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By its definition, chronic stable coronary artery disease (CAD) refers predominantly to patients who have a prior history of or current demonstrable obstructive atherosclerotic disease of the epicardial coronary arteries and who are either asymptomatic, or have stable symptoms, with no evidence of recent symptomatic, hemodynamic, or electrical decompensation. Because the process of atherosclerosis usually evolves over several decades, the natural history of CAD typically involves long periods during which patients are asymptomatic, minimally symptomatic, or have stable symptoms that can be effectively managed; however, these periods of clinical stability can rapidly transition to acute coronary syndromes (ACSs), resulting in serious, and sometimes fatal, adverse cardiac events. The major goals of treating patients with chronic stable CAD are, therefore, 2-fold. One is to prolong life and prevent or reduce major adverse cardiovascular events. The second, and equally important, goal is to control symptoms of CAD—primarily angina—with the purpose of improving symptoms, functional status, and quality of life, as well as reducing hospitalizations. These goals are achieved, in part, by administering evidence-based medical therapies that have been proven to provide prognostic benefit, improve symptoms of angina, or achieve both goals; and by identifying (through appropriate testing) a subgroup of patients that may derive a prognostic benefit from coronary revascularization. This section will summarize the key therapeutic approaches to achieving these goals and direct the reader to additional details for each of the treatment strategies in other chapters.
Improving Survival and Prevention of Major Adverse Cardiac Events
Lifestyle Interventions
Numerous prior studies have documented the positive impact of dietary interventions and physical activity on surrogate markers of cardiovascular risk (such as blood pressure, lipids, blood glucose, and weight), and meta-analyses suggest that an intensive lifestyle intervention program may have a modest beneficial effect on cardiovascular mortality and prevention of myocardial infarction (MI). Multiple beneficial effects of cardiac rehabilitation programs have also been demonstrated in several prior studies, and they are endorsed by professional guidelines in patients who have sustained an ACS or have had a revascularization procedure. See Chapter 18 for more on this topic.
Medical Therapy
Few treatment approaches have been definitively shown to reduce mortality and prevent Major Adverse Cardiac Events (MACE) in patients with chronic stable CAD. Although β-blockers are a mainstay of therapy in chronic stable CAD, little evidence exists that their prolonged use results in improved survival or lower MACE rate. A meta-analysis of older clinical trials demonstrated an overall 23% relative risk reduction in mortality in patients following acute MI; however, this meta-analysis primarily included studies performed before the modern era of coronary revascularization/reperfusion and medical therapy and did not examine truly long-term treatment (median duration of follow-up was 1.4 years). Data from the REduction of Atherothrombosis for Continued Health (REACH) registry, which included over 20,000 propensity-matched patients that were and were not treated with β-blockers, demonstrated no statistically significant difference in the rates of MACE between patients with established CAD and no prior MI during a median follow up of nearly 4 years. Among patients with previous history of MI, the outcomes were numerically favorable in patients with versus without β-blocker use, but this difference was not statistically significant. Other large observational studies also suggest a modest benefit in patients with a recent MI, but not in those without prior acute MI. As a result, current guidelines for chronic stable CAD management give a strong recommendation for the use of β-blockers in patients with prior MI or history of heart failure, but not in other patients with chronic stable CAD.
Other medical therapies used for treating symptoms of CAD, such as calcium-channel blockers, nitrates, and ranolazine, have not been shown to have an effect on survival or MACE events. In randomized clinical trials, neither nifedipine nor amlodipine was shown to reduce the rates of cardiovascular death or MI. In the Metabolic Efficiency with Ranolazine for Less Ischemia in Non−ST-Elevation Acute Coronary Syndromes (MERLIN-TIMI36) trial, which was performed in patients stabilized after an ACS event, ranolazine did not significantly reduce the primary endpoint of cardiovascular death, MI, or recurrent ischemia compared with placebo. No cardiovascular outcomes trials have ever been performed with long- or short-acting nitrates in this patient population.
Antiplatelet therapy has been proven to improve outcomes in patients with established CAD and is endorsed by practice guidelines. The Antithrombotic Trialists’ Collaboration meta-analysis of over 135,000 patients, which included those with prior vascular events but also patients with previous coronary revascularization procedures and/or stable angina, demonstrated a significant reduction in MACE (nonfatal MI, nonfatal stroke, or vascular death) with antiplatelet therapy, primarily aspirin There was no difference in efficacy or safety between low-dose (75 to 150 mg daily) and higher-dose aspirin. The use of thienopyridines, such as clopidogrel, instead of aspirin may provide an additional modest benefit, but is not recommended unless patients are unable to tolerate aspirin. The use of dual antiplatelet therapy (aspirin plus P2Y12 receptor blocker) in patients with chronic stable CAD (and without another indication, such as recent coronary stent implantation) is more controversial; an in-depth discussion of antiplatelet therapy, as well as anticoagulants, is provided in Chapter 21 .
Lowering of low-density lipoprotein cholesterol (LDL-C) with statin therapy is a mainstay of chronic stable CAD management. Numerous clinical trials and multiple meta-analyses have demonstrated the benefits of LDL-C lowering—specifically with statins—on cardiovascular outcomes. Specifically, both in trials of statins versus placebo, and in trials of more intensive versus less intensive statin regimens, a consistent benefit of intensive statin therapy is observed in patients with established CAD, including reductions in cardiovascular and all-cause mortality, and MI, and, therefore, clinical guidelines strongly endorse high-intensity statin treatment for all eligible patients with established CAD. For patients with established CAD that require additional LDL lowering despite maximally tolerated statin therapy, several options for nonstatin LDL-C lowering exist; however, only ezetimibe has been shown to provide additional, modest clinical benefit in combination with a statin. Of note, the modest benefit with ezetimibe was observed in patients in whom treatment was initiated following an ACS event and was predominantly seen in the subgroup of patients with type 2 diabetes; whether these data can be extrapolated to patients with chronic stable CAD without prior ACS is unclear. Therapies aimed at raising high-density lipoprotein (HDL) and/or lowering triglycerides have so far failed to provide additional clinical benefit in recent clinical trials. The effects of LDL cholesterol lowering therapies in patients with established CAD are discussed in detail elsewhere ( Chapter 30 ).
In the broad population of patients with stable CAD, angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), and mineralocorticoid receptor antagonists have not been consistently demonstrated to improve outcomes above and beyond blood pressure lowering; however, these agents have important benefits (including reduction in total mortality, MI, stroke, and heart failure) in several key subgroups of patients, such as those after acute MI with reduced left ventricular ejection fraction (LVEF), symptomatic heart failure, and high-risk diabetes, and may also improve renal outcomes in patients with chronic kidney disease (CKD) (particularly diabetic nephropathy). Medical therapy is discussed in more detail in Chapter 20 .
Coronary Revascularization
A benefit of coronary revascularization ( Chapter 23 ) on death and MI has been difficult to demonstrate in patients with stable CAD, except in select patient populations (high-grade left main disease, multivessel disease with reduced LVEF and/or large ischemic burden, etc.) in whom coronary artery bypass graft (CABG) surgery is indicated. Percutaneous coronary intervention (PCI), even with the latest generation drug-eluting stents, has not been shown to improve the natural history of stable CAD. This contrasts with evidence in patients with ACS, where routine use of PCI lowers the risk of recurrent ischemic events.
An important goal of management is to identify the minority of patients with stable ischemic heart disease (IHD) who have clear indications for coronary revascularization. Multiple noninvasive testing options are available for risk stratification, including standard stress electrocardiography ( Chapter 10 ), echocardiography and stress echocardiography ( Chapter 11 ), nuclear and positron emission tomography (PET) imaging ( Chapter 12 ) and cardiac computed tomography (CT), and magnetic resonance imaging (MRI) ( Chapter 13 ). Selection among the different testing options should be based on individual patient factors, local expertise, and cost considerations. ( Chapter 15 ). When high-risk findings are found on noninvasive testing, coronary angiography is generally indicated. Incorporation of functional assessment of the impact of coronary stenoses using hemodynamic assessments such as fractional flow reserve ( Chapter 14 ) improves decision-making regarding coronary revascularization, allowing deferral of revascularization for lesions with minimal hemodynamic significance.
Improving Symptoms and Quality of Life
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