Actions for Practice Teams

Medical management of stable angina

due to coronary artery disease

June 2012

www.pctsla.org @MedManKeele
 2
Actions for Practice Teams Why are we looking at this?
• 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.
 3
Actions for Practice Teams What are we covering?
The following slides provide information on:

• 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
 4
Actions for Practice Teams Introduction
• 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

• 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)
 5
Actions for Practice Teams Features of stable angina 6,7

• 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

• 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 Features of acute coronary 6

syndrome6
• 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

o pain in the chest or arms, back or jaw for longer than 15 minutes
o chest pain with nausea and vomiting, sweating, breathlessness
o chest pain associated with haemodynamic instability
o new onset chest pain, or abrupt deterioration in previously stable
angina, with recurrent chest pain occurring frequently and with
little or no exertion.
 7
Actions for Practice Teams NICE CG95: diagnosis of stable angina 6

• 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.

• NICE do not recommend use of exercise ECG to diagnose or exclude

stable angina in people without known CAD.
 8
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
typical or atypical symptoms,
assume estimate > 90%. For women Lo 3% 9% 23% 49%
> 70 years assume estimate of 61- Men

Non-anginal chest
90% EXCEPT women at high risk Hi 35% 47% 59% 69%
with typical symptoms (estimate
risk > 90%) Lo 1% 2% 4% 9%

pain
• Values are % of people at each mid-
decade age with significant CAD.
• Hi = High risk = Diabetes, smoking Women
and hyperlipidaemia (total Hi 19% 22% 25% 29%
cholesterol > 6.47 mmol/litre)
• Lo = Low risk = None of these three
• The shaded area represents people Lo 8% 21% 45% 71%
with symptoms of non-angina chest Men
Atypical
pain, who would not be investigated angina
Hi 59% 70% 79% 86%
for stable angina routinely.
NOTE: These results are likely to Lo 2% 5% 10% 20%
overestimate CAD in primary care Women
populations. If there are resting ECG Hi 39% 43% 47% 51%
ST-T changes or Q waves, the
likelihood of CAD is higher in each cell Lo 30% 51% 80% 93%
of the table. Men
Typical
angina

Hi 88% 92% 95% 97%

Lo 10% 20% 38% 56%
Women
 9
Actions for Practice Teams Education and lifestyle advice
• 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.
 Secondary prevention of CV disease in patients with 10
Actions for Practice Teams stable angina8

For most patients, treatment

Offer a statin to all patients in line with NICE guideline should be initiated with
on lipid modification (CG67) simvastatin 40 mg.

Consider aspirin 75 mg daily Consider risk of bleeding and co-

morbidities.

NICE recommend ACEi for some

Consider angiotensin-converting enzyme inhibitors
(ACEi) if the patient has diabetes. ACEi should be
continued if already taken for other comorbidities.
patients with hypertension
(CG127), heart failure (CG108),
diabetes (CG87, CG15), chronic
kidney disease (CG73) or post-MI
(CG48)

Initiate antihypertensive therapy, if appropriate.

Manage other co-morbidities including diabetes and
renal disease.
Review existing medication for exacerbating drugs
(e.g. NSAIDs).
Actions for Practice Teams NICE CG126: 11

Anti-anginal drug therapy8

Offer a short acting nitrate (for immediate short term relief) 1 and
either a beta blocker or calcium channel blocker (CCB) as first-line treatment 2

If symptoms not controlled on either If both beta blocker or CCB not

beta-blocker or CCB, consider other If beta blocker or CCB not tolerated
consider switching to other option tolerated consider monotherapy
option or use both drugs together3 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
 12
Actions for Practice Teams Which beta-blocker?
• 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

 13
Actions for Practice Teams Which calcium channel blocker?
• 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 Other anti-anginal drugs: long-acting 14

nitrates
• 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.
 15
Actions for Practice Teams Other anti-anginal drugs: nicorandil
• Treatment option if first-line therapies inadequately control
symptoms or are contraindicated/not tolerated.8

• Potassium-channel activator with a nitrate component.

• Headache is a common side effect.9

• 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

• 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

 16
Actions for Practice Teams Other anti-anginal drugs: ivabradine
• 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

 17
Actions for Practice Teams Other anti-anginal drugs: ranolazine
• NICE guidance includes ranolazine as treatment option if first-
line 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

 18
Actions for Practice Teams Annual Cost of anti-anginal drugs
ivabradine (Procoralan®) £1,047
(5 mg bd - 7.5 mg bd) £524
ranolazine (Ranexa®) £596
(500 mg bd - 750 mg bd) £596
isosorbide mononitrate M/R (Monomax SR®) £231
(60 mg M/R bd)
isosorbide mononitrate
(20 mg tds) £23
nicorandil £155
(10 mg bd - 20 mg bd) £84
diltiazem (Angitil SR®) £135
(120 mg tds)
diltiazem
(60 mg tds) £67
felodipine £110
(5 mg - 10 mg) £55
metoprolol £68
(50 mg bd - 100 mg tds) £19
verapamil £65
(80 mg tds - 120 mg tds) £29
bisoprolol £30
(10 mg od -10 mg bd) £15
amlodipine £13
(5 mg - 10 mg) £12
atenolol £11
(100 mg)
£0 £200 £400 £600 £800 £1,000 £1,200

Prices: Drug Tariff May-12 and MIMS Jun-12 Maximum Minimum

 19
Actions for Practice Teams Investigation and revascularisation 8

• 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
 20
Actions for Practice Teams What are the key actions/issues?
• 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.

• 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
 21
Actions for Practice Teams Key actions/issues continued..
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)
 22
Actions for Practice Teams References
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/Integratedperfomancemeasuresmonitori
ng/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;27:1341-
81.
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-onset-cg95/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>