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Chronic coronary syndrome: Indications for revascularization

Chronic coronary syndrome: Indications for revascularization
Author:
Thomas Levin, MD
Section Editor:
Donald Cutlip, MD
Deputy Editor:
Todd F Dardas, MD, MS
Literature review current through: Jan 2024.
This topic last updated: Oct 03, 2023.

INTRODUCTION — The goals of therapy in patients with chronic coronary syndrome (also referred to as stable angina or stable ischemic heart disease) are to alleviate symptoms and decrease the risk of adverse cardiovascular outcomes such as death, heart failure, or myocardial infarction. To these ends, all patients should receive optimal medical therapy, which is discussed in detail elsewhere. (See "Chronic coronary syndrome: Overview of care".)

This topic will review the evidence comparing optimal medical therapy with revascularization plus optimal medical therapy in patients with chronic coronary syndrome. The choice between percutaneous coronary intervention and coronary artery bypass graft surgery, when revascularization is required, is discussed separately. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

The role of revascularization in patients with acute coronary syndromes (eg, myocardial infarction and unstable angina) is discussed elsewhere. (See "Overview of the acute management of ST-elevation myocardial infarction", section on 'Choosing and initiating reperfusion with PCI or fibrinolysis' and "Overview of the acute management of non-ST-elevation acute coronary syndromes", section on 'Choosing a revascularization strategy'.)

ROLE OF DIAGNOSTIC TESTING — All patients with stable angina should undergo cardiac stress testing, in part to identify those individuals who are likely to benefit from revascularization. Stress testing is indicated soon after the diagnosis is made or if there is a major change in symptoms status. (See "Selecting the optimal cardiac stress test", section on 'Indications for stress testing'.)

Diagnostic coronary angiography should be performed if the information obtained might lead to a decision to perform revascularization. Specific indications for the performance of this test in patients with chronic coronary syndrome are discussed separately. (See "Chronic coronary syndrome: Overview of care", section on 'Identifying patients for angiography and revascularization'.)

INDICATIONS — Revascularization with either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI), as opposed to continuing medical therapy without revascularization, is indicated in two groups of stable patients:

Patients with specific high-risk anatomy for which revascularization has a proven survival benefit.

Patients who want revascularization for improved quality of life compared with medical therapy, such as those who are not tolerating medical therapy well or who want to increase their activity level.

There is also some evidence of benefit for revascularization in patients with at least moderate myocardial territory ischemia.

Patients with high-risk anatomy — Survival is improved by CABG over optimal medical therapy in patients with severe coronary artery disease who have coronary artery disease that places them at high risk for an adverse cardiovascular event because of a large amount of myocardium supplied by the diseased vessel(s) or because of significant underlying left ventricular dysfunction. These include patients with:

Left main coronary artery stenosis or left main equivalent disease. (See "Left main coronary artery disease".)

Three-vessel coronary artery disease, particularly with a reduced left ventricular ejection fraction (usually <40 percent) [1-5]. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Multivessel disease'.)

There is no convincing evidence that revascularization of isolated severe proximal left anterior descending (LAD) coronary artery disease improves survival. However, many of our experts prefer revascularization of proximal LAD stenosis in patients with confirmed ischemia. This issue is discussed separately. (See "Management of significant proximal left anterior descending coronary artery disease".)

The evidence of survival benefit with revascularization comes principally from older studies of patients undergoing CABG. Since most of the evidence favoring CABG was obtained before contemporary PCI and standard use of optimal medical therapy, these options are also evolving and require individualized decision-making based on anatomy, clinical setting, and procedural risk. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Relief of angina — For many patients who have not had adequate control of anginal symptoms with optimal medical therapy, revascularization may improve symptom status [6,7].

The 2020 ISCHEMIA trial randomized patients with chronic coronary disease to revascularization (PCI or CABG) plus medical therapy and lifestyle changes or to an initial strategy of medical therapy and lifestyle change. Although this trial did not show a reduction in death or myocardial infarction, ISCHEMIA confirmed that an early invasive strategy resulted in better symptom relief and angina-related quality of life [8]. Among those with daily or weekly angina at the start of the study, 45 percent of those who were randomized to revascularization and medical therapy were angina-free after a year, compared with 15 percent of those treated with medical therapy alone. Improvements in angina-related quality of life persisted for four years in ISCHEMIA, among those who had at least weekly angina at baseline.

However, the 2017 ORBITA trial did not find that angina was reduced by revascularization. This trial randomly assigned 230 patients with angina and severe (≥70 percent) single-vessel stenosis to PCI with a current-generation DES or a placebo procedure after six weeks of medical therapy optimization [9]. Evaluation with exercise testing, symptom questionnaires, and dobutamine stress echocardiography was performed before randomization and at six-week follow-up. There was no significant difference between the two groups in the primary endpoint of exercise time increment (28.4 versus 11.8 seconds, respectively; difference in increment between groups 16.6 seconds, 95% CI -8.9 to 42 seconds; p = 0.200). Similarly, there were no differences in the rates of other exercise variables or patient-reported anginal symptoms. Prior studies have suggested that interventions that improve exercise time by more than 30 seconds are clinically relevant.

PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFT SURGERY — A detailed discussion of when to choose percutaneous coronary intervention or coronary artery bypass graft surgery is found elsewhere. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Summary and recommendations' and 'Indications' above.)

PATIENTS WITHOUT CLEAR INDICATIONS — In some patients with stable coronary artery disease, the choice between revascularization and optimal medical therapy is not clear. This section will provide some guidance.

Uncertain efficacy of revascularization — Studies that have evaluated a potential benefit of revascularization have included patients with a broad spectrum of disease severity; more recent studies have focused on those without high-risk anatomy such as left main disease.

A 2021 meta-analysis demonstrated a reduction in cardiac deaths and new acute myocardial infarctions with revascularization [10]. This study included 25 clinical trials (n = 19,806 patients) of revascularization (with either CABG or PCI) plus medical therapy versus medical therapy alone. Individuals randomized to elective coronary revascularization had reduced cardiac mortality (RR 0.79, 95% CI 0.67-0.93). The survival benefit after revascularization improved with longer follow-up times and was also associated with fewer spontaneous myocardial infarctions (RR 0.74, 95% CI 0.64-0.86). Other clinical trials and meta-analyses comparing optimal medical therapy with PCI have suggested a possible benefit in reduced spontaneous MI and urgent revascularization from PCI [11-16].

These findings contrast with those of individual studies that found only a limited and uncertain benefit for PCI. In the 2007 COURAGE trial, no significant difference in survival was found between patients assigned to either optimal medical therapy alone versus aggressive medical therapy plus PCI with bare-metal stents [17,18]. In the 2020 ISCHEMIA trial, 5179 patients with chronic coronary syndrome were treated with an early invasive strategy with revascularization (PCI or CABG) plus medical therapy and lifestyle changes or with an initial strategy of medical therapy and lifestyle change [19]. Revascularization was reserved for treatment failure. At five years, cardiac events and mortality were similar in the two treatment groups. In ISCHEMIA, rates of spontaneous myocardial infarctions were reduced with PCI, although rates of procedural myocardial infarctions were higher in the group that received PCI. Individuals in the revascularization arm had less angina. (See 'Relief of angina' above.)

Patient preference — After a thorough discussion of the potential benefits and risks of revascularization, patient preference becomes important for those who are not found to have anatomy that mandates revascularization based on a survival benefit. (See 'Indications' above.)

This discussion should take place before diagnostic coronary angiography, since percutaneous coronary intervention (PCI) is often performed immediately after in part so that the patient does not have to undergo two invasive procedures. The discussion should emphasize both the benefits of PCI (eg, less angina and a lower likelihood of requiring an intervention in the first few years) and the drawbacks of PCI, including the inherent risks of the procedure and the potential problems of long-term clopidogrel therapy. (See "Coronary artery stent thrombosis: Incidence and risk factors" and "Periprocedural complications of percutaneous coronary intervention".)

In some cases, the indication for revascularization or the decision between PCI and coronary artery bypass graft surgery (CABG) are less clear. It is important to have additional discussions with the patient after diagnostic angiography and before proceeding with PCI. In those cases that may be considered for PCI or CABG, we agree with the concept of the "heart team" to fully discuss the risks and benefits of both PCI and CABG, as well as optimal medical therapy. We support the "heart team" approach to decision-making, in which an interventional cardiologist, cardiac surgeon, and other health care professionals discuss revascularization options with the patient in advance of the procedure [20,21].

Severity of coronary artery disease — Among patients with chronic coronary syndrome who have unclear indications for PCI (eg, intermediate coronary artery narrowing of 50 to 70 percent diameter by visual estimate), the severity and extent of atherosclerotic narrowing in a coronary artery can be assessed with intravascular ultrasound (IVUS) and using coronary flow pressure measurement. IVUS provides intracoronary imaging and can assess plaque anatomic characteristics, whereas coronary pressure artery pressure flow is a physiology-based assessment that allows calculation of the fractional flow reserve (FFR); the FFR is calculated from catheter-based pressure measurements taken proximal and distal to the coronary artery obstruction. (See "Clinical use of coronary artery pressure flow measurements" and "Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation", section on 'IVUS clinical applications'.)

FFR – There is some evidence that in patients with more severe coronary artery disease, but who do not meet criteria for CABG, outcomes are better with PCI than optimal medical therapy. In the FAME 2 randomized trial, patients with stable coronary artery disease who were being considered for PCI underwent diagnostic coronary angiography and subsequent evaluation of all stenoses that were thought to be angiographically significant with FFR measurement [14]. (See "Clinical use of coronary artery pressure flow measurements", section on 'Multivessel disease'.)

Patients with at least one stenosis in a major coronary artery with an FFR of 0.80 or less were randomly assigned to FFR-guided PCI (all stenoses with FFR ≤0.80 were treated with a drug-eluting stent) plus best medical therapy or best medical therapy alone. The primary endpoint was a composite of death, myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 24 months. The study was stopped early (after randomization of 888 of the projected 1632 patients) by the data and safety monitoring board. After a mean duration of follow-up of 213 days, the primary endpoint occurred less often in patients who underwent PCI (4.3 versus 12.7 percent; hazard ratio [HR] 0.32, 95% CI 0.19-0.53). At two-year follow-up, the rate of the primary endpoint was lower in the PCI group (8.1 versus 19.5 percent; HR 0.39, 95% CI 0.26-0.57) [22]. This result was driven by a lower rate of urgent revascularization in the PCI group (4 versus 16.3 percent; HR 0.23, 95% CI 0.14-0.38). The results were similar at five years [23].

Important limitations of FAME 2 include the absence of noninvasive documentation of ischemia prior to diagnostic coronary angiography, the possibility (in the absence of blinding) that the threshold for referring patients for PCI was lower in the medical therapy group, and the fact that it was stopped early [24]. Despite these limitations, we believe FAME 2 supports the use of PCI in patients with documented ischemia involving at least a moderate myocardial territory. We prefer to limit the use of FFR in this setting to intermediate lesions (50 to 70 percent diameter stenosis by visual estimate) or cases where the documentation of at least moderate ischemia is equivocal.

FFR versus IVUS – We use FFR to guide PCI in patients with intermediate-risk coronary disease and reserve IVUS as a complementary modality to assess plaque anatomy. One randomized trial supports this approach [25]. In the FLAVOUR Trial of 1682 patients with chronic coronary syndrome and intermediate stenosis who were being evaluated for PCI, patients who were assigned guidance by FFR compared with IVUS had a similar risk of death, myocardial infarction, or revascularization at 24-month follow up (absolute difference, -0.4 percentage points) [25]. The study also reported the following:

Intermediate stenosis was 40 to 70 percent visual occlusion on coronary angiography.

Patients underwent PCI if FFR was ≤0.8, or if upon IVUS, the minimal lumen area measured ≤3 mm2 or 3 to 4 mm2 with a plaque burden or >70 percent.

Less patients in the FFR group were guided to PCI compared with the IVUS group (44.4 versus 65.3 percent).

Patient-reported angina as reported on the Seattle Angina Questionnaire was similar in the two groups.

Reduced left ventricular systolic function — For the most part, patients enrolled in the randomized trials discussed above have had normal or near normal left ventricular systolic function. The role of revascularization in patients with ischemic cardiomyopathy is discussed separately. (See "Treatment of ischemic cardiomyopathy".)

Patients with diabetes — While the indications for revascularization are similar for patients with and without diabetes, there is evidence to prefer CABG to PCI in those with multivessel disease. This issue is discussed separately. (See "Coronary artery revascularization in stable patients with diabetes mellitus", section on 'PCI versus CABG'.)

Advanced chronic kidney disease — Revascularization has an uncertain role in the management of patients with chronic coronary syndrome and advanced chronic kidney disease (CKD).

Among patients with chronic coronary syndrome, advanced CKD (estimated glomerular filtration rate <30 or on dialysis), and moderate or severe ischemia, an initial invasive strategy did not reduce cardiovascular disease events or angina-related quality of life but was associated with more stroke and death or starting dialysis. In the ISCHEMIA-CKD trial, 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing were randomized to initial invasive strategy of coronary angiography and revascularization added to medical therapy versus conservative medical therapy alone [26]. At a median follow-up of 2.2 years, a primary outcome event (composite of death or nonfatal myocardial infarction) had occurred in 123 patients in the invasive group and in 129 patients in the conservative group (HR 1.01, 95% CI 0.79-1.29). There was also no difference in angina-related quality of life assessed by the Seattle Angina Questionnaire summary score. The invasive strategy was associated more strokes (22 versus 6 participants [HR 3.76, 95% CI 1.52-9.32]) and with more death or initiation of dialysis (75 versus 66 participants [HR 1.48, 95% CI 1.04-2.11]).

RECOMMENDATIONS OF OTHERS — We generally agree with recommendations made by the American College of Cardiology Foundation/American Heart Association and the European Society of Cardiology [27-29].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic coronary syndrome" and "Society guideline links: Percutaneous coronary intervention" and "Society guideline links: Coronary artery bypass graft surgery".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topics (see "Patient education: Cardiac catheterization (The Basics)" and "Patient education: Treatment choices for angina (chest pain) (The Basics)")

Beyond the Basics topics (see "Patient education: Medications for angina (Beyond the Basics)" and "Patient education: Angina treatment — medical versus interventional therapy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Indications for coronary artery revascularization

Patients in whom maximal medical therapy has not satisfactorily improved anginal symptoms or who are intolerant of medical therapy. (See 'Relief of angina' above.)

Patients with high-risk anatomy that has an evidence-based survival benefit, including left main or left main equivalent disease and three-vessel coronary artery disease, particularly with a reduced left ventricular ejection fraction (usually <40 percent and selected patients with intermediate-risk criteria on noninvasive testing, regardless of anginal severity). (See 'Indications' above and 'Severity of coronary artery disease' above.)

In other patients with stable angina, we pursue medical therapy and lifestyle changes rather than immediate revascularization plus medical therapy.

Other considerations

Patient preference – Some patients may prefer revascularization even if they do not have a definite indication. We favor a team-based approach and shared decision-making in these cases.

Severe coronary artery disease – Among patients with more severe coronary artery disease who do not meet criteria for revascularization with coronary artery bypass graft surgery (CABG), there is some evidence that outcomes are better with percutaneous coronary intervention (PCI) than optimal medical therapy.

Reduced left ventricular systolic function – The role of revascularization in patients with ischemic cardiomyopathy is discussed separately. (See "Treatment of ischemic cardiomyopathy".)

Patients with diabetes – While the indications for revascularization are similar for patients with and without diabetes, there is evidence to prefer CABG to PCI in those with multivessel disease. This issue is discussed separately. (See "Coronary artery revascularization in stable patients with diabetes mellitus", section on 'PCI versus CABG'.)

Advanced chronic kidney disease – Coronary artery revascularization for stable angina in patients with advanced chronic kidney disease (CKD) may not lead to reduction in cardiac events or angina symptoms. (See 'Advanced chronic kidney disease' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Julian M. Aroesty for his contributions as an author to prior versions of this topic review.

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