Review

Percutaneous Coronary Intervention in the Elderly Patient (Part II of II)

Lloyd W. Klein, MD
Lloyd W. Klein, MD
Continued (Part II of II) Cardiogenic Shock Although several registries suggest that elderly patients who present with cardiogenic shock have a significant improvement in survival with PCI, neither the SHOCK trial nor the Northern New England Shock Study showed much benefit, and may have shown worse outcomes. These studies demonstrated 34% and 12% absolute differences, respectively in early mortality between elderly patients and younger patients with shock treated with PCI. Elderly patients with cardiogenic shock was one subject of the very complex SHOCK trial65 and registry.66 The SHOCK trial65 randomized 302 patients in cardiogenic shock to early revascularization therapy or to initial medical stabilization. There was significantly lower 6-month mortality in patients randomized to revascularization (PCI or surgical) than those treated medically, but this benefit was observed only in patients 75 years did not appear to benefit from a routine strategy of early revascularization. The 30-day survival of patients greater than or equal to 75 years was worse (20.8% vs. 34.4%) in those treated with emergency revascularization. Hochman67 did not believe these data were definitive, and suggested that baseline differences could have been the determining factor. The principal investigator of SHOCK identified the fact that there were only 56 patients 75 years of age or older enrolled in the SHOCK trial, and hence, a definitive conclusion in this subgroup was not possible. Additionally, the mortality rate for patients > 75 years of age who received initial medical stabilization was similar to younger patients, and was therefore unexpectedly low (53.1%), further qualifying the conclusion. Inequalities in baseline characteristics of the 56 elderly patients assigned to the emergency revascularization group compared to the medical therapy group may also have contributed to an apparent lack of treatment effect.67 Conversely, the SHOCK Registry, based on 277 elderly shock patients, did show a marked survival benefit favoring PCI in the elderly.66 Elderly patients clinically selected for emergency revascularization demonstrated improved survival when treated with emergent PCI. Interestingly, the mean age of randomized patients was lower than registry patients (65.8 vs. 68.5 years; p 67–69 In these registries, between 16% and 33% of elderly patients with shock were selected for emergency PCI. The Northern New England Cardiovascular Registry68 evaluated the results in cardiogenic shock patients over a 10-year experience in their prospective registry in Northern New England. The clinical characteristics and in hospital mortality for elderly patients > 75 years of age were compared to those 70 In patients without shock, the adjusted relative risk for long-term mortality was 4.4 in older versus younger patients (p p = 0.051). This finding suggests that certain elderly shock patients are highly salvageable. Among the elderly cardiogenic shock patients, estimated 1-year and 5-year survival rates were 38% and 24%.68 In an observational study of 61 patients greater than or equal to 75 years (mean age 79.5 ± 3 years) treated with primary PCI for AMI with cardiogenic shock, 56% of patients survived to hospital discharge, and the 30-day mortality was 47%. Of the survivors, 75% were alive at 1 year.69 In 55 octogenarians (mean age 84 ± 3 years) undergoing primary PCI for AMI, 30-day mortality was 4% in patients without cardiogenic shock and 70% in those with shock. The overall 1-year survival rate was 77%. Prasad71 prospectively evaluated whether physician judgment could be used to determine accurately which elderly shock patients would benefit from emergency PCI. These Mayo Clinic data confirmed that elderly patients selected by their physicians for PCI had better survival than those treated conservatively. Non-STEMI and Unstable Angina The optimal management of elderly patients with acute coronary syndrome has not been the subject of a dedicated clinical trial. Thus, the proper role of PCI can only be surmised from small series and subgroup analyses of larger studies. Ferguson72 published an experience of 88 consecutive patients over the age of eighty who had percutaneous coronary intervention for refractory angina. Procedural success was achieved in 86% with an in-hospital MACE rate of 7% (6/88). However, there were 3 in-hospital deaths in this group. The 30-day and 1-year MACE rates were 10% and 20%, respectively. During follow up, 59% remained free of angina, and only 6% required readmission for chest pain. In TIMI-3,73 advanced age was a stronger predictor of 6-month mortality than other clinical variables, including cardiac serum markers. Bach and colleagues74 retrospectively analyzed patients over the age of 75 enrolled in the TACTICS-TIMI 18 trial. The authors found that despite an increased risk of major bleeding, a routine early invasive strategy significantly improved the 30-day and 6-month outcomes, including death, nonfatal MI, rehospitalization, stroke and hemorrhage. The authors demonstrated that the early invasive strategy was associated with an absolute risk reduction of 4.8% compared with the conservative strategy (8.8% versus 13.6%; p = 0.018), and a relative reduction of 39% in death or MI at 6 months. Interestingly, the outcomes of the two strategies were similar among patients younger than 65 years of age. The positive findings of the TACTICS-TIMI 18 trial75 that are so widely publicized were primarily due to the elderly subgroup, a fact that is underappreciated. Age alone was not a determinant of outcome after PCI for acute coronary syndromes, but the combination of age with other comorbidities was a very powerful and dramatic predictor. Nevertheless, the critical message is that PCI can provide significant symptomatic relief in many elderly patients. Elective PCI Elective PCI in the elderly is the single clinical situation that has been tested in a dedicated, randomized clinical trial. This study is the TIME trial, which examined invasive versus medical therapy in elderly patients with chronic, symptomatic CAD.76 This is a randomized study of patients aged 75 years and older comparing an invasive strategy versus optimal medical therapy in patients with Canadian Classification Class II or higher (mean 3.2) who were on at least two anti-anginal medications. The mean age of patients in this study was 80 ± 4 years; 23% were diabetic and 44% were women. Endpoints included quality of life measures as well as MACE (death, nonfatal MI, recurrent ischemic events and acute coronary syndromes) at six months. In the initial publication, it was clear that there was significant crossover between those assigned to optimal medical therapy and those assigned to invasive therapy. Of the 150 patients randomized to optimal medical therapy, 37% ultimately underwent a coronary intervention on subsequent hospital admissions. Further, about 30% of those assigned to the invasive arm were actually treated medically. The primary endpoint of any MACE was substantially improved by undergoing invasive therapy and intervention anytime within the first year. This finding was present regardless of whether the initial management was invasive or medical. The benefit was primarily due to a decreased incidence of recurrent acute coronary syndromes. Death and nonfatal MI as a combined endpoint were no different, and, in fact, there was a trend toward an increased incidence of death in the invasive group. However, half of the deaths in the invasive group were in patients who were unwilling to undergo or deemed by the physicians to be unsuitable for coronary intervention or bypass surgery. In TIME, quality of life was evaluated using multiple scores and indices. There were no differences in the quality of life at baseline between those randomized to the invasive strategy versus those randomized to optimal medical therapy. At 6 months, all groups had an improved quality of life, but the invasive group enjoyed the largest increment in well-being. Hence, a strategy of early angiography and revascularization resulted in decreased MACE and improved quality of life compared to a conservative strategy of optimization of medical therapy in elderly patients with stable angina. However, the invasive strategy was associated with a trend toward increased mortality. Pfisterer77 expanded these results to one-year follow up. Improvements in angina and quality of life persisted in both therapies compared to baseline, but the early difference favoring invasive therapy disappeared. However, late hospitalization remained less frequent in the invasive group (10% versus 46%; p p 78 At this follow-up point, it is clear that MACE, especially nonfatal MI, were more frequent in the medically-treated group. Anginal relief and quality-of-life improvements were maintained in both groups equally. Revascularization within the first year improved survival in both invasive- and medically-assigned patients to a similar degree. TIME is highly commendable as a dedicated clinical trial interrogation, and adequately tested various strategies in elderly patients with CAD. The major problems with TIME are its relatively small size, compounded by the high cross-over rate. Consequently, there is inadequate power to determine the relative risk of cardiac mortality on the basis of initial strategy. Nevertheless, this excellent study is as convincing as any which will be performed in this subgroup of patients. Its conclusion is that a strategy of medical stabilization prior to revascularization for Classes III or IV angina is reasonable as long as the delay to revascularization is less than one year. Summary The elderly population is a rapidly growing segment of patients with coronary disease, and they present unique physiologic and anatomic problems. These patients are poorly represented in randomized clinical trials, hence management guidelines based on strong evidence are lacking. Elderly cardiac patients are treated less aggressively than younger patients in part because of the concern over an increased incidence of adverse events and complications. However, the lack of hard data on the relative therapeutic benefits of PCI compared to medical therapy renders it impossible to be certain what strategy is optimal in most clinical scenarios. The decision to perform PCI should not be based on chronologic age alone. Physiologic age and emotional health are extremely important considerations. The appropriate decision considers the significance of noncardiac comorbidities, the ability of the patient to purchase and tolerate drugs, the patient’s and family’s expectations of the outcome, and the technical feasibility of performing PCI. Enhancing personal independence and quality of life may be important goals of therapy, not just survival. PCI in the elderly carries a higher risk of acute coronary and other vascular complications. Age is clearly an independent risk factor for more complications and periprocedural mortality. However, the magnitude of risk depends strongly on the presence and severity of associated angiographic and clinical factors associated with increased risk in every patient undergoing PCI, especially comorbidities. Characterization as “elderly” using whatever age cutoff is appropriate does constitute a high-risk variable. PCI in the elderly improves quality of life, but there may be an early cost in morbidity to achieve this outcome. Therefore a critical and conservative assessment of strategy and risk assessment is appropriate. Careful case selection using sound clinical judgment based on the patient’s pre-illness mental status, physical condition, and quality of life is of paramount importance. Additionally, to further improve outcomes of PCI, interventionists should be mindful of the most likely complications and perform these procedures with attention to detail. The management of these patients would be improved with more studies in specific circumstances. These would ideally include studies dedicated to determining: (1) the outcomes in different age groups within the elderly population; (2) how to better select cases based on mental status and activity level; and (3) which comorbid conditions and clinical factors predict high risk, and conversely, those patients most likely to benefit from PCI. Most critical is the need for specifically designed trials (and not merely post hoc subgroup analyses of PCI outcomes) in patients with particular clinical presentations of ischemic heart disease.
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