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Background Information on Nicorandil
Nicorandil is an anti-anginal therapy used in the management of angina – a
common and disabling heart disorder1.
It is estimated that 3-5% of the
population suffer from angina2,3.
What is Angina?
Angina is a sensation of pain or discomfort in the chest, usually associated
with coronary heart disease. It arises mainly when fatty deposits build up to
form ‘plaques’ on the insides of the arteries causing them to become
narrowed. This makes it difficult for the blood to get to the heart, leaving it
short of oxygen, and resulting in the pain of angina.
Angina is regarded as stable if it has been occurring over several weeks
without major deterioration and occurs in a predictable pattern. Angina in
such patients occurs when the heart needs more blood, for example, with a
particular level of physical activity or when the patient becomes emotionally
stressed.
Nicorandil and the Management of Angina
Treatment options for angina include beta-blockers, calcium antagonists,
nitrates and potassium channel activators. Nicorandil is a potassium channel
activator. It has a mechanism of action that involves dilating both the arteries
and veins allowing blood to flow more easily, thus allowing the heart to do less
work while allowing more oxygen to reach the heart muscle.
Nicorandil’s twice-daily dosage ensures 24-hour control4, to provide an
effective and tolerable therapy for many patients with angina.
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Nicorandil provides a promising treatment option for people who are faced
with angina. It is effective as monotherapy in up to 80% of patients 5 and can
be used in combination with other anti-anginal therapies without interactions
or an increase in adverse events6.
Nicorandil has become a widely used anti-anginal therapy since its launch in
Japan in 1984 and in Europe in 1994. The recently published PrescriptionEvent Monitoring Study of 13,260 people in the UK with angina (involving
86,760 patient months of treatment)7 has affirmed its good safety profile and
general tolerability.
Nicorandil & Protecting the Heart
Nicorandil is known to be an effective and well-tolerated anti-anginal therapy,
however, experts believe it may also help to protect the heart by mimicking a
natural process known as 'ischaemic preconditioning'. This is thought to help
the heart by limiting damage to the cardiac muscle during a heart attack. The
IONA# (Impact of Nicorandil in Angina) study was carried out to investigate
whether
nicorandil’s
apparent
cardioprotective
action
translates
into
measurable clinical benefit in patients with stable angina of effort.
What is Ischaemic Preconditioning?
If the heart muscle becomes starved of oxygen for a long period of time, part
of the heart tissue will become permanently damaged and die. However, on
the occasions when patients experience the pain of angina, the heart muscle
is starved of oxygen for only short periods of time, after which blood flows
back into the heart muscle. Instead of these short ischaemic episodes making
the heart weaker however, the heart has an in-built mechanism which uses
these episodes to help it protect itself; it becomes more resistant to lasting
tissue damage in subsequent severe angina episodes or heart attacks. This
phenomenon is known as ischaemic preconditioning.
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Nicorandil and Ischaemic Preconditioning
Experts think that this natural protective mechanism occurs as a result of the
opening of certain chemical channels in the heart tissue, which allow
potassium to flow across the membranes of the cells. In particular, a type
known as the ATP-sensitive potassium channel is thought to be involved.
Since nicorandil is an ATP-sensitive potassium channel opener, it is thought
that it may be able to mimic this natural phenomenon, and work to
precondition the heart tissue in a therapeutic way.
Animal studies carried out over the past few years have supported this
hypothesis – research has shown that treatment with nicorandil before
ischaemia occurs simulates this natural protective mechanism
8,9,10,11.
Recently, a study published in the European Heart Journal added further
clinical support for this idea – these results showed that nicorandil may offer
cardioprotective benefits in patients already receiving the maximum amount of
conventional anti-anginal therapy12. Researchers in this study saw a 90% and
70% reduction in the number of episodes of ventricular tachycardia and
supraventricular tachycardia respectively (when part of the heart beats with an
abnormally fast rhythm), and 50% fewer episodes of myocardial ischaemia
(oxygen shortage in the heart), compared to placebo. The authors concluded
that the beneficial effects of nicorandil evidenced in this study are most likely
due to ‘pharmacological preconditioning’.
References:
1. Eur Heart J (1997) 18: 394-413
2. Erens B and Primatesta P (1998) Health Survey for England Volume 1: Findings London,
The Stationery Office, pp14, 29, 37, 44
3. Marmot MG et al (1991) Lancet 337: 1387-1393
4. Wagner G. J Cardiovasc Pharmacol 1992; 20 (3) S86 – 92
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5. Krumenacker M, Roland E (1992) J Cardiovasc Pharmacol 20 (3): S93-102
6. Roland E (1993) Eur Heart J 14 (Suppl. B): 48-52
7. Dunn N, Freemantle S, Pearce G et al (1999) Pharmacoepidemiol and Drug Safety 8:
197-205
8. Yellon DM, Baxter GF, Marber MS (1996) Lancet 347: 1059-62
9. Parratt JR, Kane KA (1994) Cardiovasc Res 28: 783-87
10. Auchampach JA, Cavero I, Gross GJ (1992) J Cardiovasc Pharmacol 20(5): 765-71
11. Auchampach JA, Gross GJ (1993) Eur Heart J 14(Suppl B): 10-15
12. Patel DJ, Purcell HJ, Fox KM (1999) Eur Heart J 20: 51-7
#The
IONA study was a multi-centre, double blind controlled study with patients randomised to
receive placebo or nicorandil 10mg twice daily, increasing to 20mg twice daily after two
weeks. Treatment was given in addition to patients’ usual anti-anginal therapy for a duration
of between 12 and 36 months.
Nicorandil is marketed under the brand name Ikorel in UK, Ireland, Netherlands and
Australia; Ikorel and Adancor in France; Angicor in Denmark; Dancor in Switzerland and
Austria; Dancor and Nikoril in Portugal; Sigmart in Japan, Korea and Taiwan.
The trial received financial support from Aventis Pharma AG, Chugai Pharmaceutical Co., Ltd.
and Merck KGaA.
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