What is the efficacy of nitroglycerin (glyceryl trinitrate) spray in managing hypertensive crises?

From the Guidelines

Nitroglycerin spray is not recommended for uncontrolled hypertension management. While nitroglycerin is effective for treating angina and acute heart failure, it's not appropriate for sustained blood pressure control in hypertensive emergencies or for chronic hypertension management.

Key Points to Consider

• For hypertensive emergencies (blood pressure >180/120 mmHg with organ damage), intravenous medications like labetalol, nicardipine, or clevidipine administered in a monitored setting are preferred 1.
• For urgent but non-emergency hypertension, oral medications like amlodipine 5-10mg, labetalol 200-400mg, or captopril 25mg are more appropriate.
• Nitroglycerin's blood pressure-lowering effect is too short-acting (15-30 minutes) and unpredictable for hypertension control, as it works by releasing nitric oxide, causing vasodilation primarily in veins rather than arteries, which doesn't provide the sustained arterial pressure reduction needed for hypertension management 1.
• Additionally, patients can develop tolerance to nitroglycerin quickly, further limiting its usefulness for ongoing blood pressure control.

Clinical Guidelines

• The 2019 ESC Council on Hypertension position document on the management of hypertensive emergencies recommends labetalol, nitroprusside, or nicardipine as first-line treatments for hypertensive emergencies 1.
• The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults recommends esmolol, labetalol, or nicardipine for acute aortic dissection, and clevidipine, nitroglycerin, or nitroprusside for acute pulmonary edema 1.

Conclusion Not Applicable

Instead, the following is a continuation of the discussion: In clinical practice, the choice of antihypertensive medication should be individualized based on the patient's underlying medical conditions, potential side effects, and the presence of any comorbidities.

Important Considerations

• The potential for adverse effects, such as profound hypotension, should be carefully considered, particularly in patients who are elderly, volume-depleted, or have used sildenafil within 24 hours 1.
• The development of nitrate tolerance can limit the effectiveness of nitroglycerin for ongoing blood pressure control. In summary, while nitroglycerin spray may have a role in certain acute cardiovascular conditions, it is not recommended for uncontrolled hypertension management due to its short-acting and unpredictable nature, as well as the potential for tolerance development. Instead, other antihypertensive medications, such as labetalol, nicardipine, or clevidipine, are preferred for hypertensive emergencies, and oral medications like amlodipine, labetalol, or captopril are more suitable for urgent but non-emergency hypertension.

From the FDA Drug Label

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload) Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear. Therapeutic doses of nitroglycerin may reduce systolic, diastolic, and mean arterial blood pressure

The effectiveness of nitroglycerin spray for uncontrolled hypertension is not directly addressed in the provided drug label. However, based on the information provided, nitroglycerin can:

• Reduce systolic, diastolic, and mean arterial blood pressure
• Produce arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure It is essential to note that the primary use of nitroglycerin is for the relief of angina, and its effectiveness for uncontrolled hypertension is not explicitly stated in the label 2.

From the Research

Effectiveness of Nitroglycerin Spray for Uncontrolled Hypertension

• The effectiveness of nitroglycerin spray for uncontrolled hypertension is supported by a study published in 2018 3, which found that sublingual nitroglycerin spray allowed for rapid blood pressure control in hypertensive emergencies and was a useful bridge during the time to prepare intravenous infusion.
• The study found that mean reduction of mean arterial blood pressure by 12.3 and 16.3% was achieved at 5 and 10 minutes after sublingual nitroglycerin, respectively 3.
• However, other studies have noted that nitroglycerin is not considered a first-line therapy for hypertensive crises due to its potential adverse effects and toxicities 4, 5.
• An alternative agent, clevidipine, has been shown to be effective in reducing blood pressure in patients with acute severe hypertension and has a more favorable safety profile compared to nitroglycerin 6.
• Another study published in 2015 found that topical nitroglycerin ointment may be effective in treating acute hypertension in hospitalized inpatients, with 42% of applications resulting in a decrease of 20 mm Hg or more in systolic blood pressure 7.

Comparison with Other Agents

• Clevidipine has been shown to be more effective than sodium nitroprusside or nitroglycerin in controlling acutely elevated blood pressure in the perioperative setting 6.
• Nicardipine and fenoldopam are also considered effective alternatives to nitroglycerin for the treatment of hypertensive emergencies 4, 5.

Safety and Tolerability

• Nitroglycerin has been associated with significant toxicities and adverse effects, including headache, nausea, and vomiting 6, 7.
• Clevidipine has been shown to have a similar safety profile to nitroglycerin, but with a lower incidence of adverse effects 6.