Chronic stable angina treatment potassium channel openers: Difference between revisions

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__NOTOC__
{{Chronic stable angina}}
{{Chronic stable angina}}


'''Editors-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org] Phone:617-632-7753; '''Associate Editor-In-Chief:''' [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]]
'''Editors-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] Phone:617-632-7753; '''Associate Editor-In-Chief:''' [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]]


==Overview==
==Overview==
[[Nicorandil]] has both, '''anti-anginal effects''' due to [[Chronic stable angina treatment nitrates#Mechanisms of benefit|nitrate-like]] and ATP-sensitive potassium channel activating properties and provides '''cardio-protective effects''' as well. Therefore, nicorandil usage in addition to standard [[Chronic stable angina pharmacotherapy overview| anti-anginal therapy]] may be indicated in patients who are intolerant to [[Chronic stable angina treatment beta blockers|beta-blocker]] therapy or in whom [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy ([[Chronic stable angina treatment calcium channel blockers|CCB]] is unsuccessful.<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref><ref name="pmid14658416"> (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14658416 Nicorandil for angina--an update.] ''Drug Ther Bull'' 41 (11):86-8. PMID: [http://pubmed.gov/14658416 14658416]</ref><ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>
[[Nicorandil]] has both, anti-anginal effects due to [[Chronic stable angina treatment nitrates#Mechanisms of benefit|nitrate-like]] and ATP-sensitive potassium channel activating properties and provides cardio-protective effects as well. Therefore, nicorandil usage in addition to standard [[Chronic stable angina medical therapy| anti-anginal therapy]] may be indicated in patients who are intolerant to [[Chronic stable angina treatment beta blockers|beta-blocker]] therapy or in whom [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy [[Chronic stable angina treatment calcium channel blockers|CCB]] is unsuccessful.<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref><ref name="pmid14658416"> (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14658416 Nicorandil for angina--an update.] ''Drug Ther Bull'' 41 (11):86-8. PMID: [http://pubmed.gov/14658416 14658416]</ref><ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>


==Mechanisms of benefit==
==Potassium Channel Openers==
*Nicorandil has both, [[Chronic stable angina treatment nitrates#Mechanisms of benefit|nitrate-like]] and ATP-sensitive potassium channel activating properties and therefore, maintains a '''balanced coronary and peripheral [[vasodilation]]''' with subsequent reduction in both [[preload]] and [[afterload]].<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref>
===Mechanisms of Benefit===
*Nicorandil has both, [[Chronic stable angina treatment nitrates#Mechanisms of benefit|nitrate-like]] and ATP-sensitive potassium channel activating properties and therefore, maintains a balanced coronary and peripheral [[vasodilation]] with subsequent reduction in both [[preload]] and [[afterload]].<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref>


*Nicorandil, due to its ATP-sensitive potassium channel activating property, simulates a process of '''ischemic pre-conditioning''' which involves multiple episodes of sub-lethal [[myocardial ischemia]] consequent to severe [[ischemic]] insult followed by periods of [[reperfusion]]<ref name="pmid3769170">Murry CE, Jennings RB, Reimer KA (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3769170 Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.] ''Circulation'' 74 (5):1124-36. PMID: [http://pubmed.gov/3769170 3769170]</ref> and hence prevents subsequent ischemic-reperfusion injury.<ref name="pmid8660253">Gross GJ, Mei DA, Schultz JJ, Mizumura T (1996) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8660253 Criteria for a mediator or effector of myocardial preconditioning: do KATP channels meet the requirements?] ''Basic Res Cardiol'' 91 (1):31-4. PMID: [http://pubmed.gov/8660253 8660253]</ref>
*Nicorandil, due to its ATP-sensitive potassium channel activating property, simulates a process of ischemic pre-conditioning which involves multiple episodes of sub-lethal [[myocardial ischemia]] consequent to severe [[ischemic]] insult followed by periods of [[reperfusion]]<ref name="pmid3769170">Murry CE, Jennings RB, Reimer KA (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3769170 Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.] ''Circulation'' 74 (5):1124-36. PMID: [http://pubmed.gov/3769170 3769170]</ref> and hence prevents subsequent ischemic-reperfusion injury.<ref name="pmid8660253">Gross GJ, Mei DA, Schultz JJ, Mizumura T (1996) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8660253 Criteria for a mediator or effector of myocardial preconditioning: do KATP channels meet the requirements?] ''Basic Res Cardiol'' 91 (1):31-4. PMID: [http://pubmed.gov/8660253 8660253]</ref>


*In patients with stable angina, studies have shown nicorandil to reduce the frequency of coronary events and hence, provide '''cardio-protective effects'''.<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref><ref name="pmid14658416"> (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14658416 Nicorandil for angina--an update.] ''Drug Ther Bull'' 41 (11):86-8. PMID: [http://pubmed.gov/14658416 14658416]</ref>
*In patients with stable angina, studies have shown nicorandil to reduce the frequency of coronary events and hence, provide cardio-protective effects.<ref name="pmid11085202">Markham A, Plosker GL, Goa KL (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11085202 Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.] ''Drugs'' 60 (4):955-74. PMID: [http://pubmed.gov/11085202 11085202]</ref><ref name="pmid14658416"> (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14658416 Nicorandil for angina--an update.] ''Drug Ther Bull'' 41 (11):86-8. PMID: [http://pubmed.gov/14658416 14658416]</ref>


==Indications==
===Indications===
In cases where [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy ([[Chronic stable angina treatment calcium channel blockers|CCB]] with [[Chronic stable angina treatment beta blockers|beta-blocker]]) is unsuccessful or in patients with [[Chronic stable angina treatment beta blockers|beta-blocker]] intolerance, [[nicorandil]] may be used as a supplement in addition to standard [[Chronic stable angina pharmacotherapy overview| anti-anginal therapy]].<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>
In cases where [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy ([[Chronic stable angina treatment calcium channel blockers|CCB]] with [[Chronic stable angina treatment beta blockers|beta-blocker]]) is unsuccessful or in patients with [[Chronic stable angina treatment beta blockers|beta-blocker]] intolerance, [[nicorandil]] may be used as a supplement in addition to standard [[Chronic stable angina medical therapy| anti-anginal therapy]].<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>


==Dosage==
===Dosage===
A dose of 20 mg twice daily has shown to be effective for the [[Chronic stable angina secondary prevention|prevention of angina]].<ref name="pmid10190531">Rajaratnam R, Brieger DB, Hawkins R, Freedman SB (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10190531 Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris.] ''Am J Cardiol'' 83 (7):1120-4, A9. PMID: [http://pubmed.gov/10190531 10190531]</ref>
A dose of 20 mg twice daily has shown to be effective for the [[Chronic stable angina secondary prevention|prevention of angina]].<ref name="pmid10190531">Rajaratnam R, Brieger DB, Hawkins R, Freedman SB (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10190531 Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris.] ''Am J Cardiol'' 83 (7):1120-4, A9. PMID: [http://pubmed.gov/10190531 10190531]</ref>


==Adverse effects==
===Adverse Effects===
*[[Flushing]]
*[[Flushing]]
*[[Palpitations]]
*[[Palpitations]]
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*Peri-anal, ileal and peri-stromal [[ulceration]] are recently reported side effects.
*Peri-anal, ileal and peri-stromal [[ulceration]] are recently reported side effects.


==Supportive trial data==
===Supportive Trial Data===
In the '''IONA trial''', 5126 patients in addition to standard [[Chronic stable angina pharmacotherapy overview| anti-anginal therapy]] were randomized to receive either 20 mg [[nicorandil]] twice daily or placebo to assess the effect of nicorandil in the reduction of frequency of coronary events in men and women with [[Chronic stable angina definition|stable angina]]. The primary end-point of all cause of mortality, non-fatal [[MI]] or unplanned hospital admission for [[Chest pain|cardiac chest pain]] during a mean follow-up of 1.6 years revealed a significant difference between the two groups: 13.1% in the nicorandil group and 15.5% in the placebo group ''(p=0.014)''. Thus, the study concluded that in patients with stable angina, [[Chronic stable angina pharmacotherapy overview|anti-anginal therapy]] with [[nicorandil]] reduced the frequency of major coronary events and significantly improved clinical outcomes.<ref name="pmid11965271">IONA Study Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11965271 Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial.] ''Lancet'' 359 (9314):1269-75. [http://dx.doi.org/10.1016/S0140-6736(02)08265-X DOI:10.1016/S0140-6736(02)08265-X] PMID: [http://pubmed.gov/11965271 11965271]</ref>
* In the ''IONA'' trial, 5126 patients were randomized to receive either 20 mg [[nicorandil]] twice daily or placebo in addition to standard [[Chronic stable angina medical therapy| anti-anginal therapy]]. The goal of the study was to assess the effect of nicorandil in the reduction of frequency of coronary events in men and women with [[Chronic stable angina definition|stable angina]]. The primary end-point of all cause of mortality, non-fatal [[MI]] or unplanned hospital admission for [[Chest pain|cardiac chest pain]] during a mean follow-up of 1.6 years revealed a significant difference between the two groups: 13.1% in the nicorandil group and 15.5% in the placebo group (p=0.014). Thus, the study concluded that in patients with stable angina, [[Chronic stable angina medical therapy|anti-anginal therapy]] with [[nicorandil]] reduced the frequency of major coronary events and significantly improved clinical outcomes.<ref name="pmid11965271">IONA Study Group (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11965271 Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial.] ''Lancet'' 359 (9314):1269-75. [http://dx.doi.org/10.1016/S0140-6736(02)08265-X DOI:10.1016/S0140-6736(02)08265-X] PMID: [http://pubmed.gov/11965271 11965271]</ref>


==ESC Guidelines- Pharmacotherapy to Improve Symptoms and/or Reduce Ischaemia in patients with stable angina (DO NOT EDIT) <ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>==
==ESC Guidelines- Pharmacotherapy to Improve Symptoms and/or Reduce Ischaemia in Patients with Stable Angina (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>==
{{cquote|
===[[European society of cardiology#Classes of Recommendations|Class I]]===
'''1.''' In case of [[Chronic stable angina treatment beta blockers|beta-blocker]] intolerance or poor efficacy attempt monotherapy with a [[Chronic stable angina treatment calcium channel blockers|CCB]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'', [[Chronic stable angina treatment nitrates|long-acting nitrate]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'', or [[nicorandil]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''


===[[European society of cardiology#Classes of Recommendations|Class IIa]]===
===Nicorandil (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367}}</ref>===
'''1.''' If [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy ([[Chronic stable angina treatment calcium channel blockers|CCB]] with [[Chronic stable angina treatment beta blockers|beta-blocker]]) is unsuccessful, substitute the [[Chronic stable angina treatment calcium channel blockers|CCB]] with a [[Chronic stable angina treatment nitrates|long-acting nitrate]] or [[nicorandil]]. Be careful to avoid [[Chronic stable angina treatment nitrates|nitrate tolerance]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])''}}


==Vote on and Suggest Revisions to the Current Guidelines==
{| class="wikitable"
*[[The Living Guidelines: Chronic Stable Angina Pectoris | The Chronic Stable Angina Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines]]
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In case of [[Chronic stable angina treatment beta blockers|beta-blocker]] intolerance or poor efficacy attempt monotherapy with a [[Chronic stable angina treatment calcium channel blockers|CCB]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'', [[Chronic stable angina treatment nitrates|long-acting nitrate]] ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'', or [[nicorandil]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|}


==Sources==
{| class="wikitable"
*Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology <ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=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. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= |url=url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf]}} </ref>
|-
 
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]]
*The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina <ref name="pmid10351980">Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10351980 ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina).] ''Circulation'' 99 (21):2829-48. [http://circ.ahajournals.org/content/99/21/2829.full.pdf] PMID: [http://pubmed.gov/10351980 10351980]</ref>
|-
 
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' If [[Chronic stable angina treatment calcium channel blockers|CCB]] monotherapy or combination therapy ([[Chronic stable angina treatment calcium channel blockers|CCB]] with [[Chronic stable angina treatment beta blockers|beta-blocker]]) is unsuccessful, substitute the [[Chronic stable angina treatment calcium channel blockers|CCB]] with a [[Chronic stable angina treatment nitrates|long-acting nitrate]] or [[nicorandil]]. Be careful to avoid [[Chronic stable angina treatment nitrates|nitrate tolerance]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
*TheACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina <ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref>
|}
 
*The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina <ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>


==References==
==References==
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{{WikiDoc Sources}}
{{WikiDoc Sources}}


[[Category:Disease]]
[[Category:Ischemic heart diseases]]
[[Category:Ischemic heart diseases]]
[[Category:Disease state]]
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[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]
[[Category:Up-To-Date]]
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Latest revision as of 21:39, 5 February 2013

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Editors-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Associate Editor-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S.

Overview

Nicorandil has both, anti-anginal effects due to nitrate-like and ATP-sensitive potassium channel activating properties and provides cardio-protective effects as well. Therefore, nicorandil usage in addition to standard anti-anginal therapy may be indicated in patients who are intolerant to beta-blocker therapy or in whom CCB monotherapy or combination therapy CCB is unsuccessful.[1][2][3]

Potassium Channel Openers

Mechanisms of Benefit

  • Nicorandil has both, nitrate-like and ATP-sensitive potassium channel activating properties and therefore, maintains a balanced coronary and peripheral vasodilation with subsequent reduction in both preload and afterload.[1]
  • Nicorandil, due to its ATP-sensitive potassium channel activating property, simulates a process of ischemic pre-conditioning which involves multiple episodes of sub-lethal myocardial ischemia consequent to severe ischemic insult followed by periods of reperfusion[4] and hence prevents subsequent ischemic-reperfusion injury.[5]
  • In patients with stable angina, studies have shown nicorandil to reduce the frequency of coronary events and hence, provide cardio-protective effects.[1][2]

Indications

In cases where CCB monotherapy or combination therapy (CCB with beta-blocker) is unsuccessful or in patients with beta-blocker intolerance, nicorandil may be used as a supplement in addition to standard anti-anginal therapy.[3]

Dosage

A dose of 20 mg twice daily has shown to be effective for the prevention of angina.[6]

Adverse Effects

Supportive Trial Data

  • In the IONA trial, 5126 patients were randomized to receive either 20 mg nicorandil twice daily or placebo in addition to standard anti-anginal therapy. The goal of the study was to assess the effect of nicorandil in the reduction of frequency of coronary events in men and women with stable angina. The primary end-point of all cause of mortality, non-fatal MI or unplanned hospital admission for cardiac chest pain during a mean follow-up of 1.6 years revealed a significant difference between the two groups: 13.1% in the nicorandil group and 15.5% in the placebo group (p=0.014). Thus, the study concluded that in patients with stable angina, anti-anginal therapy with nicorandil reduced the frequency of major coronary events and significantly improved clinical outcomes.[7]

ESC Guidelines- Pharmacotherapy to Improve Symptoms and/or Reduce Ischaemia in Patients with Stable Angina (DO NOT EDIT)[3]

Nicorandil (DO NOT EDIT)[3]

Class I
"1. In case of beta-blocker intolerance or poor efficacy attempt monotherapy with a CCB (Level of Evidence: A), long-acting nitrate (Level of Evidence: C), or nicorandil. (Level of Evidence: C) "
Class IIa
"1. If CCB monotherapy or combination therapy (CCB with beta-blocker) is unsuccessful, substitute the CCB with a long-acting nitrate or nicorandil. Be careful to avoid nitrate tolerance. (Level of Evidence: C) "

References

  1. ↑ 1.0 1.1 1.2 Markham A, Plosker GL, Goa KL (2000) Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects. Drugs 60 (4):955-74. PMID: 11085202
  2. ↑ 2.0 2.1 (2003) Nicorandil for angina--an update. Drug Ther Bull 41 (11):86-8. PMID: 14658416
  3. ↑ 3.0 3.1 3.2 3.3 Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). "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. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367.
  4. ↑ Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74 (5):1124-36. PMID: 3769170
  5. ↑ Gross GJ, Mei DA, Schultz JJ, Mizumura T (1996) Criteria for a mediator or effector of myocardial preconditioning: do KATP channels meet the requirements? Basic Res Cardiol 91 (1):31-4. PMID: 8660253
  6. ↑ Rajaratnam R, Brieger DB, Hawkins R, Freedman SB (1999) Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris. Am J Cardiol 83 (7):1120-4, A9. PMID: 10190531
  7. ↑ IONA Study Group (2002) Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 359 (9314):1269-75. DOI:10.1016/S0140-6736(02)08265-X PMID: 11965271

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