Definition and Pathophysiology
Unstable angina (UA) is an acute coronary syndrome characterized by myocardial ischaemia occurring at rest or with minimal exertion, without evidence of acute cardiomyocyte injury or necrosis. It is distinguished from acute myocardial infarction (AMI), in which myocardial ischaemia is accompanied by cardiomyocyte necrosis and cardiac troponin release meeting the criteria of the universal definition of MI.
Clinically, UA is defined by one or more of the following patterns:
Angina at rest, usually prolonged for more than 20 minutes.
New-onset severe angina.
Previously established angina that has become more frequent, more prolonged, or provoked by less exertion.
Angina occurring after a recent myocardial infarction.
UA belongs to the broader spectrum of acute coronary syndromes, which may present with recent changes in symptoms or signs, with or without ECG abnormalities and with or without an elevation in cardiac troponin. The underlying pathological mechanism is not restricted to a single lesion or process. Although Type 1 MI and acute coronary syndromes are commonly related to atherothrombotic events, myocardial ischaemia may also result from other mechanisms. Differential diagnoses and alternative causes of troponin release must therefore be considered throughout assessment.
Coronary disease is most commonly related to atheromatous plaque producing progressive narrowing or obstruction of epicardial coronary arteries. Endothelial dysfunction, coronary microvascular disease and vasospasm may coexist with atherosclerosis or may be the dominant cause of ischaemia. Other mechanisms capable of obstructing coronary arteries include embolism, dissection, coronary arteritis associated with systemic vasculitis, extrinsic compression, myocardial bridging and radiation-induced coronary disease.
The distinction between UA and NSTEMI has become increasingly dependent on the use of highly sensitive cardiac troponin assays. As detection of myocardial necrosis has improved, some patients formerly classified as having UA are now diagnosed with NSTEMI. Consequently, the proportion of NSTE-ACS patients with NSTEMI has increased while the proportion with UA has declined.
Clinical Presentation and Symptoms
The clinical spectrum of ACS is broad. Patients may be asymptomatic at presentation, have persistent chest discomfort, or present with cardiac arrest, electrical or haemodynamic instability, or cardiogenic shock. UA itself is defined by a recent change in the pattern of myocardial ischaemia rather than by a particular symptom intensity alone.
The characteristic symptom is chest discomfort, but the clinical manifestations of ischaemic heart disease are heterogeneous. Anginal equivalents may include:
Midepigastric discomfort.
Dyspnoea.
Reduced exercise tolerance.
Excessive fatigue.
These non-chest-pain manifestations are reported more frequently in females, older adults and people with diabetes. Ischaemic heart disease may also present without prominent discomfort through heart failure, arrhythmias, silent myocardial ischaemia or sudden cardiac death.
Important clinical features suggesting UA include a prolonged episode at rest, newly developed severe angina, or a clear deterioration in a previously stable pattern. Angina that occurs after a recent MI is also characteristic. The duration, frequency, precipitating threshold and recent trajectory of symptoms should be documented carefully, because these features determine whether the presentation is stable or acutely unstable.
Evaluation and Physical Examination
Initial assessment should establish whether the presentation represents ACS and whether the patient is clinically unstable. Particular attention is required for evidence of:
Ongoing or recurrent chest discomfort.
Haemodynamic instability.
Electrical instability or arrhythmia.
Heart failure.
Cardiogenic shock.
Recent myocardial infarction.
Important alternative diagnoses.
Physical examination findings are not specified in the source material. However, assessment should incorporate the patient’s overall clinical condition, cardiovascular risk factors, known coronary disease, comorbidities and possible complications. The presence of heart failure, arrhythmia or other cardiovascular instability has implications for both immediate triage and subsequent management.
The differential diagnosis must remain broad. Troponin elevation may occur in conditions other than MI, including myocarditis, sepsis, takotsubo cardiomyopathy, valvular heart disease, cardiac arrhythmias and heart failure. Myocardial injury may be acute or chronic, depending on whether serial testing demonstrates a dynamic change in troponin concentrations. These diagnoses require different treatment strategies and should not be conflated with UA.
Diagnostics
Electrocardiography
Patients with suspected ACS are initially classified according to the presenting 12-lead ECG to guide early management. ECG findings, together with subsequent troponin results, are central to initial triage and risk stratification.
UA may occur without diagnostic ECG changes. ACS as a whole may present with or without changes on the 12-lead ECG. Patients with suspected vasospastic angina should undergo a resting 12-lead ECG during symptoms when possible. Repetitive rest angina accompanied by transient ST-segment changes that resolve with nitrates or calcium-channel antagonists suggests vasospasm; invasive functional angiography is recommended in that setting to confirm the diagnosis and assess the severity of underlying atherosclerotic disease.
Cardiac Biomarker Assessment
Serial cardiac troponin testing is essential to distinguish UA from NSTEMI and other forms of myocardial injury. UA requires the absence of acute cardiomyocyte injury or necrosis. By contrast, NSTEMI is defined by evidence of myocardial necrosis, generally reflected by cardiac troponin release in the clinical setting of acute myocardial ischaemia.
The interpretation of troponin should be integrated with symptoms, ECG findings and the overall clinical context. An elevated troponin does not by itself establish Type 1 MI, because myocardial injury can arise from non-ischaemic mechanisms and MI can result from several different pathophysiological types.
Imaging and Functional Assessment
The source material does not provide a detailed diagnostic algorithm for imaging in acute UA. In chronic coronary disease, non-invasive modalities used for diagnostic and prognostic evaluation include:
Exercise ECG.
Stress single-photon emission computed tomography.
Stress positron-emission tomography.
Stress echocardiography.
Stress cardiac magnetic resonance imaging.
Coronary computed tomography angiography.
For patients with persistent symptoms and suspected angina or ischaemia with non-obstructive coronary arteries, invasive coronary functional testing may identify treatable endotypes and improve symptoms and quality of life. This is particularly relevant when angiography shows normal arteries, non-obstructive disease, or intermediate stenoses with normal fractional flow reserve or instantaneous wave-free ratio.
Invasive Coronary Assessment
Coronary angiography and revascularization decisions should be based on the clinical presentation, risk profile, coronary anatomy and functional significance of lesions. Physiological assessment can alter management substantially in patients with coronary stenoses. In an ACS registry, systematic fractional-flow-reserve assessment changed the management strategy in a substantial proportion of cases, including shifts between coronary artery bypass grafting, percutaneous coronary intervention and medical treatment.
The source material does not provide a complete acute invasive-management pathway or specific timing recommendations for angiography in UA. It does, however, emphasize that ECG and troponin results guide initial triage and that later management becomes broadly similar across ACS categories after acute stabilization.
Biomarkers and Laboratory Findings
UA is defined by the absence of acute cardiomyocyte injury or necrosis. Accordingly, cardiac troponin concentrations do not demonstrate the pattern required for a diagnosis of NSTEMI or another MI.
Highly sensitive troponin assays have increased detection of myocardial necrosis and have therefore shifted classification from UA toward NSTEMI in some patients. Serial testing is important because the distinction between acute and chronic myocardial injury depends on evidence of dynamic change in troponin concentration.
The source material does not specify additional laboratory tests, thresholds, or biomarker-based risk scores for UA.
Treatment and Management
Immediate Management Principles
Management begins with rapid clinical classification and stabilization. Patients with suspected ACS should be assessed for:
Ongoing ischaemic symptoms.
ECG abnormalities.
Troponin elevation or dynamic change.
Electrical or haemodynamic instability.
Heart failure or cardiogenic shock.
Alternative causes of myocardial injury.
Although the initial ECG and troponin pattern determine early triage, subsequent management after acute treatment and stabilization is described as broadly applicable across ACS presentations. The focus of the source material is predominantly on Type 1 MI, but alternative diagnoses must be considered at every stage because their mechanisms, prognosis and treatments differ.
The source material does not provide specific doses or a complete drug regimen for acute UA. It also does not provide detailed recommendations regarding aspirin, P2Y12 inhibitors, anticoagulants, nitrates, beta-blockers or other acute ACS drugs.
Disease-Modifying Medical Therapy
Long-term management of chronic coronary disease has three principal objectives:
Relief of symptoms.
Prevention of nonfatal events such as MI.
Improvement of long-term survival.
Medical therapy is frequently effective. Disease-modifying management includes antiplatelet, lipid-lowering and anti-inflammatory therapies, together with treatment of hypertension and diabetes and interventions directed toward weight reduction when appropriate. Smoking cessation and exercise are important components of optimal medical therapy.
The risks and benefits of antithrombotic treatment should be reassessed over time, particularly the balance between ischaemic benefit and bleeding risk. Treatment should be adjusted according to comorbidities and the patient’s evolving clinical condition.
Antianginal Therapy
Antianginal treatment should be individualized according to the severity and frequency of symptoms, functional limitation, precipitating factors, comorbidities and patient goals. Management should include explanation of the condition, reassurance, treatment of aggravating conditions, adaptation of activity where needed, risk-factor modification and consideration of revascularization.
The source material does not specify doses for antianginal drugs. In patients with angina or ischaemia and non-obstructive coronary arteries, ranolazine is described as an antianginal option that may improve myocyte relaxation and ventricular compliance by reducing sodium and calcium overload. For isolated vasospastic angina, calcium-channel blockers are recommended to control symptoms and prevent ischaemia and potentially fatal complications.
Revascularization
Revascularization should not be regarded as an automatic substitute for medical treatment. In stable coronary disease, an initial conservative strategy is generally preferred for patients with moderate or severe inducible ischaemia who have no left main disease and no LVEF below 35%, once optimal medical therapy has been established. Nevertheless, revascularization may provide greater freedom from angina and better angina-related health status, particularly in patients with persistent symptoms despite medical therapy.
The evidence summarized in the source material indicates that routine revascularization has not consistently improved overall survival compared with medical therapy alone in chronic coronary disease. Revascularization does, however, reduce spontaneous MI, unstable angina and anginal symptoms in selected populations, while introducing a risk of procedural MI.
Coronary artery bypass grafting has a survival advantage over medical therapy alone in patients with left main disease and in patients with coronary disease and LV dysfunction, particularly when LVEF is ≤35%. CABG also has a later mortality benefit compared with PCI in patients with three-vessel disease and extensive anatomical complexity or in patients with diabetes and significant multivessel disease. These benefits must be balanced against a higher early periprocedural stroke risk and longer in-hospital recovery.
For patients with left main or multivessel disease, decisions should involve a cardiac surgeon, interventional cardiologist and referring cardiologist. PCI, CABG and optimal medical therapy should be discussed together with the patient and family, incorporating patient preferences.
Following PCI, optimal medical therapy remains necessary, including management of hypertension and diabetes, exercise, smoking cessation and lipid management, particularly statin therapy.
Recurrent and Refractory Angina
Refractory angina is defined as symptoms lasting more than three months that result from established reversible ischaemia and remain uncontrolled despite escalation of antianginal therapy and, where appropriate, PCI or CABG. It may occur with obstructive CAD that is no longer amenable to further revascularization, including recanalization of chronic total occlusion, or in the setting of ANOCA/INOCA after the relevant endotype has been investigated.
Patients with refractory angina commonly have poor quality of life and frequent hospitalizations. After conventional anti-ischaemic treatment and mechanical revascularization options have been exhausted, enhanced external counterpulsation and the coronary sinus reducer are identified as the most promising and readily implementable options among currently available therapies.
Spinal cord stimulation may be considered after medical treatment has failed. Angiogenic therapies involving vascular endothelial growth factors or fibroblast growth factors, and stem-cell therapy using intramyocardial delivery of CD34+ cells, remain investigational; larger sham-controlled randomized trials are needed to define their role.
Guideline Recommendations
The source material supports the following recommendations:
Suspected ACS should be assessed with clinical evaluation, a 12-lead ECG and cardiac troponin testing.
ECG findings and troponin elevation are important for initial triage, diagnosis and risk stratification.
UA should be distinguished from NSTEMI by the absence of acute cardiomyocyte injury or necrosis.
Alternative causes of troponin elevation and myocardial injury should be considered throughout assessment.
In suspected vasospastic angina, a resting 12-lead ECG during angina is recommended.
In suspected vasospastic angina with recurrent rest episodes and transient ST-segment changes resolving with nitrates or calcium antagonists, invasive functional angiography is recommended.
Calcium-channel blockers are recommended for isolated vasospastic angina.
Persistently symptomatic patients with suspected ANOCA/INOCA, poor quality of life and non-obstructive or physiologically non-significant coronary disease should undergo invasive coronary functional testing to identify treatable endotypes, taking patient preferences into account.
Chronic coronary disease management should be patient-centred and team-based, addressing symptoms, risk factors, adverse clinical outcomes and social determinants of health.
Revascularization decisions should incorporate coronary anatomy, LV function, comorbidities, procedural risks and patient preferences.
Patients with left main or complex multivessel disease should receive multidisciplinary consultation regarding PCI, CABG and medical therapy.
Optimal medical therapy should continue after PCI.
Prognosis and Follow-up
UA indicates an acute change in the pattern of myocardial ischaemia and therefore requires careful risk assessment. Its contemporary prognosis is influenced by the underlying coronary anatomy, LV function, comorbidities, arrhythmias and the subsequent development of MI or heart failure.
In chronic coronary disease, contemporary treatment has improved outcomes compared with historical cohorts. The reported annual mortality is approximately 1%–3%, with an annual rate of major ischaemic events of approximately 1%–2%. Poor exercise capacity and LV dysfunction are associated with worse outcomes.
Long-term follow-up should assess:
Recurrence or progression of angina.
Cardiovascular risk factors.
Residual symptoms and functional limitation.
LV remodelling or dysfunction after MI.
Functional mitral regurgitation.
Heart failure.
Significant arrhythmias.
Peripheral arterial disease and stroke.
Renal dysfunction and other non-cardiac comorbidities.
Adherence to and tolerance of antiplatelet, lipid-lowering, antianginal and other disease-modifying therapy.
The continuing balance between antithrombotic benefit and bleeding risk.
The principal objectives of follow-up are to identify symptoms suggesting progression of CAD, refine risk stratification and detect extracoronary or cardiac complications promptly. Medication should be optimized as comorbidities and clinical status evolve.
Angina may resolve spontaneously in a substantial proportion of patients with chronic coronary syndromes, often without revascularization or changes in antianginal therapy. Persistent or recurrent angina is associated with higher cardiovascular risk, particularly in patients with a previous MI. Consequently, symptom assessment remains important, but it should be integrated with objective evaluation of LV function, rhythm, heart failure and overall coronary risk rather than used in isolation.
