Dr Chris Arden explains why new guidance on the management of symptomatic stable angina in primary care will ensure that more patients are treated correctly


  • This working party guideline was developed during a 1-day meeting
  • The development of this guidance was supported by a grant from Servier Laboratories Ltd
  • The content of the working party guideline and this article is independent of and not influenced by the commercial sponsorship

It is estimated that approximately 2 million individuals—4.8% of men and 3.4% of women—have a diagnosis of angina, with an incidence rate of 0.2% (338,000 new cases) per year.1,2 Angina has a significant negative effect on quality of life, including physical activity, emotional well being, and personal and sexual relationships.3 Not only does angina pose a considerable burden on patients and carers, it also places a significant demand on NHS resources; each year there are:4

  • 2.4 million GP consultations
  • 254,000 outpatient referrals
  • 117,000 coronary angiograms
  • 214,000 coronary bypass operations
  • 17,700 percutaneous coronary interventions.

The approximate net financial cost to the NHS of investigating and managing patients with angina is £700 million each year.4

The overall prognosis for patients with coronary heart disease (CHD), including angina, has improved significantly over the past three decades, due primarily to the improved management of acute coronary events and risk factors, including secondary prevention. Pharmacological therapies have had a positive impact on overall prognosis, including treatment with:

  • antiplatelet agents
  • lipid modification therapy (statins)
  • angiotensin-converting enzyme (ACE) inhibitors
  • beta blockers.

In a British Cardiac Patients Association (2007) survey:5

  • 45% of all respondents described their angina symptoms as extremely or moderately debilitating
  • over one-third (35%) reported that angina has a significant impact on their overall quality of life
  • limitations on day-to-day activities, employment prospects, and future health status were listed as major health concerns.

Research suggests that many patients with angina are not currently receiving optimal medical therapy, which often results in them experiencing frequent, debilitating, and limiting symptoms. These symptoms may lead to inappropriate early referral for revascularisation. The increasing number of pharmacological treatment options available can be a potential challenge for GPs who try to ensure that patients receive appropriate and optimal therapy. With this in mind, and in the absence of current clinical guidelines, a working party of GPs and cardiologists has developed a guideline entitled ‘Consensus guideline for the management of symptomatic stable angina in primary care’.6 This guidance has been written to assist prescribers and those managing individuals with CHD to ensure their patients receive appropriate optimisation of their medical therapy, with the aim of improving symptom control, quality of life, and prognosis.

Classification

Stable angina is typically characterised by aching or discomfort in the chest, jaw, shoulders, arms, or back, is usually elicited by exertion or emotional stress, and is relieved by rest or sublingual glyceryl trinitrate.6

Unstable angina is normally seen at rest and is prolonged (lasting >20 minutes); the pain progressively increases in frequency and intensity, and is severe enough to limit activity.6 The guidance described below concentrates only on stable angina.

Assessment of stable angina

History
In order to ensure an accurate diagnosis it is vital to take a thorough history. Important features to ask about are:6

  • nature, frequency, intensity, and stability of symptoms
  • precipitating factors or triggers
  • cardiovascular risk factors, including smoking, hypertension, diabetes, dyslipidaemia, exercise/lifestyle factors, and family history of premature cardiovascular disease
  • history of co-morbid conditions, particularly cerebrovascular, peripheral vascular, and reno-vascular disease
  • illicit drug use, especially in the young
  • current medications, including adherence to prescribed regimen
  • exercise habit.

Examination
Physical examination is important to exclude other conditions that may be associated with, or exacerbate, angina including aortic stenosis, other significant valvular disease, or hypertrophic cardiomyopathy. It is also important to assess the overall cardiovascular status of the patient, in particular looking for any signs of cerebrovascular or peripheral vascular disease. In many patients, physical examination may be normal.6

Investigations
The aim of investigations is to exclude other co-morbid conditions that may precipitate or aggravate underlying CHD. They also provide additional information that is helpful when assessing an individual’s overall risk and prognosis. Such investigations include:6

  • blood tests:
    • haemoglobin to identify underlying anaemia
    • full lipid profile
    • random blood glucose to identify previously undiagnosed diabetes
    • renal and liver function tests
  • resting 12-lead electrocardiogram (ECG) for:
    • rhythm
    • rate
    • evidence of pre-existing structural heart disease, including left bundle branch block (LBBB), left ventricular hypertrophy (LVH), or previous myocardial infarction
    • ST changes.

A normal ECG does not exclude the possibility that the angina is due to underlying CHD.6

Referral and risk stratification
All patients with suspected angina should be referred for investigation. The role of referral is to confirm or exclude the diagnosis of angina; identify those patients who require angiography, with a view to possible revascularisation, if this is indicated, to improve their prognosis; determine a personalised management plan, incorporating medical therapy and/or intervention; and arrange appropriate cardiac rehabilitation.

Typical investigations that may be performed in secondary care include:

  • a functional assessment, including either stress echocardiography, myocardial perfusion imaging, or a stress cardiac magnetic resonance imaging scan
  • anatomical assessment, including angiography or coronary computed tomography imaging
  • an exercise ECG
  • echocardiography, especially if structural or valvular abnormalities are suspected.

Before any individual is referred to secondary care for assessment it is important to give lifestyle advice, especially in relation to smoking, exercise, and alcohol intake. Management of risk factors, including hypertension, diabetes, and dyslipidaemia should be optimised. This is also an opportune time to discuss the indications, and benefits, of potential drug treatment, as well as the need for referral and how best to manage their symptoms.6

Initial therapy

Initial drug therapy should include the following:6

  • aspirin 75 mg/day (or clopidogrel 75 mg/day if there is a true intolerance)
  • consideration of sublingual glyceryl trinitrate (GTN) spray or tablets
  • beta blockade (e.g. bisoprolol
    2.5–5 mg/day, atenolol 25–50 mg/day, or metoprolol 50–100 mg/day).

If beta blockers are contraindicated, or there is a known intolerance, alternative rate-lowering agents should be considered, such as ivabradine 5–7.5 mg twice a day or diltiazem modified release 180 mg/day.6

Further advice should be given to encourage the strict management of other co-existing risk factors for CHD and of concomitant disorders including hypertension and diabetes:6

  • Smoking—advice and support to stop (e.g. counselling, pharmacotherapy)
  • Hypertension—all patients with angina should have their blood pressure (BP) actively managed, in accordance with the British Hypertension Society (BHS) guideline, aiming for an optimal BP <140/90 mmHg7
  • Diet—modify diet in line with healthy eating advice
  • Weight—encourage weight loss towards a body mass index (BMI) <25 kg/m2
  • Exercise—encourage light to moderate exercise
  • Lipids—all patients with angina should have their baseline fasting lipid profile measured, and actively managed to aim for a total cholesterol <4.0 mmol/l and low-density lipoprotein (LDL) cholesterol <2.0 mmol/l8
  • Alcohol intake—encourage <3 units/day for men and <2 units/day for women9
  • Diabetes mellitus—aim to achieve HbA1c <7%.

Management following confirmed diagnosis

Once the diagnosis of angina is confirmed, a pharmacological approach to symptom control should be taken in those patients who are not deemed to be at high risk of acute coronary events, or who have other compelling indications (e.g. aortic stenosis) for urgent revascularisation or surgery.

Pharmacological treatment
The aims of pharmacological treatment are to control the patient’s symptoms and improve their prognosis, give lifestyle support, and risk reduction.6 The patient’s preferences should be taken into account when selecting appropriate medication, together with any pre-existing renal or hepatic impairment and potential drug interactions.6

Every patient with confirmed angina should have their drug therapy optimised, and dosing of one drug should be titrated to maximum tolerated dose before consideration is given to switching to an alternative agent. It is also advisable to switch drug combinations before attempting a three-drug regimen for the treatment of symptoms. Revascularisation may be considered for patients with suitable anatomy who do not respond adequately to medical therapy.6

Symptomatic control
Heart rate control is the first and most important step in order to achieve symptomatic control in patients with stable angina. A target heart rate is 55–60 beats per minute (bpm),10 and drug therapy should be titrated against symptoms and heart rate (see Figure 1).6

In patients who are able to tolerate beta blockers, these agents should be titrated to the maximum tolerated dose, aiming for a heart rate of <60 bpm. If they remain symptomatic and the heart rate is <60 bpm, then the addition of nicorandil, a dihydropyridine calcium antagonist, long-acting nitrate, or ranolazine should be considered.6

If the heart rate remains >60 bpm on an optimal tolerated beta-blocker dose, then ivabradine 5–7.5 mg twice a day should be added. Further anti-anginal therapy may then be considered if the patient remains symptomatic.6

Patients with stable angina who have a resting heart rate of >60 bpm and BP <140/90 mmHg, who are either intolerant of beta blockers or in whom these are contraindicated, should be commenced on ivabradine 5–7.5 mg twice a day (or diltiazem modified-release 180 mg once a day if the BP >140/90 mmHg).6 Ivabradine should also be considered in those patients already on dihydropyridine calcium antagonists and who are hypertensive (BP >140/90 mmHg) with a resting heart rate >60 bpm.6

Additional anti-anginal medication may be added as required for symptomatic control depending on the patient’s heart rate, blood pressure, and symptoms. The use of beta blockers or ivabradine in combination with diltiazem is not recommended due to interactions.11

Figure 1: Symptomatic algorithm to show how controlling heart rate can achieve symptom control6
angina NB The use of beta-blockers or ivabradine in combination with diltiazem is not recommended due to interactions (BNF September 2010).

Prognostic therapy

To improve prognosis, the following medications should be mandatory therapy for secondary prevention in all patients with stable angina:6

  • antithrombotic therapy:
    • aspirin 75 mg/day
    • if aspirin hypersensitivity or true intolerance, use clopidogrel
      75 mg/day
  • lipid modification therapy:
    • initial therapy simvastatin 40 mg once a day
    • target total cholesterol <4.0 mmol/l and/or LDL cholesterol <2.0 mmol/l
    • switch to alternative statin if target not reached
    • if true statin intolerance use an alternative lipid lowering therapy (e.g. ezetimibe 10 mg once a day or bezafibrate 400 mg once a day)
  • ACE inhibitors; all patients with angina, not only those with a co-existing indication, should be treated with an ACE inhibitor,12 either:6
    • ramipril 2.5 mg once a day, ideally titrating to 10 mg taken at night
      or
    • perindopril 4 mg once a day, titrating to 8 mg once a day.

Beta blockers are indicated for long-term maintenance therapy (up to 2 years) in patients who have had a previous myocardial infarction: either bisoprolol 2.5–10 mg once a day or metoprolol 50–200 mg once a day.6

Patients who are established on optimal maintenance therapy and who are asymptomatic should be reviewed regularly so that lifestyle advice can be reinforced and risk factors can be actively managed. Adherence to prescribed drug therapy should also be checked, in order to improve the long-term prognosis (see Box 1).6

Those patients with stable angina who remain symptomatic on optimal tolerated medical therapy should be referred for further assessment and considered for revascularisation.6

Box 1: Checklist for the ongoing management of stable angina patients6

Visit 1

  • Start patient on:
    • beta blocker
    • aspirin
    • glyceryl trinitrate

Visit 2 (diagnosis confirmed)

  • Reinforce lifestyle advice
  • Review:
    • heart rate control (target 55–60 bpm)
    • risk factor management (statin, ACE inhibitor)
  • Enroll patients on structured cardiac rehabilitation programme
  • Address psychosocial interventions—one way is to use the ‘Angina Plan’ (www.anginaplan.org.uk)

Visit 3

  • Review ongoing heart rate control
  • Add other anti-anginals as necessary to optimise symptom control

ACE=angiotensin-converting enzyme; bpm=beats per minute

Summary

Although there has been a steady increase in the prevalence of angina over the past two decades, there has also been a significant improvement in morbidity and mortality associated with the condition. This has been achieved through improvements in management of acute coronary events, as well as better secondary prevention and modification of cardiovascular risk factors. The majority of patients will benefit, both in terms of prognosis, as well as symptom control, if their lifestyle and pharmacotherapy can be optimised. The challenge for primary care is to ensure that patients receive appropriate advice and support, together with optimisation of their medical therapy, to ensure continuing improvements in quality of life, prognosis, and long-term outcomes.

Members of the working party guideline

  • Kim Fox, Professor of Clinical Cardiology, Royal Brompton Hospital, London
  • Chris Arden, GPwSI Cardiology, Southampton and PCCS Board Member
  • Alan Begg, GP, Montrose, Scotland, and PCCS Member
  • Ahmet Fuat, GPwSI Cardiology, Darlington, PCCS Honorary Secretary, and Senior Clinical Lecturer, Durham University
  • Alistair S. Hall, Professor of Clinical Cardiology, Leeds Teaching Hospitals Trusts
  • Charles Knight, Consultant Cardiologist, Barts and the London NHS Trust.
  1. Janes M, Rait G, Falconer J, Feder G. Systematic review: prognosis of angina in primary care. Family Practice 2006; 23 (5): 520–528.
  2. Department of Health—Coronary heart disease. www.dh.gov.uk (accessed 20 September 2010).
  3. Izzat L, Knight E. New data highlight burden of sub-optimal management of angina. Br J Cardiol 2008; 15 (4): 191–194.
  4. Stewart S, Murphy N, Walker A et al. The current cost of angina pectoris to the National Health Service in the UK. Heart 2003; 89 (8): 848–853.
  5. The British Cardiac Patients Association. Angina awareness survey 2007. BCPA, Servier Laboratories, 2007.
  6. Fox K, Arden C, Begg A et al. Consensus guideline for the management of symptomatic stable angina in primary care. Berkhamsted: MGP Ltd, 2010.
  7. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV):
    Summary. BMJ 2004; 328: 634–640. Available at: www.bhsoc.org pdfs/Summary%20Guidelines%202004.pdf.
  8. British Cardiac Society, British Hypertension Society, Diabetes UK et al. JBS2: Joint British societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (5): v1–v52.
  9. National Institute for Health and Care Excellence. Alcohol-use disorders: preventing the development of hazardous and harmful drinking. Public Health Guidance 24. London: NICE, 2010. Available at: www.nice.org.uk/guidance/PH24
  10. Gibbons R, Antman E, Alpert J et al. ACC/AHA 2002 guidelines update for the management of patients with chronic stable angina. J Am Coll Cardiol 2003; 41: 159–168.
  11. British National Formulary. BNF 60—September 2010. London: BMJ Group, Pharmaceutical Press, 2010.
  12. Dagenais G, Pogue J, Fox K et al. Angiotensin-converting enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet 2006; 368 (9535): 581–588.G