From the Guidelines
Oral nitrate therapy, such as isosorbide dinitrate or isosorbide mononitrate, can be used to reduce pulmonary congestion and improve exercise tolerance in patients with heart failure with reduced ejection fraction (HFrEF) 1.
Key Considerations
- The primary use of oral nitrates is to treat angina by dilating blood vessels, but they can also be beneficial in patients with HFrEF.
- Common side effects of oral nitrates include headache, dizziness, and hypotension.
- To prevent nitrate tolerance, a nitrate-free interval of 10-14 hours daily is recommended, typically overnight 1.
- Patients should be cautioned not to take phosphodiesterase inhibitors (like sildenafil) within 24-48 hours of nitrate use due to the risk of severe hypotension.
Dosage and Administration
- Isosorbide dinitrate can be administered orally at a dose of 5-40 mg, while isosorbide mononitrate can be administered orally at a dose of 30-120 mg.
- Long-acting formulations like isosorbide mononitrate (typically 30-60 mg once daily) are preferred for prevention.
Monitoring and Precautions
- Patients should be monitored for signs of hypotension, such as dizziness or lightheadedness.
- Nitrates should be stored in their original containers, protected from light, and replaced regularly as they can lose potency over time.
- The use of nitrates in patients with severe anaemia or increased intracranial pressure should be avoided 1.
From the Research
Oral Nitrate Disease
- Oral nitrates are highly effective in terminating acute attacks of angina pectoris and in the prophylaxis of symptomatic and asymptomatic myocardial ischemia 2.
- The prevailing mechanism of nitrates in patients with chronic stable angina is preload reduction by venodilatation, which distinguishes them from beta and calcium-channel blockers 2.
- Nitrates can cause tolerance, which can be prevented by a daily low-nitrate interval, typically 10-12 hours per day 2, 3.
- Intermittent therapy with once-daily ingestion of high-dose sustained-release isosorbide dinitrate or isosorbide-5-mononitrate can prevent the development of tolerance 2, 3.
- Oral nitrates can be administered in various forms, including sublingual, oral, intravenous, and transdermal routes, with different dosing regimens and formulations available 3, 4.
Treatment and Management
- The dosage of nitrates used for angina pectoris can vary widely among individuals, and therapeutic resistance and tolerance can occur 5.
- Higher than recommended dosages of sublingual isosorbide dinitrate may be effective in treating angina pectoris in some patients 5.
- Once-daily sustained-release formulations of isosorbide mononitrate can provide optimal nitrate therapy and prevent tolerance 4.
- Other anti-ischemic drugs, such as ranolazine and ivabradine, can be used in combination with nitrates or as alternative therapies for chronic stable angina 6.
Adverse Effects and Interactions
- Common adverse effects of nitrates include headache, postural hypotension, facial erythema, vertigo, palpitations, and nausea and vomiting 3.
- Nitrates can interact with other vasodilators and calcium channel blockers, and can potentiate their effects 3.
- Indomethacin can inhibit the vasodilator effect of nitrates, and intravenous nitroglycerin can reduce the anticoagulant effect of heparin 3.