Revascularization in Non–ST-Elevation Acute Coronary Syndrome: For Whom, When, and How?

Introduction

A non–ST-elevation acute coronary syndrome (NSTE-ACS) is caused by a severe flow-limiting stenosis or acute thrombotic obstruction of a coronary artery (see Chapter 13 ). In the absolute majority of cases,levels of myocardial markers also are elevated, indicating myocardial damage related to thrombotic obstruction at the site of the culprit coronary lesion, as well as to downstream embolization of thrombotic material from the lesion. The thrombotic component of the disease can be influenced by treatment with anticoagulant and antiplatelet agents (see Chapter 18 and Chapter 19 ). Most often, however, one or more severe coronary stenoses remain, with consequent high risk for recurrent events during or after withdrawal of the initially intense antithrombotic treatment. Intervention to improve coronary flow is the rationale for early use of coronary angiography and revascularization.

Elimination or bypass of the flow-limiting lesions by means of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) complements medical therapy for rapid initial as well as long-term stabilization of the patient’s condition. The benefits and risks are related not only to lesion characteristics but also to patient characteristics that affect the progression of atherothrombosis and the risk of complications with these invasive procedures (see Chapter 17 ). Early risk stratification (see Chapter 11 ) is important to identify patients at high immediate- and long-term risk for death and cardiovascular events, in whom an early invasive strategy with adjunctive medical therapy may reduce that risk.

Coronary Angiography

Invasive coronary angiography, followed by coronary revascularization, is performed in a majority of patients hospitalized with NSTE-ACS in geographic regions with well-developed health care systems. The decision for an invasive strategy should carefully weigh the risks of invasive diagnostics and the potential benefits. The decision to proceed with coronary revascularization, once the anatomy is defined by angiography, takes into account the risk in terms of morbidity and mortality associated with the proposed procedure (PCI or CABG) and the benefits in terms of short- and long-term prognosis, symptom relief, quality of life, and duration of hospital stay.

In the vast majority of cases, coronary angiography allows clinicians to achieve the following:

• Confirm the diagnosis of ACS related to obstructive epicardial coronary artery disease (CAD) (or rule out epicardial CAD as the origin of chest pain).

• Guide subsequent antithrombotic treatment or avoid unnecessary exposure to antithrombotic agents.

• Identify the culprit lesion(s).

• Establish an indication for coronary revascularization and assess the suitability of coronary anatomy for PCI and CABG.

• Stratify the patient’s short- and long-term risk.

Angiographic patterns of CAD in patients with NSTE-ACS are diverse, ranging from a normal appearance of epicardial coronary arteries to a severely and diffusely diseased coronary artery tree. In patients with a clinical diagnosis of ACS, approximately 10% will be found to have disease of the left main artery, 25% will have three-vessel disease, 25% will have two-vessel disease, 25% will have one-vessel disease, and 15% will have no significant CAD at coronary angiography. Risk indicators such as age, male gender, diabetes mellitus, previous myocardial infarction (MI), previous severe angina, renal dysfunction, left ventricular dysfunction (manifesting as elevated B-type natriuretic peptide), ST-segment depression, elevated troponins, elevated growth differentiation factor 15 (GDF15), and higher risk response on stress testing are associated with a higher likelihood of multivessel or left main coronary artery disease (see Chapter 11 ). However, the correlations between the extent of CAD and these risk indicators are rather weak.

Routine Invasive Versus Selective Invasive Management

Multiple clinical trials and meta-analyses have compared a routine invasive versus selective invasive management strategy in patients with NSTE-ACS. Compared with a selective invasive strategy, a routine invasive strategy improves clinical outcomes and reduces rates of recurrent ACS, subsequent rehospitalization, and revascularization ( Figure 16-1A-C ). The FRISC-2, TACTICS-TIMI 18, and the RITA-3 trials were the first three trials in which patients received contemporary antithrombotic therapy, and most of the revascularization procedures were either PCI with routine stenting or CABG. All three trials demonstrated a reduction in the composite of death, MI, and recurrent severe angina, with a routine invasive strategy compared with a primarily conservative (selective invasive) treatment. Although an early hazard with more procedure-related MIs during hospitalization was noted for FRISC-2 and TACTICS-TIMI 18, a reduction of death and MI was seen in the intermediate term on follow-up evaluation at 6 months. In long-term follow-up extending to 5 years, other benefits included persistent reduction in the composite of death and MI and a trend toward improved overall survival (see Figure 16-1A-C ).

Somewhat surprisingly, the ICTUS trial, performed in a population of patients with troponin-positive NSTE-ACS, demonstrated no advantage with an early invasive approach over a more selective approach with revascularization only in those with ischemia at rest or exercise (see Figure 16-1D ). However, the differing outcome in this trial compared with that in the other two is likely to be explained by a substantial crossover of 44% of patients receiving the noninvasive management to an invasive intervention.

Across the multiple trials of early invasive versus conservative management, the proportion of patients undergoing revascularization in the different trials varied markedly. In some trials, less than 50% of patients in the invasive arm underwent early revascularization procedures, compared with a 35% to 45% early revascularization rate in the noninvasive arm ( Figure 16-2 ). Consequently, the ability to demonstrate a mortality benefit with routine revascularization may depend on the difference in revascularization rate between randomized arms ( Figure 16-3 ).

Furthermore, the true benefit of a routine invasive treatment shown in trials probably is underestimated—not only because revascularization was allowed when patients deteriorated while on medical therapy (crossover) but also because trials excluded those with very-high-risk features and did not include consecutive patients. When the ICTUS trial began enrolling patients, the availability of results from previous trials might have increased the likelihood of excluding high-risk patients from the trial by sending them directly to invasive treatment.