• For symptom relief:
• Sublingual glyceryl trinitrate (GTN) should be used for the rapid relief of symptoms of angina and before performing activities known to cause symptoms of angina.
• A beta-blocker should be prescribed as first-line regular treatment to reduce the symptoms of stable angina.
• If a beta-blocker is contraindicated or not tolerated, prescribe a calcium-channel blocker (CCB), a nitrate (such as isosorbide mononitrate), or nicorandil.
• Ivabradine is an alternative to a CCB, a nitrate, or nicorandil if a beta-blocker is contraindicated or not tolerated. However, there is less experience with its use in primary care, and it is significantly more expensive than alternative anti-anginal drugs. Primary care prescribers may wish to consider seeking advice from a specialist before initiating ivabradine in primary care, particularly if they are not familiar with its use.
• Ranolazine is not recommended for initiation in primary care.
• To improve the person's prognosis:
• All people with stable angina should be taking low-dose aspirin and a statin unless these are contraindicated or not tolerated.
• For information on antiplatelet prophylaxis, including advice on what to do if the person is allergic to aspirin or is at risk of gastrointestinal adverse effects, see the CKS topic on Antiplatelet treatment.
• For further information on prescribing a statin for the prevention of cardiovascular events, see the CKS topic on Lipid modification - CVD prevention.
• All people with stable angina should be considered for treatment with an angiotensin-converting enzyme (ACE) inhibitor.
• For people with stable angina and coexisting hypertension, diabetes, heart failure, asymptomatic left ventricular dysfunction, or previous myocardial infarction, an ACE inhibitor should be prescribed unless this is contraindicated or not tolerated.
• For people with stable angina and no coexisting indications for treatment with an ACE inhibitor, any anticipated benefit of treatment should be considered, alongside the costs and potential risks, on an individual basis.
• For more information, see the CKS topics on Diabetes type 2, Heart failure - chronic, Hypertension - not diabetic, and MI - secondary prevention.

These recommendations are based on guidelines from the Scottish Intercollegiate Guidelines Network [SIGN, 2007] and the European Society of Cardiology [Fox et al, 2006a].

Drugs for symptom control

• Sublingual glyceryl trinitrate (GTN)
• Weak evidence from a small trial indicates that sublingual GTN is effective in relieving the symptoms of angina compared with placebo [Parker et al, 1983]. In practice, sublingual GTN seems to rapidly relieve angina symptoms in most people.
• Beta-blockers
• The evidence for the efficacy of beta-blockers in treating the symptoms of angina is generally poor; however, they are widely recommended first-line for the treatment of angina [Fox et al, 2006a; SIGN, 2007]. Beta-blockers appear to have similar efficacy to calcium-channel blockers (CCBs).
• Beta-blockers are recommended first-line because good evidence indicates that they reduce mortality after myocardial infarction (MI) and in people with heart failure. There is also weak evidence that they reduce all-cause mortality in people with stable angina (and no prior MI or heart failure).
• They may be better tolerated and have fewer adverse effects than calcium-channel blockers or nitrates [DH, 2000].
• Calcium-channel blockers (CCBs)
• Evidence from meta-analyses and subsequent randomized controlled trials (RCTs) suggests that CCBs have similar efficacy to beta-blockers at reducing the symptoms of angina. CCBs are widely recommended for the treatment of stable angina as an alternative first-line treatment in people who cannot take a beta-blocker [Fox et al, 2006a; SIGN, 2007].
• Nitrates
• There is limited evidence on the efficacy of nitrates in the treatment of angina compared with either placebo or a comparator drug. Available data suggests that nitrates have similar efficacy to CCBs and beta-blockers.
• Some evidence from one RCT suggests that amlodipine is more effective than a nitrate in controlling exercise-induced angina in elderly people with coronary heart disease.
• Nitrates are recommended as an alternative to CCBs in people who cannot take a beta-blocker, on the basis of expert consensus [Fox et al, 2006a; SIGN, 2007].
• Nicorandil
• There is consensus that nicorandil is an effective treatment for angina [Fox et al, 2006a; SIGN, 2007]. Although data evidence from one study suggest that nicorandil may have prognostic benefits, further trials are needed to confirm this.
• Ivabradine
• Some evidence from RCTs indicates that ivabradine monotherapy improves symptoms in people with angina. Available evidence indicates that it does not affect prognosis.
• Some CKS expert reviewers recommend that ivabradine is suitable for initiation in primary care. Other CKS reviewers recommend that primary health care professionals seek advice from a specialist before initiating ivabradine in primary care. CKS recommends that primary care prescribers may wish to consider seeking advice from a specialist before initiating ivabradine in primary care, particularly if they are not familiar with ivabradine.
• Ivabradine is a black triangle drug — data on its long-term safety are limited, and it is being monitored intensively by the Commission on Human Medicines and the Medicines and Healthcare products Regulatory Agency [ABPI Medicines Compendium, 2010].
• Visual disturbances were commonly reported in people taking ivabradine in clinical studies. These were generally reported to be mild-to-moderate and resolved either during, or after stopping, treatment.
• Cardiovascular adverse effects have been noted in people taking ivabradine in clinical studies. Bradycardia has been noted in 3.3% of people taking ivabradine, particularly within the first 2 to 3 months of treatment. Only 0.5% of people have been reported to experience a severe bradycardia below or equal to 40 beats per minute.
• Psychiatric adverse effects (including one suicide) were reported in people taking ivabradine in two clinical studies.

Drugs for prognostic benefit

• Aspirin
• Strong evidence indicates that antiplatelet treatment reduces serious vascular events, non-fatal myocardial infarction, non-fatal stroke, and vascular mortality in people with cardiovascular disease [SIGN, 2007]. For a discussion of the evidence on antiplatelet treatment in people with previous MI, see the CKS topic on MI - secondary prevention.
• There is also evidence from one randomized placebo-controlled trial that in people with angina who are also taking a beta-blocker, aspirin reduces MI and sudden death [Juul-Möller et al, 1992].
• Statins
• Guidelines from the National Institute for Health and Clinical Excellence on lipid modification for the secondary prevention of cardiovascular disease [NICE, 2008] recommend that for secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors.
• For a full discussion of the use of statins for the secondary prevention of cardiovascular disease, see the CKS topic on Lipid modification - CVD prevention.
• Angiotensin-converting enzyme (ACE) inhibitors
• The benefits of ACE inhibitors after MI or in people with heart failure are well established. For further details, see the CKS topics on MI - secondary prevention and Heart failure - chronic.
• It is uncertain whether people with angina, but no other cardiovascular risk factors (for example previous MI, hypertension), are likely to benefit from taking an ACE inhibitor because evidence from large trials is conflicting [Fox et al, 2006b; SIGN, 2007].
• The European Society of Cardiology recommends that, in people with angina without coexisting indications for an ACE inhibitor (for example hypertension, heart failure, diabetes, or history of MI), the possible absolute benefits of treatment (which are greater in high-risk people with angina) should be weighed against the costs and risks of adverse effects [Fox et al, 2006a]. However, the view from the Joint British Societies is that ACE inhibitors are unlikely to offer any special benefit beyond that which can be attributed to reduction of blood pressure [British Cardiac Society et al, 2005].

Drugs that are not recommended

• Ranolazine
• Until further evidence of benefit and safety is available, ranolazine should only be initiated by a cardiologist.
• Some evidence from RCTs indicates that ranolazine improves symptoms in people with angina. Available evidence indicates that it does not affect prognosis.
• Ranolazine is a black triangle drug — data on its long-term safety are limited, and it is being monitored intensively by the Commission on Human Medicines and the Medicines and Healthcare products Regulatory Agency [ABPI Medicines Compendium, 2010].
• In clinical trials, the most common adverse effects were dizziness, nausea, asthenia, and constipation.
• There are concerns regarding QT prolongation noted in people taking ranolazine, and the increased likelihood of drug interactions.