Background: Nitrates can help improve symptoms and ischemia in the setting of acute myocardial infarction. Current teaching holds that nitrates should be avoided in patients with potential right ventricular myocardial infarction (RVMI), due to the risk of decreasing preload and precipitating hypotension. This belief is based on a single 1989 study of 40 patients with RVMI and endorsed by both the AHA and ESC guidelines [2].

In that 1989 study, of the 40 patients with RV infarction 20 had a decrease in blood pressure of ≥30mmHg and associated symptoms after the administration of nitrates (SL, Oral, Transdermal, or IV) and 20 did not. The conclusion of this paper was that inferior AMI with RV involvement has a strong association with hypotensive response to nitrates. The major issue is the study is limited by the fact that we are given no information on dosage and multiple routes of administration making clinical application difficult. Better data is needed to guide management.

REBEL Cast 124: Nitrates in Right Sided MIs?

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Paper: Wilkinson-Stokes M et al. Adverse Events From Nitrate Administration During Right Ventricular Myocardial Infarction: A Systematic Review and Meta-Analysis. Emerg Med J 2023. PMID: 36180168

Clinical Question: Is giving nitrates to patients with right ventricular myocardial infarction (RVMI) associated with increased adverse events compared with nitrate administration to patients with myocardial infarctions in other regions of the heart?

What They Did:

A systematic review and meta-analysis
Exposure of interest: administration of nitrates, via any route and dose

Outcomes:

Primary: All forms of adverse events reported in the included studies (Hypotension, Bradycardia, AMS, Syncope, Cardiac Arrest)

Inclusion:

Patients diagnosed with AMI with a subset of the sample with RV myocardial infarction
Experimental and analytical observational study designs
Studies only published in English

Exclusion:

Patients with coronary vasospasm

Results:

5 studies included in the analysis
Only 2 observational studies using SL NTG 400mcg were used for the meta-analysis
- Adverse Events (Hypotension, Bradycardia, AMS, Syncope, Cardiac Arrest)
  - RVMI: 18/105 (17.1%)
  - Other MIs: 83/945 (8.8%)
  - RR 1.31 (95% CI 0.81 to 2.12)
  - No patients had cardiac arrest or death

Strengths:

Asks a clinically important question
Searched 6 different databases for relevant papers
All included studies underwent quality assessment using standard appraisal tools
If data was missing corresponding authors were contacted for the missing information

Limitations:

None of the included studies were RCTs
All studies samples were of combined inferior and RVMI making it difficult to determine the safety of nitrates during isolated RVMI
One of the included studies was only an abstract
Studies defined hypotension in different ways which could alter frequency of adverse events

Discussion:

Overall this review provides low certainty evidence that there is no statistically significant difference in the rate of adverse events when nitrates are administered to RVMI compared with other cardiac region MIs.
Hypotension is the primary adverse event reported. Nitrates have a serum half-life of 1 to 4 minutes and therefore hypotension is likely to be transient in nature
Transient hypotension is not really clinically meaningful, especially since it can be treated with cessation of nitrates and fluid challenges

Author Conclusion: “This review suggests that the AHA and ESC contraindications are not supported by evidence. Key limitations include all studies having concomitant inferior and RVMI, not evaluating beneficial effects and very low certainty of evidence. As adverse events are transient and easily managed, nitrates are a reasonable treatment modality to consider during RVMI on current evidence.”

Clinical Take Home Point: From a clinical perspective, the potential benefit of analgesia and reduced sympathetic stimulation in the setting of RVMI seems to outweigh the potential of transient hypotension with the use of nitrates. Although better studies are needed, this systematic review and meta-analysis argues against a contraindication against nitrates in the setting of RVMI and maybe one of precaution.

References:

Wilkinson-Stokes M et al. Adverse Events From Nitrate Administration During Right Ventricular Myocardial Infarction: A Systematic Review and Meta-Analysis. Emerg Med J 2023. PMID: 36180168
Ferguson JJ et al. Significance of Nitroglycerin-Induced Hypotension with Inferior Wall Acute Myocardial Infarction. Am J Cardiol 1989. PMID: 2502902
Neumar RW et al. Part 1. Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015. PMID: 26472989
Ibanez B et al. 2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-Segment Elevation. Eur Heart J 2018. PMID: 28886621

For More Thoughts on This Topic Checkout:

REBEL EM: The Death of MONA in ACS – Part III – Nitroglycerin

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami)

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