Chronic stable angina treatment potassium channel openers

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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.


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]


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]


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) "


  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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