups. For example, in the Coronary Artery Surgery Study (CASS)⁸ and other revascularization trials,⁹ the benefits of treatment tended to be proportional to the patient's angina class, coronary disease severity, ventricular function, or presence of diabetes. These findings make it unlikely that a single global treatment recommendation will hold for all elderly patients with coronary disease.

Longer-term follow-up is needed to complete the treatment comparisons. For instance, it is unknown whether the 3- to 5-year treatment survival curves in the TIME study will cross, as was seen in CASS. Moreover, it is interesting to consider how the study results may have differed depending on the treatment mode, such as whether acute quality of life gains would have been more "durable" had coronary artery bypass surgery been the primary mode of revascularization. Answers to other questions, such as how drug-eluting stents might have altered these findings or whether "optimized medical therapy" was truly optimal (ie, including aggressive lipid-lowering) require future larger invasive trials in this important patient population.

Until these trials are designed and completed, what should TIME's "bottom-line" be for the physician in deciding on a treatment strategy for the symptomatic elderly patient with angina? One message may simply be a confirmation that decisions regarding intervention in the elderly involve complex trade-offs. Current options mandate compromise as none provide win-win-win results of low treatment risk, longer survival, and improved quality of life. Rather than following simple algorithms, the decision process in the elderly patient must be individualized to reflect the patient's preferences.

Physicians can assist in the decision making process by providing patients with individualized prognostic information. Published models exist for estimating revascularization risks based on multiple clinical factors beyond chronological age alone.^{6 ,10} Other studies are beginning to identify risk factors for cognitive decline or physical disability following revascularization.^{11 - 13} Although more studies are needed, these risk stratification tools can provide more personalized estimates to patients' "what are my chances" question.

Comparison of long-term benefits gained from competing strategies remains difficult to assess and awaits future larger clinical trials and longer follow-up. In the interim, well-performed large observational cohort studies of elderly cardiac patients have begun to provide important clues for the effectiveness of revascularization in specific elderly subpopulations.¹⁴ Physicians also need to avoid imposing paternalistic values on care decisions of their elderly patients.¹⁵ Although some elderly patients may prefer less intervention, others are willing to accept more risk to improve their quantity or quality of life.¹⁶

The TIME study has provided important results that whet physicians' appetites for more, yet are simultaneously humbling. This study has demonstrated that elderly-specific trials are possible and can enrich current understanding of treatment of elderly patients with coronary heart disease. But, it has challenged physicians to find the TIME to convey patient-centered and evidence-based care approach for elderly patients.