Is there a mortality benefit to nitroglycerin or morphine in acute coronary syndrome (ACS)?

From the Guidelines

There is no clear mortality benefit to nitroglycerin or morphine in acute coronary syndrome (ACS), and their use should be guided by symptom severity rather than an expectation of mortality benefit. While nitroglycerin effectively relieves chest pain by dilating coronary arteries and reducing cardiac preload and afterload, studies have not demonstrated that it improves survival outcomes, as noted in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. Similarly, morphine, while effective for pain relief at doses of 2-4 mg IV with additional 2-8 mg as needed, has not been shown to reduce mortality in ACS. In fact, some observational data, such as the study by Meine et al in 2017, suggest morphine might be associated with worse outcomes in certain ACS patients, with increased rates of adverse clinical outcomes, including myocardial infarction and death 1.

Key points to consider when using these medications in ACS include:

• Nitroglycerin is beneficial in patients with heart failure, hypertension, or symptoms that are not relieved with sublingual nitroglycerin and administration of a beta blocker, as stated in the 2014 AHA/ACC guideline 1.
• Morphine may be administered during intravenous nitroglycerin therapy with blood pressure monitoring, but its use should not preclude the use of other anti-ischemic therapies with proven benefits, as noted in the same guideline 1.
• Blood pressure should be monitored closely with both medications, as hypotension is a potential side effect that could worsen cardiac perfusion.
• The decision to administer nitrates should not preclude therapy with other proven mortality-reducing interventions, such as beta blockers, as emphasized in the 2014 AHA/ACC guideline 1.

Overall, while nitroglycerin and morphine are important for symptom management and comfort care in ACS, their use should be tailored to the individual patient's needs and guided by symptom severity, rather than an expectation of mortality benefit.

From the FDA Drug Label

The benefits of sublingual nitroglycerin in patients with acute myocardial infarction or congestive heart failure have not been established. There is no direct evidence of a mortality benefit to nitroglycerin in acute coronary syndrome, as the benefits have not been established 2.

• No information is provided about morphine. The FDA drug label does not answer the question about morphine.

From the Research

Mortality Benefit of Nitroglycerin and Morphine in Acute Coronary Syndrome

• The use of nitroglycerin and morphine in acute coronary syndrome (ACS) is a common practice to relieve chest pain, but the mortality benefit of these medications is not well established 3.
• A systematic review found that prehospital administration of nitroglycerin was associated with significantly lower 30-day and 1-year mortality compared with no prehospital administration, with odds ratios (OR) of 0.34 (95% confidence interval [CI] 0.24-0.50) and 0.38 (95% CI 0.29-0.50), respectively 4.
• However, the certainty of evidence for the mortality benefit of nitroglycerin and morphine in ACS is very low, and further investigation is needed to determine the benefit of these agents 4.
• The management of ACS typically involves a combination of medications, including antiplatelet therapy, anticoagulation, and vasodilators like nitroglycerin, as well as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in selected patients 5, 3.
• Morphine is often used to relieve chest pain in ACS, but its effect on mortality is not well established, and its use should be individualized based on patient-specific factors 3.

Key Components of ACS Management

• Early risk stratification and individualized treatment approach are essential in managing patients with ACS 5.
• Key components of ACS management include coronary revascularization, dual antiplatelet therapy, anticoagulation, and consideration of adjuvant agents like β blockers, inhibitors of the renin-angiotensin system, and HMG-coenzyme A reductase inhibitors 5, 3.
• The use of nitroglycerin and morphine should be considered as part of a comprehensive treatment plan for ACS, but their mortality benefit is not well established and requires further investigation 4.