High Risk Versus Futility in Revascularization of Patients With SIHD


The aging of the population of the United States and other industrialized nations has led to burgeoning numbers of elderly patients with atherosclerotic cardiovascular disease (ASCVD). Age-related changes in endothelial function, inflammation, and vascular stiffness, in combination with increasing prevalence and duration of exposure to traditional cardiovascular risk factors, result in greater incidence of ASCVD with increasing age in both men and women.1

Older patients tend to have more extensive coronary atherosclerosis,2 often presenting with multivessel and left main disease. Consequently, a third of all myocardial infarctions (MI) and more than half of deaths attributable to MI occur in patients 75 years and older.3 In addition to being a leading cause of mortality in older adults, coronary atherosclerotic disease is a major cause of disability, loss of independence, and poor quality of life.4

Management of Stable Ischemic Heart Disease

The cornerstone of management of stable ischemic heart disease (SIHD) is risk assessment and guideline-directed medical therapy. The most recent 2012 American College of Cardiology and American Heart Association guidelines recommend stress testing for patients suspected of having SIHD to secure the diagnosis and obtain prognostic information. Additionally, the 2014 focused update recommends coronary angiography for patients with presumed SIHD with refractory symptoms despite medical therapy who may benefit from revascularization.5

Medical therapy for patients with SIHD centers on three classes of antianginal drugs: beta-blockers, calcium channel blockers, and nitrates. Beta-blockers are first line therapy for the reduction of angina symptoms and the improvement of exercise tolerance. They are the only antianginal drugs proven to prevent reinfarction and to improve mortality in patients with a history of MI.6

In addition to alleviating symptoms, optimal medical management of patients with stable angina must include risk factor modification. Patients should be treated for hypertension, hyperlipidemia, weight reduction, smoking cessation, and glycemic control if they are diabetics. They should be counseled to participate in regular aerobic exercise. All patients at increased risk of an occlusive vascular event should be treated with aspirin unless they have a contraindication.7

The two primary goals of coronary revascularization are relief of refractory symptoms and improvement of life expectancy. Thus, patients with angina that interferes with their quality of life despite maximal tolerable medical therapy and those who present with high-risk criteria on noninvasive testing should be referred for coronary angiography. An example of the latter scenario is a patient with reduced left ventricular (LV) systolic function with evidence of multivessel disease on stress myocardial perfusion imaging. Prior to referral, however, clinicians should delineate the goals of treatment. Often, elderly patients are more interested in maintaining quality of life and functional independence than pursuing longevity. Although this may mean a higher threshold for recommending invasive treatment for asymptomatic ischemia, studies have shown improved quality of life for elderly patients with persistent angina who undergo revascularization.8,9

Choosing a Modality of Revascularization: PCI Versus CABG

The complexity of disease and number of affected vessels, likelihood of achieving complete revascularization, functional status, comorbid diseases, and patient preference should all be taken into account when choosing between percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG).

The BARI (Bypass Angioplasty Revascularization Investigation) study was an early randomized trial comparing outcomes of CABG and PCI with bare-metal stents. Of nearly 2,000 patients with symptomatic multivessel coronary artery disease (CAD), 709 (39%) were 65-80 years old at the time of enrollment. Subgroup analysis of these patients demonstrated higher rates of stroke after CABG and more incident heart failure or pulmonary edema after PCI with no significant difference in cardiac death at 5 years among those without diabetes.10

The AWESOME (Angina with Extremely Serious Operative Mortality Evaluation) trial was a multicenter Veterans Affairs randomized trial and registry comparing CABG and PCI with bare-metal stents for treatment of patients with refractory myocardial ischemia who were considered to be at higher risk for an adverse outcome with surgery. More than half the subjects were greater than 70 years of age. Subgroup analysis of these patients showed comparable survival in both treatment arms at 5 years.11

Since the development of drug-eluting stents, numerous studies comparing outcomes of PCI and CABG have shown no difference in outcomes such as mortality and MI, but the studies were mostly small and nonrandomized.12-14

The SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) study is the only large randomized controlled trial to compare outcomes of PCI with a first-generation drug-eluting stent and CABG in patients with three-vessel or left main CAD.15 At 5 years of follow-up, there were higher rates of MI and repeat revascularization in patients treated with PCI rather than CABG but no difference in mortality. Among patients with low SYNTAX scores (reflecting lower complexity of disease) and with left main disease (low or intermediate SYNTAX score), there was no difference in major adverse cardiovascular events between treatment arms; however, in patients with intermediate or high SYNTAX scores, outcomes were significantly improved with CABG.16

The currently available body of evidence suggests that CABG should be the preferred modality of revascularization for those with complex, diffuse CAD, whereas patients with uncomplicated and less-extensive disease will have comparable survival rates with either CABG or PCI.

Left Main Disease

Left main disease is seen in about 5% of patients undergoing coronary angiography and often occurs in the setting of extensive overall disease. Due to the large myocardial territory at risk, left main disease is associated with high mortality. Early studies showed better outcomes with CABG compared with medical therapy, with PCI previously reserved for poor surgical candidates. Current guidelines recommend that most patients with left main CAD undergo CABG. In the SYNTAX trial, 705 of a total of 1,800 patients presented with left main disease. At 5 years, patients with the highest SYNTAX scores (reflecting greater severity and complexity of disease) had lower mortality and a lower rate of repeat revascularization with CABG. However, patients with left main disease with low to intermediate SYNTAX scores had a lower mortality and stroke rate with PCI.17

Two recent randomized trials sought to address the question of which method of revascularization is best for treating left main disease. The EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) study randomized patients with obstructive left main CAD and low or intermediate SYNTAX scores to either CABG or PCI with a second-generation drug-eluting stent. At 3 years, PCI with everolimus-eluting stents was shown to be non-inferior to CABG with respect to rate of death, stroke, or MI.18 NOBLE (Nordic–Baltic–British Left Main Revascularisation Study) enrolled patients with left main disease and no more than three additional non-complex lesions. The SYNTAX score was not utilized to stratify patients. At 5 years, patients randomized to CABG had superior outcomes with regard to MI, stroke, and repeat revascularization. In NOBLE, outcomes were the same in both treatment arms at 1 year; thus, one conclusion is that PCI, given its less-invasive nature, may be preferable in patients with limited life expectancy.19

Multivessel Disease

MASS II (Medicine, Angioplasty, or Surgery Study) randomized over 600 patients with stable multivessel CAD and preserved LV systolic function at a single center to optimal medical therapy alone or concurrent with revascularization by either CABG or PCI. After 10 years of follow-up, there was a significantly higher rate of repeat revascularization and MI in the medical therapy and PCI arms but no difference in all-cause mortality. Subgroup analysis of patients older than 65 years showed a significantly lower rate of the composite endpoint of MI, revascularization, and all-cause mortality in those treated with CABG rather than with PCI or medical therapy alone.20

In a review of data from the New York State registries for PCI and CABG, in patients with multivessel disease and reduced LV systolic function, patients who undergo PCI with implantation of a second-generation drug-eluting stent have rates of survival similar to those treated with CABG.21 CABG is associated with higher upfront risk of stroke, whereas PCI is associated with higher risk of repeat revascularization and perhaps MI (in those with incomplete revascularization). In selected patients with LV dysfunction, PCI with newer-generation drug-eluting stents may be an acceptable alternative to CABG when complete revascularization is feasible.

Chronic Total Occlusions

A chronic total occlusion (CTO) is defined as a 100% obstructive coronary lesion present for at least 3 months with less than or equal to Thrombosis in Myocardial Infarction Grade I flow. The estimated prevalence of CTOs is around 30% in high-risk patients referred for coronary angiography.22,23 Patients with a CTO often have stable exertional angina resulting from insufficient blood flow through collaterals to meet myocardial oxygen demand during stress.24 In addition to improvement of symptoms, consideration of revascularization may be prompted by significant ischemia on noninvasive imaging.

Although CTOs are prevalent in patients with known CAD, the rate of attempted interventions on these lesions varies greatly depending on geographic location and regional practice patterns. An analysis of procedural outcomes in elective patients between 2009 and 2013 in the National Cardiovascular Data Registry demonstrated that CTO PCI comprised 3.8% of interventions performed for stable CAD. The procedural success rate was 59% compared with 96% in those without CTOs.25-27 Given the inherent complexity and technical challenges of CTO PCI, patients who may benefit from these interventions should be referred to high volume centers with experienced operators.

TOAST-GISE (Total Occlusion Angioplasty Study-Società Italiana di Cardiologia Invasiva) was a prospective, observational study that sought to describe the impact of CTO PCI on relief of angina in 376 consecutive patients. At 1 year of follow-up, patients who had successful revascularization reported significantly less angina and were more likely to complete an exercise stress test without limiting symptoms than their counterparts whose PCI was unsuccessful.28

Subsequently, the FACTOR (FlowCardia's Approach to Chronic Total Occlusion Recanalization) trial enrolled 125 patients undergoing CTO PCI and tracked patient-reported health status using the Seattle Angina Questionnaire. At 30-day follow-up, mean scores for angina frequency, physical limitation, and quality of life were significantly improved in patients whose CTO PCI ended in successful recanalization compared with those whose procedures were unsuccessful.29

The SYNTAX trial showed that incomplete revascularization is associated with greater mortality, major adverse cardiac events, and cerebrovascular events in patients treated with either PCI or CABG.30 The adverse clinical outcomes associated with incomplete revascularization are strongly predicted by the presence of a total occlusion.

Guideline Recommendations

Current guidelines recommend CABG to improve survival in patients with significant triple vessel CAD or double vessel disease involving the proximal left anterior descending artery. Patients with diabetes and multivessel CAD are recommended to undergo CABG in preference to PCI, particularly if a left internal mammary artery graft can be anastomosed to the left anterior descending artery. Revascularization of significant coronary lesions by either modality is reasonable to improve symptoms in patients with refractory angina despite medical therapy.


When approaching a complex patient considering a high-risk attempt at revascularization, it is helpful to assess his or her frailty status. Frailty is a biological syndrome reflecting decreased physiological reserve with subsequent vulnerability to stressors. There are numerous assessment tools for measuring frailty. The Fried scale is the most frequently utilized in clinical research and is a multi-item scale incorporating slow walking speed, weakness, low physical activity, exhaustion, and unintentional weight loss.31 It has been shown to predict mortality and morbidity in community-dwelling elderly persons and in patients with cardiovascular disease. Frail persons with cardiovascular disease have a twofold increase in mortality after adjustment for age and comorbidities.32 Incorporating an assessment of a patient's frailty status into management of his or her cardiovascular disease can enable a physician to provide care in a more patient-oriented manner.


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