Actions for Practice Teams
Medical management of stable angina
due to coronary artery disease
June 2012
www.pctsla.org
Actions for Practice Teams
Why are we looking at this?
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Approximately 140,000 men and 116,000 women in the West
Midlands have angina.1
Approximately 1% of visits to a GP are because of chest pain.2
Between April 2010 to March 2011, approximately 11,000
patients were referred to rapid access chest pain clinics in the
West Midlands3
Between April 2010 and March 2011, approximately 10,000
emergency hospital admissions in the West Midlands were
because of angina pectoris.4
Optimal management of angina could reduce complications of
the disease, improve patient quality of life, decrease GP and
hospital attendance and costs to the NHS.
Actions for Practice Teams
What are we covering?
The following slides provide information on:
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Features and diagnosis of stable angina
Education and lifestyle advice
Secondary prevention of cardiovascular disease in patients
with stable angina
Anti-anginal drug therapy
o Short-acting nitrates
o Beta-blockers
o Calcium channel blockers
o Long-acting nitrates
o Nicorandil
o Ivabradine
o Ranolazine
3
Actions for Practice Teams
Introduction
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Angina is caused by restriction of blood flow and oxygen to the
heart, usually due to obstructive coronary artery disease
(CAD)5-7
Angina adversely affects quality of life and increases the risk of
myocardial infarction and mortality. In clinical trials of stable
angina:
o annual mortality is approximately 0.9 to 1.4%.5
o annual incidence of non-fatal myocardial infarction (MI) is
between 0.5% and 2.6%. 5
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Risk factors for angina are5,6:
o Older age
o Male sex
o Cardiovascular risk factors (e.g. history of smoking, diabetes,
hypertension, dyslipidaemia, family history of premature CAD)
o History of documented CAD (e.g. MI, coronary revascularisation)
Actions for Practice Teams
Features of stable
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angina6,7
5
Symptoms of typical stable angina are:
o central or left-sided chest pain or discomfort (may radiate to neck,
jaw, shoulders and arms)
o precipitated by physical exertion
o relieved by rest or GTN within about 5 minutes
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People with:
o Non-angina chest pain have one or none of these features
o Atypical angina: two features
o Typical angina: all three features
Actions for Practice Teams
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Features of acute coronary
syndrome6
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Stable angina should be clearly distinguished from acute
coronary syndrome (MI/unstable angina) as these patients
require urgent hospital admission.
Patients with acute coronary syndrome (ACS) may present with
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pain in the chest or arms, back or jaw for longer than 15 minutes
chest pain with nausea and vomiting, sweating, breathlessness
chest pain associated with haemodynamic instability
new onset chest pain, or abrupt deterioration in previously stable
angina, with recurrent chest pain occurring frequently and with
little or no exertion.
Actions for Practice Teams
NICE CG95: diagnosis of stable
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angina6
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Stable angina should be diagnosed according to NICE guidance. Local
guidance should also be consulted.
In people presenting with intermittent stable chest pain, NICE
recommend that stable angina diagnosis should be based on: clinical
assessment alone or clinical assessment + diagnostic tests
If a person presenting with stable chest pain has features of typical
angina (based on clinical assessment) + estimated likelihood of CAD
is greater than 90%, further diagnostic testing is not necessary.
Manage as angina.
In people without confirmed CAD, in whom diagnosis of stable angina
is uncertain (people with estimated likelihood of CAD 10 to 90%),
clinical assessment + further diagnostic tests are required.
o Treat as stable angina while waiting for the results.
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NICE do not recommend use of exercise ECG to diagnose or exclude
stable angina in people without known CAD.
Non-anginal
chest pain
Atypical
angina
typical or atypical symptoms,
assume estimate > 90%. For women
> 70 years assume estimate of 6190% EXCEPT women at high risk
with typical symptoms (estimate
risk > 90%)
• Values are % of people at each middecade age with significant CAD.
• Hi = High risk = Diabetes, smoking
and hyperlipidaemia (total
cholesterol > 6.47 mmol/litre)
• Lo = Low risk = None of these three
• The shaded area represents people
with symptoms of non-angina chest
pain, who would not be
investigated for stable angina
routinely.
NOTE: These results are likely to
overestimate CAD in primary care
populations. If there are resting ECG
ST-T changes or Q waves, the
likelihood of CAD is higher in each cell
of the table.
Typical
angina
Actions for Practice Teams
NICE (CG95): Percentage of people estimated to have
CAD according to typicality of symptoms, age, sex and
risk factors6
• For men aged > 70 years with
Age (years)
35
45
55
65
Men
Women
Men
Women
Men
Women
8
Lo
3%
9%
23%
49%
Hi
35%
47%
59%
69%
Lo
1%
2%
4%
9%
Hi
19%
22%
25%
29%
Lo
8%
21%
45%
71%
Hi
59%
70%
79%
86%
Lo
2%
5%
10%
20%
Hi
39%
43%
47%
51%
Lo
30%
51%
80%
93%
Hi
88%
92%
95%
97%
Lo
10%
20%
38%
56%
Hi
78%
79%
82%
84%
Actions for Practice Teams
Education and lifestyle advice
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9
Offer advice including information on long-term course, risks
and benefits of treatment. Address concerns (e.g. impact of
stress, anxiety or depression, physical exertion including
sexual activity). Dispel myths.
Advise on self-management skills such as pacing activities and
goal setting.
Advise on lifestyle changes including smoking cessation,
healthy diet with adequate intake of fish, fruit and vegetables,
weight loss and control of lipid levels, alcohol within safe limits
LGV and PSV licence holders should inform the DVLA
Advise patients to seek professional help urgently if their
angina suddenly worsens.
Actions for Practice Teams
Secondary prevention of CV disease in patients with
stable angina8
Offer a statin to all patients in line with NICE
guideline on lipid modification (CG67)
Consider aspirin 75 mg daily
Consider angiotensin-converting enzyme
inhibitors (ACEi) if the patient has diabetes.
ACEi should be continued if already taken for
other comorbidities.
Initiate antihypertensive therapy, if appropriate.
Manage other co-morbidities including diabetes
and renal disease.
Review existing medication for exacerbating
drugs (e.g. NSAIDs).
For most patients, treatment
should be initiated with
simvastatin 40 mg.
Consider risk of bleeding and comorbidities.
NICE recommend ACEi for some
patients with hypertension
(CG127), heart failure (CG108),
diabetes (CG87, CG15), chronic
kidney disease (CG73) or post-MI
(CG48)
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Actions for Practice Teams
NICE CG126:
Anti-anginal drug therapy8
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Offer a short acting nitrate (for immediate short term relief)1 and
either a beta blocker or calcium channel blocker (CCB) as first-line treatment2
If symptoms not controlled on
either beta-blocker or CCB,
consider other option or use both
drugs together3
If beta blocker or CCB not
tolerated consider switching to
other option
If both beta blocker or CCB not
tolerated consider monotherapy
with a long-acting nitrate or
ivabradine or nicorandil or
ranolazine
If symptoms not fully controlled,
consider adding a long-acting
nitrate or ivabradine4 or
nicorandil5 or ranolazine
If symptoms not satisfactorily controlled with two anti-anginal drugs and the person is waiting for
revascularisation (or revascularisation not appropriate), consider adding third anti-anginal drug.
Do not offer a third anti-anginal drug if stable angina is controlled with two drugs
1) Advise on how and when to use and explain side effects. Dose should be repeated if pain has not gone 5
mins after first dose. Call ambulance if pain not gone 5 mins after second dose.
2) Review response to all drug treatment 2 to 4 weeks after starting or changing treatment. Titrate dose
(according to symptom control) up to maximum tolerated dose
3) When combining a calcium channel blocker with a beta-blocker, use a dihydropyridine CCB (e.g.
amlodipine or felodipine)
4) When combining ivabradine with a CCB, use a dihydropyridine CCB
5) Nicorandil is not currently licensed for use as add-on therapy
Actions for Practice Teams
Which beta-blocker?
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No good evidence that one beta-blocker is more effective in
than another in managing stable angina.9
Select according to contraindications, co-morbidities, patient
preference and cost.8
Avoid beta-blockers if history of asthma or bronchospasm.
Contraindicated in decompensated heart failure or critical
peripheral vascular disease.9
Do not combine a beta blocker with verapamil and use caution
with diltiazem.9
Sudden withdrawal may cause exacerbation of angina9
Actions for Practice Teams
Which calcium channel blocker?
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CCBs include dihydropyridines (e.g. amlodipine, felodipine),
benzothiapines (diltiazem), and phenylalkylamines (verapamil).9
Important differences between CCB classes but evidence does not
support a recommendation to use a specific CCB. Choose according
to contraindications, co-morbidities, patient preference and cost.8
Dihydropyridines may cause reflex tachycardia, flushing, headache,
and ankle swelling. Short acting formulations of nifedipine are not
recommended.8,9
Diltiazem and verapamil may cause bradycardia
o Avoid in heart failure9
o Do not combine a beta blocker with verapamil, caution with
diltiazem9
o Constipation common with verapamil9
Prescribe SR nifedipine and diltiazem (other than 60 mg) by brand
Actions for Practice Teams
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Other anti-anginal drugs: long-acting
nitrates
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Treatment option if first-line therapies inadequately control symptoms
or are contraindicated/not tolerated.8
Long acting nitrates are less expensive than ivabradine and
ranolazine.
Isosorbide mononitrate is generally preferred to isosorbide dinitrate.
Continuous use of long-acting nitrates induces tolerance, with
reduced therapeutic effect
o Standard release isosorbide mononitrate should be used in an
asymmetric dosing interval to minimize development of tolerance9
o Modified release isosorbide mononitrate should be used once
daily to maintain a nitrate-low period9
MR isosorbide mononitrate more expensive than standard-release. If
an MR preparation is appropriate, brand name prescribing of the
lowest cost MR preparation is recommended.
Actions for Practice Teams
Other anti-anginal drugs: nicorandil
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Treatment option if first-line therapies inadequately control
symptoms or are contraindicated/not tolerated.8
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Potassium-channel activator with a nitrate component.
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Headache is a common side effect.9
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MHRA safety advice (2008)10:
o Consider nicorandil treatment as a possible cause in people who
present with symptoms of gastrointestinal ulceration.
o Ulcers are refractory to treatment; withdraw nicorandil.
o Withdraw only under the supervision of cardiologist
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Advise patients to not drive or operate machinery until it is
established that nicorandil does not impair their performance9
Not currently licensed for use as add-on therapy.9
Actions for Practice Teams
Other anti-anginal drugs: ivabradine
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Treatment option for patients in sinus rhythm if first-line
therapies inadequately control symptoms or are
contraindicated/not tolerated.8
Lowers heart rate at rest and during exercise. (Note: ventricular
rate at rest should not be allowed to fall below 50 beats per
minute).11
If combined with a calcium channel blocker, use a
dihydropyridine calcium channel blocker (e.g. MR nifedipine,
amlodopine or felodipine).8
Visual disturbances (phosphenes) are a common adverse
effect.11
Data on long term efficacy and safety are limited.8
Actions for Practice Teams
Other anti-anginal drugs: ranolazine
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NICE guidance includes ranolazine as treatment option if firstline therapies inadequately control symptoms or are
contraindicated/not tolerated.8
Ranolazine increases exercise time and reduces frequency of
angina attacks but effects are modest and clinical significance
is uncertain.8,13 Data on long-term efficacy and safety are
limited.
Safety concerns: associated with QT interval prolongation and
syncope, contraindications include some other cardiac
agents.9
MTRAC do not recommend ranolazine for prescribing.12 SMC
does not recommend use of ranolazine in NHS Scotland.13
Patients taking ranolazine should carry a “patient alert card.”14
Actions for Practice Teams
Annual Cost of anti-anginal drugs
ivabradine (Procoralan®)
(5 mg bd - 7.5 mg bd)
ranolazine (Ranexa®)
(500 mg bd - 750 mg bd)
isosorbide mononitrate M/R (Monomax SR®)
(60 mg M/R bd)
isosorbide mononitrate
(20 mg tds)
nicorandil
(10 mg bd - 20 mg bd)
diltiazem (Angitil SR®)
(120 mg tds)
diltiazem
(60 mg tds)
felodipine
(5 mg - 10 mg)
metoprolol
(50 mg bd - 100 mg tds)
verapamil
(80 mg tds - 120 mg tds)
bisoprolol
(10 mg od -10 mg bd)
amlodipine
(5 mg - 10 mg)
atenolol
(100 mg)
£1,047
£524
£596
£596
£231
£23
£155
£84
£135
£67
£110
£55
£68
£19
£65
£29
£30
£15
£13
£12
£11
£0
£200
Maximum
Prices: Drug Tariff May-12 and MIMS Jun-12
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£400
Minimum
£600
£800
£1,000
£1,200
Actions for Practice Teams
Investigation and
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revascularisation8
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If symptoms are not adequately controlled with optimal medical
treatment (two anti-anginal drugs + secondary prevention
drugs), consider revascularisation (CABG or PCI)
CABG also option to improve prognosis in a specific subgroup
of patients with left main stem or proximal three-vessel disease
Actions for Practice Teams
What are the key actions/issues?
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Do you know how many emergency hospital admissions from
your practice are due to angina pectoris?
Are you aware of the local care pathways for people with stable
angina?
o Care pathways for chronic stable angina currently may vary from
area to area according to local commissioners and the local
services available.
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Review current prescribing for patients with stable angina to
ensure that it is in-line with NICE and MHRA guidance. For
example:
o Short-acting nitrates (e.g. glyceryl trinitrate) should be prescribed
for all patients with stable angina
o For first-line treatment , use either a beta-blocker or a CCB
o Anti-anginal drugs other than beta-blockers or CCBs should not
be used as first-line treatments for stable angina
Actions for Practice Teams
Key actions/issues continued..
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o Check patients prescribed a beta-blocker do not have underlying
asthma or bronchospasm
o Check for patients prescribed a beta-blocker with verapamil
(could lead to extreme bradycardia)
o Check for patients with heart failure prescribed
diltiazem/verapamil (may cause deterioration)
o Check for patients prescribed ivabradine with verapamil/diltiazem
(not recommended)
o Review use of potentially exacerbating drugs (e.g. NSAIDs)
Actions for Practice Teams
References
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1. Coronary Heart Disease Statistics 2010 edition. British Heart Foundation Statistics website.
http://www.bhf.org.uk/research/statistics.aspx
2. Stewart S, Murphy NF, Walker A et al. The current cost of angina pectoris to the National Health Service in the UK. Heart
2003;89:848-53.
3. Rapid Access Chest Pain Clinic. Department of Health. May 2011.
http://www.dh.gov.uk/en/Publicationsandstatistics/Statistics/Performancedataandstatistics/Integratedperfomancemeasuresm
onitoring/DH_112551
4. Hospital Episode Statistics. April 2009 to March 2011.
5. Fox K, Garcia MA, Ardissino D et al. Guidelines on the management of stable angina pectoris: executive summary: The
Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006;27:134181.
6. Chest pain of recent onset: Assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin.
CG95. National Institute of Health and Clinical Excellence. 2010. http://publications.nice.org.uk/chest-pain-of-recent-onsetcg95/introduction <accessed 5/2012>
7. Jokhu P, Curzen N. Ischaemic heart disease: stable angina. Medicine 2010; 38: 414-420.
8. The management of stable angina (CG126). National Institute of Health and Clinical Excellence. 2011.
http://www.nice.org.uk/Search.do?searchText=angina&newsearch=true&x=0&y=0#/search/?reload
9. BNF 63 (2012) British National Formulary. 63rd edn. London: British Medical Association and Royal Pharmaceutical Society
of Great Britain.
10. Nicorandil: gastrointestinal ulceration. Drug Safety Update. 2008. Medicines and Healthcare products Regulatory Agency
http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085019 <accessed 5/2012>
11. Procoralan. Electronic medicines compendium. 2012.
http://www.medicines.org.uk/EMC/medicine/17188/SPC/Procoralan/#INDICATIONS <accessed 5/2012>12)
12. Ranolazine (Ranexa). Midlands Therapeutics Review and Advisory Committee. 2009.
http://www.keele.ac.uk/pharmacy/mtrac/mtracverdictsheetsescas/ <accessed 5/2012>
13. Ranolazine, 375mg, 500mg and 750mg prolonged-release tablets (Ranexa®). Scottish Medicines Consortium. 2012.
http://www.scottishmedicines.org.uk/files/advice/ranolazine_Ranexa_2nd_Resubmission_FINAL_Dec_2011_for_website.pdf
<accessed 5/2012>
14. A.Menarini Pharma U.K.S.R.L. Ranexa 375 mg prolonged-release tablets. Electronic medicines compendium. 2012.
http://www.medicines.org.uk/EMC/medicine/21402/SPC/Ranexa+prolonged-release+tablets/ <accessed 5/2012>