Non-ST-elevation acute coronary syndromes: Selecting an approach to revascularization

INTRODUCTION — Patients with non-ST-elevation acute coronary syndrome (NSTEACS, which includes the presentations of non-ST-elevation myocardial infarction [NSTEMI] and unstable angina) due to suspected coronary artery occlusion (ie, Type I myocardial infarction [MI]) typically undergo either invasive coronary angiography without prior noninvasive imaging (ie, invasive strategy) or stress or anatomic imaging followed by invasive coronary angiography as indicated (ie, selective angiography, conservative management).

This topic reviews the indications of each strategy.

The diagnostic evaluation of NSTEACS and the general management of these patients are presented elsewhere. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

EVALUATION — In patients with NSTEACS, the elements required to determine the approach to revascularization include:

●Cardiovascular disease history – In patients with NSTEACS, we obtain a detailed history of cardiovascular disease, cardiovascular risk factors, and any recent acute coronary syndrome or revascularization procedure (eg, coronary artery bypass grafting, percutaneous coronary intervention).

●Characterization of chest discomfort – The presenting symptoms and any ongoing symptoms should be characterized by their location, quality, timing, exacerbating factors, and ameliorating factors. In particular, the presence of any ongoing symptoms (eg, recurrence, stuttering nature), change in symptoms (eg, improvement with nitrates), or heart failure symptoms helps to determine the approach to revascularization. The details on the comprehensive evaluation of chest discomfort are described separately. (See "Evaluation of the adult with chest pain in the emergency department", section on 'History'.)

●Physical examination and vital signs – The physical examination and vital signs are used to identify the presence of cardiogenic shock and other high-risk features. (See 'Signs of ongoing myocardial dysfunction or infarction' below.)

●ECG – An electrocardiogram (ECG) is used to exclude ST-elevation MI [STEMI] and assess for signs of acute ischemia or infarction. ECG findings characteristic of NSTEMI and unstable angina are described elsewhere. (See "ECG tutorial: Myocardial ischemia and infarction" and "Electrocardiogram in the diagnosis of myocardial ischemia and infarction".)

●Laboratory tests – The essential laboratory tests include troponin, creatinine, and blood urea nitrogen levels. In all patients with suspected MI, we obtain a basic metabolic panel, leukocyte count, hemoglobin concentration, platelet count, and coagulation studies to assess the safety of angiography, anticoagulation, and antiplatelet therapies.

●Risk estimate – In patients with NSTEACS, some of our contributors use a risk calculator in combination with cardiovascular risk factors to determine the timing of revascularization. Among those who use a risk calculator, the preferred risk models are the Global Registry of Acute Coronary Events (GRACE) risk score calculator for six-month risk of death and, less commonly, the Thrombolysis in Myocardial Infarction (TIMI) risk score (calculator 1) for two-week risk of death or MI. The role of these scores in the approach to revascularization is described elsewhere in this topic. (See 'Clinically stable patients' below.)

The details on the accuracy of these scores are described separately. (See "Risk stratification after non-ST elevation acute coronary syndrome" and "Risk stratification after non-ST elevation acute coronary syndrome", section on 'Early risk stratification tools'.)

CHOICE OF REVASCULARIZATION STRATEGY

Signs of ongoing myocardial dysfunction or infarction — Patients with NSTEACS who have ongoing signs of myocardial dysfunction likely caused by infarction or who have signs or symptoms of persistent infarction or ischemia despite medical therapy require immediate angiography and appropriate revascularization. In patients who present to a center without access to percutaneous coronary intervention (PCI), it is reasonable to transfer such patients to a PCI-capable center. The signs of ongoing ischemia and infarction include:

●Hemodynamic instability or arrhythmias with or without cardiogenic shock. (See "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".)

●New onset of severe left ventricular dysfunction or overt heart failure. (See "Treatment of acute decompensated heart failure in acute coronary syndromes", section on 'Revascularization'.)

●Mechanical complications (eg, acute mitral regurgitation, ventricular septal defect). (See "Acute myocardial infarction: Mechanical complications".)

●Recurrent or persistent rest angina or ST-depression despite maximal medical therapy.

This approach is consistent with professional guidelines [1,2].

In our experience, this group of patients benefits from immediate angiography. There are few data to guide practice; patients with these features were generally excluded from large trials of patients with NSTEMI or unstable angina.

Clinically stable patients — In patients without any of the features listed above, the approach to revascularization depends on the history and other evidence of acute ischemia or infarction:

Evidence of infarction (NSTEMI) — In patients with an appropriate history and elevated troponin or ST-segment depression (ie, NSTEMI), we suggest invasive coronary angiography ("invasive strategy") rather than other management strategies (eg, stress or noninvasive imaging followed by appropriate angiography ["selective angiography" or "conservative strategy"]). However, it is reasonable to pursue imaging first in patients in whom stress (eg, nuclear perfusion, exercise echocardiography) or anatomic imaging (coronary computed tomographic angiography [CCTA]) can be performed and who either have risk factors for procedural complications (eg, bleeding, difficult arterial access, kidney dysfunction) or present to a center without access to invasive coronary angiography.

Invasive angiography with appropriate PCI is typically performed within 48 hours of presentation. However, it is reasonable to perform angiography within 24 hours in high-risk patients, including those with multiple risk factors for MI (eg, diabetes, known coronary artery disease [CAD]) or who have a GRACE score for six-month mortality >140 points.

This approach is consistent with professional guidelines [1,2].

Our rationale for the choice of revascularization strategy, timing of revascularization, and role of risk scores is as follows:

●Invasive strategy or selective angiography – Our approach to choosing between an invasive strategy and selective angiography is based on our experience as well as the results of large trials and meta-analyses. In general, trials show that an invasive strategy decreases the risk of MI but does not reduce the risk of death compared with selective angiography. However, the direct application of these results to practice is limited based on the variable definitions of ischemia (eg, symptoms only versus objective evidence), use of older troponin assays, limited use of modern antiplatelet therapies, predominant use of femoral rather than radial access, and high risk of bias. The results of these trials were summarized by a meta-analysis published in 2017:

•In a meta-analysis, patients assigned to an invasive strategy had a lower risk of acute MI (3.1 versus 4.8 percent with a conservative strategy, risk ratio [RR] 0.79, 95% CI 0.63-1.0) and refractory angina (20 versus 33 percent; RR 0.64, 95% CI 0.52-0.79) but similar rates of mortality (3.7 versus 4.2 percent; RR 0.9, 95% CI 0.76-1.08) [3]. In patients who underwent an invasive strategy, the risk of bleeding and procedure-related MI was increased.

●Timing of angiography for an invasive strategy – Trials that evaluated the timing of angiography among patients undergoing an invasive strategy generally showed similar effects between angiography within 12 to 24 hours and angiography performed prior to discharge. However, there was a broad array of time-to-angiography in these trials. In subgroup analyses of patients at high risk for adverse cardiac events, there were conflicting results on the value of coronary angiography within 24 hours:

•In the VERDICT trial, 2147 patients with NSTEACS and either ECG changes or elevated troponin were assigned to angiography within 12 hours of diagnosis ("very early" angiography group) or within 48 to 72 hours of diagnosis ("standard" angiography group) [4]. Very early and standard angiography occurred at a median of 5 and 62 hours, respectively, after randomization. At a median follow-up of 4.3 years, assignment to very early strategy was associated with a lower risk of nonfatal acute MI (8.4 versus 11.2 percent; hazard ratio [HR] 0.73, 95% CI 0.56-0.96) but not with a lower incidence of death (12.2 versus 12.6 percent) or the primary composite endpoint (27.5 versus 29.5 percent).

In a prespecified analysis of subgroups defined by their GRACE score, there was a lower risk of the primary outcome in patients with a GRACE score >140 points who were assigned to the very early angiography group (HR 0.81, 95% CI 0.67-1.01, interaction p = 0.023).

•A 2017 meta-analysis evaluated the timing of angiography and included eight randomized trials that compared an early invasive strategy with a delayed invasive strategy in 5324 patients with NSTEACS (79 percent of patients had elevated biomarkers) [5]. The trials were performed between 2000 and 2016, and the median follow-up was 180 days. Due to differences in the trials' definition of early and delayed angiography, "early" angiography included patients in whom angiography was performed within 24 hours of presentation, while "delayed" angiography included patients in whom angiography was performed between 12 to 108 hours after presentation. The rates of mortality (HR 0.81, 95% CI 0.64-1.03) and nonfatal MI (HR 0.91, 95% CI 0.57-1.46) were similar between the two groups.

In subgroup analyses, patients with elevated biomarkers, diabetes, a GRACE risk score more than 140 points, or who were 75 years of age or greater had lower point estimates of mortality with an early invasive strategy, but these effects did not reach statistical significance.

•The TIMACS trial was the largest trial to compare the timing of angiography in patients assigned to an invasive strategy [6]. In patients assigned to angiography <24 hours from randomization or to angiography at least 36 hours after randomization, the rates of death, MI, and stroke were similar at six months. In a prespecified subgroup of patients with a GRACE score ≥140 points, assignment to angiography at <24 hours after randomization was associated with a lower risk of the primary outcome (14 versus 21 percent; HR 0.65, 95% CI 0.48-0.69).

●Role of risk scores – The contributors to this topic have different approaches to routine use of risk scores. The GRACE and TIMI risk scores are accurate scores with extensive validation data, but some experts perceive the routine use of these scores to be cumbersome. In trials that evaluated the effects of the routine use of risk scores, the impact of scores on processes of care was variable, and rates of death and MI were similar to usual care:

•In a trial that included 3050 patients with NSTEACS, management with routine use of the GRACE risk score or with usual care had similar rates of adherence to guideline-recommended processes of care (77 versus 75 percent), cardiovascular death (3.3 versus 3.5 percent), nonfatal MI (6.6 versus 5.7 percent), and new-onset HF (4.2 versus 4.8 percent) [7]. Participating hospitals managed clusters of patients with usual care and then with risk model-based care (ie, stepped wedge design), which may have biased the trial result toward no effect.

•Another trial, which was stopped early due to futility, demonstrated that patients with acute coronary syndrome managed with the GRACE risk score were more likely to undergo an early invasive strategy (92 versus 84 percent; odds ratio [OR] 2.3, 95% CI 1.3-4.0), but rates of mortality and MI were similar in patients managed with or without a risk score at 12 months (9.2 versus 13.4 percent in those managed without a risk score; OR 0.66, 95% CI 0.38-1.14) [8].

No objective evidence of ischemia (unstable angina) — In patients who have a presentation suspicious for myocardial ischemia or infarction but who have normal troponin and ECG findings (ie, unstable angina), we typically observe the patient in a monitored setting and obtain additional ECGs and troponin testing (algorithm 1). After additional monitoring, one of the following typically occurs:

●Evidence of ischemia or infarction is detected – In patients in whom further testing confirms the presence of NSTEMI, we manage the patient as appropriate for NSTEMI. (See 'Evidence of infarction (NSTEMI)' above.)

●No evidence of ischemia or infarction is detected – In patients who have no signs of NSTEMI after appropriate monitoring, we use a heart pathway (algorithm 1) to determine the next steps in the diagnostic evaluation. In general, patients with indeterminate findings (eg, T-wave inversions) or significant risk factors for ischemia may undergo stress or anatomic imaging prior to discharge, while patients without clear evidence of ischemia who are at very low risk of death or MI may be managed without imaging but with rapid outpatient evaluation. The detailed approach to management of these patients is discussed separately. (See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Care pathways' and "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Noninvasive evaluation'.)

This approach agrees with European guidelines, while United States guidelines endorse invasive coronary angiography prior to discharge for low-risk patients [1,2].

Since routine angiography is not clearly associated with a mortality benefit in this group of patients, and there is no evidence of ongoing ischemia or infarction, these patients can undergo stress (eg, nuclear perfusion) or anatomic imaging (eg, CCTA) to further assess for the presence of obstructive CAD. Details on the evidence for this approach are discussed separately. (See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Care pathways'.)

Recent acute coronary syndrome or revascularization — Patients with recent NSTEACS, STEMI, PCI, or coronary artery bypass grafting who present with symptoms of acute coronary syndrome are managed on a case-by-case basis with involvement of cardiology or cardiac surgery. In such patients, we use a low threshold to obtain invasive coronary angiography.

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: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)".)

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 5^th to 6^th 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 10^th to 12^th 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.)

●Beyond the Basics topics (see "Patient education: Stenting for the heart (Beyond the Basics)" and "Patient education: Heart attack (Beyond the Basics)" and "Patient education: Coronary artery bypass graft surgery (Beyond the Basics)")

●Basics topic (see "Patient education: Coronary artery bypass graft surgery (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Evaluation – The evaluation required to choose a revascularization strategy includes (see 'Evaluation' above):

•Cardiovascular disease history and risk factors

•Vital signs and physical examination findings with a focus on identifying cardiogenic shock

•Laboratory testing (eg, troponin, creatinine, coagulation studies)

•ECG

●Choice of revascularization strategy

•Signs of ongoing myocardial dysfunction or infarction – Patients with non-ST-elevation acute coronary syndrome (NSTEACS) who have ongoing signs of myocardial dysfunction likely caused by infarction or who have signs or symptoms of persistent infarction or ischemia despite medical therapy require immediate angiography and appropriate revascularization. In patients who present to a center without access to percutaneous coronary intervention (PCI), it is reasonable to transfer such patients to a PCI-capable center. The signs of ongoing ischemia and infarction include (see 'Signs of ongoing myocardial dysfunction or infarction' above):

-Hemodynamic instability or arrhythmias with or without cardiogenic shock

-New onset of severe left ventricular dysfunction or overt heart failure

-Mechanical complications (eg, acute mitral regurgitation, ventricular septal defect)

-Recurrent or persistent rest angina or ST-segment depression despite maximal medical therapy

•Clinically stable patients – In patients without any of the features listed above, the approach to revascularization depends on the history and evidence of acute infarction (see 'Clinically stable patients' above):

-Evidence of infarction (NSTEMI) – In patients with an appropriate history and elevated troponin or ST-segment depression (ie, non-ST-elevation myocardial infarction [NSTEMI]), we suggest invasive coronary angiography (ie, "invasive strategy") rather than other management strategies (eg, stress or noninvasive imaging followed by appropriate angiography ["selective angiography" or "conservative strategy"]) (Grade 2B).

However, it is reasonable to pursue imaging first in patients in whom stress (eg, nuclear perfusion, exercise echocardiography) or anatomic imaging (coronary computed tomographic angiography [CCTA]) can be performed and in patients who have risk factors for procedural complications (eg, bleeding, difficult arterial access) or who present to a center without access to invasive coronary angiography. (See 'Evidence of infarction (NSTEMI)' above.)

Invasive angiography with appropriate PCI is typically performed within 48 hours of presentation. However, it is reasonable to perform angiography within 24 hours in patients with multiple risk factors for myocardial infarction [MI] (eg, diabetes, known coronary artery disease [CAD]) or who have a GRACE score for six-month mortality >140 points.

-No evidence of infarction or ischemia (unstable angina) – In patients who have a presentation suspicious for myocardial ischemia (eg, accelerating exertional angina) but who have normal troponin and ECG findings (ie, unstable angina), we typically observe the patient in a monitored setting and obtain additional ECGs and troponin testing (algorithm 1). (See 'No objective evidence of ischemia (unstable angina)' above.)

Following further observation and testing, patients in whom signs of infarction or ischemia are detected (ie, NSTEMI) typically undergo management appropriate for NSTEMI (see 'Evidence of infarction (NSTEMI)' above), while patients who have no signs of ischemia or infarction are managed with a heart pathway (algorithm 1). (See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Care pathways' and "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Noninvasive evaluation'.)

-Recent acute coronary syndrome or revascularization – Patients with recent NSTEACS, ST-elevation MI [STEMI], PCI, or coronary artery bypass grafting who present with symptoms of acute coronary syndrome are managed on a case-by-case basis with involvement of cardiology or cardiac surgery. In such patients, we use a low threshold to obtain invasive coronary angiography. (See 'Recent acute coronary syndrome or revascularization' above.)