Dr Alan Begg assesses the status of the stable angina guideline from SIGN one year on and discusses its continued relevance for GPs in light of more recent studies

The guideline published by the Scottish Intercollegiate Guidelines Network (SIGN) in February 2007 remains the only current national clinical guideline on the management of stable angina.1 Just over a year after publication the recommendations have not only stood the test of time, but have been reinforced by evidence published in the past year.

The guideline deals with all aspects of angina, its assessment and the steps to establish a diagnosis, and it covers in detail the medical management both to alleviate the symptoms and to prevent future vascular events. There are also recommendations on when to consider interventional revascularisation and cardiac surgery, along with details on the benefits of each procedure. The evidence statements and recommendations within the guideline follow the standard SIGN methodology (see Figure 1).

Importantly, psychological factors are covered and the evidence underpinning the benefits of long-term structured follow-up has been examined in detail. The SIGN guideline is unique among angina guidelines in that it also covers the medical management of patients with stable coronary disease who are undergoing non-cardiac surgery, although this is not directly relevant to general practice.

Figure 1: Key to evidence statements and grades of recommendations

 
Levels of Evidence
1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias.
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias.
2++ High quality systematic reviews of case control or cohort studies.
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal.
2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal.
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal.
3 Non-analytic studies, e.g. case reports, case series.
4 Expert opinion.
 
Grades of Recommendation
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.
A At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population; or
  A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results.
B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
  Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
  Extrapolated evidence from studies rated as 2++.
D Evidence level 3 or 4; or
  Extrapolated evidence from studies rated as 2+.
Good practice points
? Recommended best practice based on the clinical experience of the guideline development group.
RCT=randomised controlled trials
This material was reproduced with kind permission of the Scottish Intercollegiate Guidelines Network

What is angina?

The term ‘angina’ is used to describe the symptom of chest pain or pressure in the chest precipitated by exercise or emotion, resulting in increased myocardial oxygen demand.1 Typical characteristics of stable angina are listed in Table 1. Not all patients will present with characteristics of exertional pain relieved by rest, so other initial presenting symptoms such as breathlessness, heaviness, or burping need to be considered.

Table 1: Typical characteristics of stable angina

Type of discomfort Tight, dull, or heavy
Location Retrosternal or left side of chest. Can radiate to left arm, neck, jaw, and back
Relation to exertion Brought on by exertion or emotional stress, and eased by rest
Duration Can last for up to several minutes after exertion or emotional stress has stopped
Associated factors Can be precipitated by cold weather or following a meal
This material was reproduced with kind permission of the Scottish Intercollegiate Guidelines Network

Initial assessment

The initial clinical history taking and assessment carried out by the GP is an important step in confirming the presence of underlying atherosclerotic coronary heart disease (CHD). It should include:

  • checking the heart rhythm
  • measuring blood pressure
  • noting the presence or absence of cardiac murmurs
  • measuring body mass index.

Laboratory investigations should be carried out to assess:

  • haemoglobin level
  • thyroid stimulating hormone
  • renal function
  • lipid profile
  • blood glucose level.

The severity of angina can be classified according to the Canadian Cardiovascular Society Classification, which can be found in the guideline.1 The SIGN guideline does not recommend using a scoring system to assess angina symptoms, on the basis that although they may be accurate in the cohort of patients from whom they are developed, this may not be the case when applied to the general population. The measurement of B-type natriuretic peptide (BNP) level is a test that in the future may be included to rule out whether or not chest pain is cardiac in origin. In one recently published study, patients presenting at a rapid access chest pain clinic (RACPC) with a BNP level of ?20 pg/ml were significantly less likely to be diagnosed with cardiac pain.2

Relevance of the guideline for primary care

The main recommendations in the guideline from SIGN on the Management of stable angina are in line with the clinical indicators in the GMS contract relevant to stable angina (see Table 2),3 and support the work of GPs with these patients (see Table 3). The published Read codes in use as part of the QOF process allow the GP to record not only individual signs, symptoms, and diagnosis, but all the procedures, processes, and investigations required to ensure that angina patients are effectively managed. These Read codes are embedded into the QOF templates of computer systems currently in use in practice. The relevance of the major part of the SIGN guideline to the QOF process has made its implementation much more successful than that of some other guidelines that do not have an incentivised process to follow in primary care.

Table 2: QOF indicators relevant to angina3*

CHD 1 All patients with angina should be included in the CHD register once CHD is confirmed
CHD 2 This indicator relates to the percentage of patients with newly diagnosed angina (diagnosed after 1 April 2003), who are referred for exercise testing and/or specialist assessment
CHD 5, CHD 6, CHD 7, CHD 8, CHD 9, CHD 10, CHD 12 All these indicators relate to and include angina patients if their angina symptoms are confirmed to be the result of underlying atherosclerotic CHD
CHD 11 This applies if the patient has angina and has had a previous MI treated with ACEi or angiotensin II receptor blocker

*text has been adapted to relate to angina rather than CHD
CHD=coronary heart disease; MI=myocardial infarction; ACEi=angiotensin-converting enzyme inhibitor

Table 3: Main recommendations relating to relief of symptoms

 
B Following initial assessment in primary care, patients with suspected angina should, wherever possible, have the diagnosis confirmed and the severity of the underlying coronary heart disease assessed in the chest pain evaluation service that offers the earliest appointment, regardless of model
A Beta blockers should be used as first-line therapy for the relief of symptoms of stable angina
A Sublingual glyceryl trinitrate tablets or spray should be used for the immediate relief of angina and before performing activities that are known to bring on angina
A Patients who are intolerant of beta blockers should be treated with either rate-limiting calcium channel blockers, long-acting nitrates, or nicorandil
A When adequate control of anginal symptoms is not achieved with beta-blockade, a calcium channel blocker should be added
A All patients with stable angina due to atherosclerotic disease should receive long-term standard aspirin and statin therapy
A All patients with stable angina should be considered for treatment with angiotensin-converting enzyme inhibitors
B Patients with stable angina whose symptoms remain uncontrolled or who are experiencing reduced physical functioning despite optimal medical therapy should be considered for the Angina Plan
A Patients presenting with angina and with a diagnosis of coronary heart disease should receive long-term structured follow up in primary care
This material was reproduced with kind permission of the Scottish Intercollegiate Guidelines Network

Rapid access chest pain clinics

A variety of models of care have been proposed as the optimum approach to the investigation and management of patients presenting with angina symptoms. The National Service Framework for CHD identified RACPCs as an immediate priority for the NHS in England.4 This service has grown rapidly and there are now 160 RACPCs across England with the capacity to see 96% of patients within 2 weeks of referral. From 2002 to 2006, the number of patients being referred to these clinics doubled to 212,000 per annum. Of the patients referred, just over 50% were characterised as having chest pain of cardiac origin that required further investigation.5 Evidence published in 2007 indicates that some of the lower risk patients, who were initially found at the RACPC not to have cardiac disease, comprised one-third of the group of patients who went on to have acute events.6 This would suggest that more work is required to determine whether RACPCs are possibly also not identifying patient’s with milder coronary disease.

The SIGN guideline development group did not recommend the RACPC model as the ideal approach for the investigation of angina patients. They emphasised instead that a local chest pain evaluation service offering a comprehensive and prompt examination was the priority, but that it needed to take into account local circumstances and existing facilities (this is in line with indicator CHD 2,3 see Table 2).

Optimal medical therapy

For patients diagnosed with stable CHD, the initial management strategy of pharmacological therapy and reference to lifestyle changes outlined in the guideline has been reinforced by publication of the COURAGE trial.7 This trial included 2287 patients with objective evidence of myocardial ischaemia due to underlying CHD, who were assigned to undergo percutaneous coronary intervention (PCI) with optimal medical therapy or to continue only on optimal medical therapy. Follow up was for a period of 2.5–7.0 years and, as an initial therapy, PCI in addition to optimal medical therapy was not found to reduce the risk of death, myocardial infarction, or other major cardiovascular cause of death. However, in certain patients there is still a place for revascularisation in line with the recommendations illustrated in Figure 2.

Figure 2: Consideration for revascularisation

Consider for revascularisation

CABG=coronary artery bypass graft; PCI=percutaneous coronary intervention

Medical management

Relief of symptoms

The main recommendations from the SIGN guideline relating to relief of symptoms are listed in Table 3. Patients with symptoms of angina should be given sublingual glyceryl trinitrate tablets or spray for immediate relief or to use before performing activities that are known to bring on angina (Grade A). However, beta blockers remain the first-line therapy for relief of symptoms of stable angina (Grade A, and CHD 103). They act by reducing heart rate and blood pressure, which improves the balance between oxygen supply and demand. They also decrease the end systolic stress and contractility with an increase in diastolic perfusion time leading to increased coronary blood flow.

There is no evidence that one beta blocker is better than another in respect of their use in stable angina. When adequate control of angina symptoms is not achieved with a beta blocker, a calcium channel blocker should be added (Grade A). In practice, the calcium channel blocker of choice is likely to be a dihydropyridine derivative; this is because rate-limiting calcium channel blockers such as diltiazem should be used with caution when combined with beta blockers because of the risk of severe bradycardia and heart block, and verapamil should not be used in combination because of possible heart failure.

Intolerance and contraindications to beta blockers

Beta blockers are contraindicated in patients with severe bradycardia and atrioventricular block, sick sinus syndrome, decompensated heart failure, and asthma. They are also not tolerated in a large proportion of patients because of a variety of symptoms, including fatigue, cold periphery, and erectile dysfunction.8 In case of intolerance, alternatives include a rate-limiting calcium channel blocker, a long-acting nitrate, or nicorandil (Grade A). A newer drug, ivabradine, has been shown to be as effective as the beta blocker atenolol in relieving symptoms,9 and, although it has not been compared with a rate-limiting calcium channel blocker, it compared well with amlodipine in terms of relief of symptoms.10 One small study has shown that ivabradine does not have an appreciable effect on the respiratory function or symptoms of patients with asthma.11

Use of three drugs for controlling symptoms

Although the evidence for combining three drugs is limited, this is likely to be tried in practice if symptoms are not controlled, and is often attempted before considering revascularisation. However, if symptoms remain uncontrolled, further cardiological review should be considered. Addition of a long-acting nitrate has been the traditional approach, although nicorandil has been shown to be comparable to both the dihydropyridine derivative amlodipine and the rate-limiting calcium channel blocker diltiazem in reducing angina.

On the basis of the IONA trial, which included 5126 patients, nicorandil was shown significantly to reduce the combined end point of CHD death, non-fatal myocardial infarction, or unplanned hospitalisation for cardiac chest pain.12 It has also been shown that the addition of nicorandil to therapy is cost effective in reducing hospitalisation costs.13 On the basis of this evidence the drug is now licensed for reduction in risk of coronary events in patients with chronic stable angina, with its benefit extending into the next category of prevention of future vascular events.

Drugs to reduce future vascular events

Patients with angina as a result of CHD should receive long-term statin and aspirin therapy. (Grade A, CHD 7, 8 and 9). Although no patients with angina without a prior myocardial infarction were recruited to the CAPRIE trial,14 clopidogrel would seem to be a reasonable alternative for patients unable to tolerate or who are sensitive to aspirin.15 Patients with stable angina, based on an analysis of all the evidence, should also be considered for treatment with an angiotensin-converting enzyme inhibitor (Grade A, CHD 11 if previous myocardial infarction) even if left ventricular systolic dysfunction is not present.

Improving quality of life

One aspect of the guideline that is much more difficult to implement by changing clinical practice is addressing quality of life and psychological issues. A straightforward approach would be for all primary care organisations to consider introducing the Angina Plan (www.anginaplan.org.uk) for all patients being commenced on treatment for angina. This plan comprises a patient-held workbook and relaxation programme delivered by a trained health professional in primary care, which can lead to a reduction of angina and physical limitation, and also to a reduction in anxiety and depression.16

Updating the guideline

The publication of new evidence on a regular basis challenges guideline developers to ensure that any guideline is continually updated to reflect any change in the evidence underpinning their recommendations. Clinical guidance on stable angina is scheduled for publication by NICE in December 2010, and the SIGN guideline on the Management of stable angina is also expected to be considered for review early that year. In the meantime, the guideline from SIGN remains the only current national guideline for the management of stable angina and should be used as the basis for the development of local protocols and practice guidance across the UK.

Click here for CPD questions on this article and the SIGN guideline on the management of stable angina

  • Approximately 30% of people who go on to have vascular events are not identified at an RACPC
  • A local chest pain evaluation service can offer a comprehensive examination and take account of local circumstances and existing facilities
  • PCI in addition to optimal medical therapy does not reduce mortality
  • Nicorandil is cost effective (£8.18–£15.54 per month 10 mg/20 mg doses) and decreases mortality in patients when prescribed alongside beta blockers and calcium channel blockers
  • Tariff prices:a cardiology outpatient £194 (new), £96 (follow up)
  1. Scottish Intercollegiate Guidelines Network. Management of stable angina. A national clinical guideline (SIGN 96). Edinburgh: SIGN, 2007.
  2. Connolly S, Collier T, Khugputh R et al. Brain natriuretic peptide testing for angina in a rapid-access chest pain clinic. QJM 2007; 100 (12): 779–783.
  3. British Medical Association. www.bma.org.uk/ap.nsf/Content/focusQOF0308
  4. Department of Health. Coronary heart disease: national service framework for coronary heart disease—modern standards and service models. London: DH, 2000.
  5. Boyle R. Value of rapid-access chest pain clinics. Heart 2007; 93 (4): 415–416.
  6. Sekhri N, Feder G, Junghans C et al. How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients. Heart 2007; 93 (4): 458–463.
  7. Boden W, O’Rourke R, Teo K et al; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; 356 (15): 1503–1156.
  8. British National Formulary 55 March 2008. London: BMJ Publishing Group Ltd, Royal Pharmaceutical Society, 2008.
  9. Tardif J, Ford I, Tendera M et al; and the INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005; 26 (23): 2529–2536.
  10. Ruzyllo W, Tendera M, Ford I, Fox K. Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial. Drugs 2007; 67 (3): 393–405.
  11. Babu K, Gadzik F, Holgate S. Absence of respiratory effects with ivabradine in patients with asthma. Br J Clin Pharmacol 2008 Mar 13 epub
  12. IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002; 359 (9314): 1269–1275.
  13. Walker A, McMurray J, Stewart S et al. Economic evaluation of the impact of nicorandil in angina (IONA) trial. Heart 2006; 92 (5): 619–624.
  14. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 (9038): 1329–1339.
  15. National Institute for Health and Care Excellence. Clopidogrel and modified-release dipyridamole in the prevention of occlusive vascular events. Technology Appraisal 90. London: NICE, 2005.
  16. Lewin R, Furze G, Robinson J et al. A randomised controlled trial of a self-management plan for patients with newly diagnosed angina. Br J Gen Pract 2002; 52 (476): 194–196, 199–201.G

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