The prevalence of angina is increasing, with approximately two million people in the UK being diagnosed with the condition, affecting 14% of men and 8% of women. There are estimated to be 96,000 new cases each year.1
Angina is increasingly common due in part to an ageing population, being more prevalent in those aged over 55 years old and in males. Other risk factors include diabetes, hypertension, dyslipidaemia, obesity, ethnicity and adverse lifestyle factors, in particular smoking and lack of regular exercise. Angina has a significant impact on quality of life, particularly as symptoms worsen, limiting daily activities and functional status.2
Symptoms of angina may be stable, occurring predictably with physical activity, emotional stress, exposure to cold or after a heavy meal. In contrast, unstable angina, although less common, does not follow a regular pattern and often occurs at rest or with minimal provocation. Unstable angina is associated with a worse prognosis, is usually a progression from stable angina and is an indication as to the extent and severity of the underlying coronary artery disease.
The Canadian Cardiovascular Society classification is useful in assessing the severity of angina, as determined by the intensity of activity that precipitates symptoms, and hence an indication as to the impact the condition is likely to be having on an individual’s quality of life.
Long-term prognosis for those with stable angina is variable, with mortality rates varying between 0.9% –6.5% per year. An individual’s risk is determined by their baseline clinical characteristics, together with the extent of myocardial ischaemia and cardiac systolic function. The variable prognosis illustrates the importance of careful risk stratification at the time of initial diagnosis, in order to guide the intensity of treatment, whether medical, interventional or a combination of both, with the objective ultimately of improving both symptoms and mortality.

 

Functional assessment and risk stratification
The most important factors required to assess an individual’s future cardiovascular risk, and hence prognosis, most accurately are:
• Clinical evaluation (including history, examination, ECG, lifestyle factors, smoking, diabetes, metabolic syndrome, hypertension, dyslipidaemia and family history)
• Response to stress testing
• Quantification of LV function (impaired LV systolic function is the strongest predictor of a poor prognosis; resting LV ejection fraction <35% is associated with an annual mortality > 3% per year)
• Extent of coronary artery disease.3
Non-invasive functional assessment, including stress echocardiography, myocardial perfusion imaging or exercise ECG is useful in identifying those individuals who may have high-risk coronary anatomy and are likely to benefit from revascularisation. The role of the exercise ECG is increasingly reserved for assessing functional capacity in those with established coronary artery disease, rather than in the initial diagnosis, due to the test’s relatively poor specificity and sensitivity as compared with other functional imaging tests.


Management
The aims of treatment in angina are to minimise symptoms and improve quality of life, whilst also ensuring the timely institution of medical therapy or revascularisation to improve prognosis, by preventing myocardial infarction or death. Both of these approaches are complimented by the promotion of positive lifestyle measures, including smoking cessation, together with adoption of a healthy Mediterranean style diet and regular activity within the individual’s limitations. There is no evidence that vitamin or fish oil supplements confer benefit in stable angina.
The optimal management of comorbidities, including hypertension, diabetes and renovascular disease is important in modifying the atherosclerotic disease process and improving outcomes.


Pharmacological therapy to improve prognosis
Pharmacotherapy is recommended as secondary prevention for all those with angina and associated coronary artery disease. These treatments have been demonstrated to improve prognosis and reduce the risk of future vascular events, including non-fatal myocardial infarction (MI).4
• Aspirin 75mg daily (or clopidogrel 75mg daily in those intolerant of aspirin), taking into account the risk of bleeding or comorbidities. Due to the heterogeneity of those with angina, especially in the elderly, there is a relatively low risk cohort in whom the bleeding risk may outweigh any potential gain in terms of reducing cardiovascular risk
• Statin treatment should be offered to all those with angina, in line with current lipid modification guidelines and targets
• Angiotensin-converting enzyme (ACE) inhibitors should be considered for those with angina and diabetes. The evidence suggests potential benefit in this subgroup of patients. It is also recognised there are other compelling indications for ACE inhibitors in those with left ventricular systolic dysfunction, post-myocardial infarction and with concomitant renovascular disease.


Treatment of symptoms
Minimising, or ideally eradicating, symptoms in angina is a key objective and, for the majority of patients, results in an improvement in quality of life and exercise tolerance. The individual’s symptom burden and response to medical therapy also has a significant bearing on the need for further investigation or revascularisation.
Recent guidelines have defined optimal medical treatment (OMT) as the use of up to two anti-anginal drugs plus secondary prevention measures.
Consideration to adding a third anti-anginal drug should only be given when:
• The person’s symptoms are not controlled with two anti-anginal drugs and
• The person is either waiting for revascularisation or revascularisation is not considered appropriate or acceptable.4
Short acting nitrates
Symptoms of angina can effectively be relieved by the use of short acting nitrates, including glyceryl trinitrate as either a sublingual tablet or spray and should be prescribed in all those with angina. The individual should be carefully instructed in its use and also of the potential benefit of using it before any planned exercise or activity (situational prophylaxis).


First line treatment
Beta blockers or rate limiting calcium channel blockers (diltiazem or verapamil) are recommended as initial therapy with the objective of improving symptoms. These are effective in reducing myocardial oxygen consumption, as a result of lowering heart rate, myocardial contractility and blood pressure, together with increasing coronary blood flow and myocardial oxygen supply during diastole.4
The decision as to whether to opt for a beta blocker or calcium channel blocker should be based on an individual’s comorbidities, contraindications and preference. If either therapy is poorly tolerated then consideration should be given to switching to the other. If symptoms are not satisfactorily controlled with either option as monotherapy, then the guidelines recommend using a combination of a beta blocker and a calcium channel blocker, although in this situation the latter should be a dihydropyridine calcium channel blocker (amlodipine, felodipine or slow-release nifedipine).4  


Second line treatment
For those individuals with persisting symptoms, despite optimisation of beta blocker and/or calcium channel blocker doses, consideration should be given to introducing additional anti-anginal therapy. In a very few patients, i.e. those intolerant of both beta blockers and calcium channel blockers, the following may also be considered as initial monotherapy:4
• Long-acting nitrates
• Ivabradine
• Nicorandil
• Ranolazine.
The decision as to which drug is chosen should be based on the patient’s comorbidities, contraindications and preferences. Concomitant medications and comorbidities are a particular consideration in elderly patients, in order to ensure an appropriate balance is achieved between competing benefits, risks and potential side-effects of medical therapy.
Long-acting nitrates reduce the severity and frequency of angina attacks and may increase exercise tolerance, although have not been demonstrated to confer any prognostic benefit.
Ivabradine acts by inhibition of the sinus node, reducing heart rate and myocardial oxygen demand during rest and exercise. This improves symptom control and can be used in combination with either a beta blocker or dihydropyridine calcium channel blocker.
Nicorandil has a dual mechanism of action, as a potassium channel activator as well as including a nitrate moiety that dilates epicardial coronary arteries, improving myocardial perfusion. Trial data have demonstrated a reduction in hospital admissions for cardiac related chest pain.4
Ranolazine is a metabolically acting agent, which is believed to selectively inhibit sodium channels, with minimal reductions in heart rate or blood pressure.
All anti-anginal therapies should be titrated, depending on the patient’s symptoms, to their optimal tolerated doses before consideration is given to adding additional therapy.
When counselling patients with regards to the relative merits of medical treatment, it is helpful to advise them that the aim of anti-anginal treatment is to prevent episodes of angina, improve symptoms and hence quality of life, while the aim of secondary prevention is to prevent cardiovascular events, including myocardial infarction and stroke.


Medical therapy versus revascularisation
The two conventional approaches to revascularisation in coronary artery disease are either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
Although there is extensive trial data in relation to the role of PCI or CABG in the management of coronary artery disease, there is still on-going debate regarding the indications for, and optimal timing of, invasive investigation and revascularisation in stable angina.5,6
There is however robust and good evidence supporting a strategy for early invasive investigation and intervention in those patients presenting with unstable symptoms and acute coronary syndromes, in whom this approach is associated with improved outcomes. Similarly, in those patients with defined high risk coronary anatomy, including left main stem or proximal three-vessel disease, revascularisation improves symptoms and prognosis.
In acute presentations the evidence supports this approach in all patients, irrespective of age, although comorbidities, together with patient preference, must be taken into account when weighing up the relative merits of an invasive strategy, as compared with continuing medical therapy alone.
Those patients who remain symptomatic on optimal tolerated medical therapy should be considered for revascularisation and, in order to decide which procedure (PCI or CABG) may be appropriate, invasive investigations (angiography) should be offered. A proportion of these patients may still require stress imaging (echocardiography, magnetic resonance or nuclear perfusion scanning) to determine the functional significance of lesions noted on angiography and this evidence will assist in guiding management decisions as to the preferred interventional strategy.
In patients with stable angina, both PCI and CABG have proven efficacy in improving symptoms although, on available evidence, PCI does not appear to provide substantial survival benefit. CABG has been shown to improve prognosis in a subset of patients, including those who:
• Have anatomically complex three-vessel disease, with or without involvement of the left main stem
• Have diabetes mellitus
• Are aged over 65 years.
If the patient’s coronary anatomy is considered suitable for either procedure then it is recommended that PCI should be offered in preference. This is an important consideration especially in the elderly who often have other significant comorbidities and may be more susceptible to potential risks associated with anaesthesia or thoracotomy together with the prolonged post-operative recovery and convalescence associated with bypass surgery.


Cardiac rehabilitation
There is good evidence, in patients of any age, that cardiac rehabilitation programmes are helpful in improving functional performance and quality of life, together with improving adherence to treatment recommendations and the adoption of positive lifestyle measures. The evidence of benefit is particularly robust in patients seen post-MI/ACS and following revascularisation.
In those patients with stable angina the guidelines support a more tailored approach to cardiac rehabilitation, addressing the individual’s particular needs and management of residual risk factors.
The Angina Plan provides a well-resourced and structured support programme for both individuals with angina, as well as their carers, which appears to be particularly beneficial.7  

 

Conclusion
The increasing prevalence of angina, due in significant part to an ageing population and improved survival of those presenting with acute coronary events, together with increasing incidence of conditions predisposing to the development of coronary atherosclerosis, including diabetes, hypertension and renovascular disease, presents clinicians with significant challenges in ensuring patients receive timely investigation and treatment, including revascularisation if appropriate.
The prognosis for the majority with stable angina is good, although it is important to identify those patients who have adverse risk factors, with high risk coronary anatomy and poor prognosis, who would benefit from more intensive investigation and treatment, including revascularisation.
There are a wide range of effective treatment options for those with angina of all ages, which have been proven to improve symptoms, together with quality of life and prognosis. Recent guidance has been helpful in defining the optimal timing of investigation as well as the benefits of treatment and revascularisation in selected patients. It is important we employ these strategies effectively, on behalf of our patients, to ensure we improve their quality of life and prognosis.

Conflict of interest: none declared

References
1. National Institute for Health and Clinical Excellence. NICE CG 126. Management of Stable Angina (2011). www.nice.org.uk/guidance/CG126
2. British Heart Foundation. www.bhf.org.uk/statistics
3. Campeau Lucien. Grading of angina pectoris. Circulation 1976; 54: 5223 http://www.ccs.ca/download/position_statements/Grading%20of%20Angina.pdf
4. Henderson RA, O’Flynn N, Guideline Development Group Heart 2012;98: 500-7
5. Boden WE, O’Rourke RA, Teo KK et al. N Engl J Med 2007;356: 1503-16.
6. Kappetein AP, Feldman TE, Mack MJ et al. Eur Heart J 2011; 32: 2125-34.
7. The Angina Plan. www.anginaplan.org.uk