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Nitroglycerin Use in the Initial Management of Ischemic Pain from Acute Myocardial Infarction (NSTEMI, STEMI)

Summary:

Most clinicians will administer nitroglycerin in the management of acute coronary syndrome (ACS) by using sublingual dissolving tablets (SL), SL spray or topical (though the 2014 NSTEMI guidelines specify SL administration). Recommended dosing is 0.3 to 0.4 mg every 5 minutes up to 3 doses and then switching to IV nitroglycerin if the chest persists and there are no contraindications.  However it is worth noting that:

  • There have been no clinical trials (in the pre-hospital or in the acute care/in-hospital setting) that have evaluated this commonly used, recommended regimen, or dosage form of nitrate  In addition, the references cited by most current guidelines are not only limited, but also do not reflect studies using the recommended regimen.  This regimen is likely used out of convenience, ease of administration, and extrapolation of data based on the amount of nitroglycerin per minute that patients receive from SL dosage forms. 
  • Most clinical trials were done between 1979 and 1995, and started off with IV nitroglycerin infusions with the goal of lowering the systolic blood pressure (SBP) by 20% or titrated to improvement in angina, while keeping the SBP above 90 mm Hg.
  • While some trials described a small difference in mortality, a mortality benefit with the use of nitrates in acute myocardial infarction (AMI) was not really found until the publication of the Cochrane Review in 2009.  They reported that the mortality benefit (4 to 8 deaths prevented per 1,000) was restricted to the first 48 hours of treatment of AMI.  The Cochrane review finding of a reduction in mortality was consistent with an earlier systematic review published in Lancet 1988. 
  • Most studies (which used IV nitroglycerin infusions) reported benefits in not only reducing chest pain and blood pressure, but reductions in the size and/or expansion of the MI as measured by CK levels. 
  • Of note, there are some data in patients getting thrombolytic therapy that suggest nitroglycerin may negatively impact the efficacy of the thrombolytics. This needs to be studied in a well-designed, randomized, controlled trial.


Contraindications & Clinical Considerations
:

Contraindications to the use of any form of nitroglycerin include:

  • Hypotension (usually reported to be SBP < 90 mm Hg) or a > 30 mm Hg drop from the patient's baseline
  • Bradycardia (< 50 beats per min)
  • Tachycardia
  • Patients experiencing a right ventricular infarction
  • Use of avanafil, sildenafil or vardenafil within 24 hrs, or tadalafil within 48 hrs, due to the risk of significant hypotension and/or cardiogenic shock 
  • Note:
    • Morphine can also dilate the venous system and result in a reduction in preload, which can worsen tachycardia and cause hypotension in patients with right sided MIs, since they are preload dependent.


Author: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Editor: Dylan Kellogg, MD
Last Reviewed: August 2015

Supporting Guidelines

  • 2014 AHA/ACC NSTEMI Guidelines: 
    "Patients with NSTE-ACS with continuing ischemic pain should receive sublingual nitroglycerin (0.3 mg to 0.4 mg) every 5 minutes for up to 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin if not contraindicated. (Class I, Level of Evidence: C)"

    • Reference: Amsterdam EA et al.  2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.  Circulation 2014:[Epub ahead of print]. PubMed

    2013 AHA/ACC STEMI Guidelines: 
    "Intravenous nitroglycerin may be useful to treat patients with STEMI and hypertension or HF. Nitrates should not be given to patients with hypotension, marked bradycardia or tachycardia, RV infarction, or 5'phosphodiesterase inhibitor use within the previous 24 to 48 hours. There is no role for the routine use of oral nitrates in the convalescent phase of STEMI."

    • Reference: O'Gara PT et al.  2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.  Circulation 2013;127(4):e362-425. PubMed

    2010 AHA ACLS Guidelines: 
    "Although it is reasonable to consider the early administration of nitroglycerin in selected patients without contraindications, insufficient evidence exists to support or refute the routine administration of nitroglycerin in the ED or prehospital setting in patients with a suspected ACS. There may be some benefit if nitroglycerin administration results in pain relief." 

    • O'Connor RE et al. Part 9. Acute Coronary Syndromes: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation 2010;122:S422-S465. PubMed

Landmark or Original Studies

  • Goldstein RE et al. Clinical and circulatory effects of isosorbide dinitrate. Comparison with nitroglycerin. Circulation 1971;43(5):629-40. PubMed
  • Chiche P et al. A randomized trial of prolonged nitroglycerin infusion in acute myocardial infarction. Circulation (Suppl II) 1979;165:59-60.
  • Bussman WD et al. Reduction of CK and CK-MB indexes of infarct size by intravenous nitroglycerin. Circulation 1981;63(3):615-22. PubMed
  • Flaherty JT et al. A randomized prospective trial of intravenous nitroglycerin in patients with acute myocardial infarction. Circulation 1983;68(3):576-588. PubMed
  • Jaffe AS et al. Reduction of infarct size in patients with inferior infarction with intravenous glyceryl trinitrate. A randomized study. Br Heart J 1983;49(5):452-60. PubMed
  • Lis Y et al. A preliminary double-blind study of intravenous nitroglycerin in acute myocardial infarction. Intensive Care Med 1984;10(4):179-84. PubMed
  • Fitzgerald LJ et al. The effects of oral isosorbide 5-mononitrate on morality following acute myocardial infarction: a multicenter study. Eur Heart J 1990;11:120-126. PubMed
  • Jugdutt BI et al. Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location. Circulation 1988;78)4):906-19. PubMed
  • Anonymous. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet 1994;343(8906):1115-22. PubMed
  • Anonymous. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected myocardial infarction. Lancet 1995;345(8951):669-685. PubMed
  • Nicolini FA et al. Concurrent nitroglycerin therapy impairs tissue-type plasminogen activator-induced thrombolysis in patients with acute myocardial infarction. Am J Cardiol 1994;74(7):662-6. PubMed
  • Charvat J et al. Beneficial effect of intravenous nitroglycerin in patients with non-Q myocardial infarction. Cardiologia 1990;35(1):49-54. PubMed
  • Gobel EJ et al. Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris. Lancet 1995;346(899-18992):1653-7. PubMed

Supporting Studies

  • Perez MI, et al. Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event. Cochrane Database Syst Rev 2009;Oct 7;(4):CD006743. PubMed
  • Yusuf S et al. Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomized trials. Lancet 1988;1(8594):1088-92. PubMed

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MESH Terms or Keywords

  • Nitroglycerin NTG Chest Pain, Nitroglycerin Angina, Nitroglycerin Use in ACS, Nitroglycerin Use in NSTEMI, Nitroglycerin Use in Acute MI AMI