What are the considerations for using isosorbide mononitrate (isosorbide mononitrate) in a patient with end-stage renal disease (ESRD) undergoing dialysis and angina pectoris?

Isosorbide Mononitrate Use in Dialysis Patients with Angina

Isosorbide mononitrate can be used safely in dialysis patients with angina pectoris, but requires careful attention to volume status, hypotension risk, and dosing strategy to avoid tolerance while maintaining antianginal efficacy.

Key Safety Considerations in Dialysis Patients

Volume Status and Hypotension Risk

• Dialysis patients are at particularly high risk for severe hypotension with nitrates due to frequent volume depletion from ultrafiltration 1
• Isosorbide mononitrate should be used with extreme caution in patients who may be volume depleted or already hypotensive, as even small doses can cause severe hypotension, particularly with upright posture 1
• Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris 1
• The vasodilating effects are additive with other vasodilators, requiring dose adjustments when used with calcium channel blockers or other antihypertensive agents 1

Dialysis-Specific Limitations

• Dialysis is known to be ineffective in removing isosorbide mononitrate from the body in cases of overdose, meaning drug accumulation and prolonged effects are concerns 1
• In patients with renal disease, therapy resulting in central volume expansion (which may be needed to treat nitrate-induced hypotension) is not without hazard and may be subtle and difficult 1
• Treatment of isosorbide mononitrate overdose in dialysis patients may require invasive monitoring 1

Treatment Approach for Angina in Dialysis Patients

General Management Principles

• All dialysis patients presenting with acute coronary syndromes should be treated as in the non-dialysis population, with specific attention to drugs that have altered clearances in kidney failure 2
• Standard therapies including antiplatelet agents, beta-blockers, and lipid-lowering agents should be used despite the lack of dialysis-specific clinical trials 2
• For chronic coronary artery disease management, the same principles apply with careful monitoring 2

Dosing Strategy to Prevent Tolerance

• The most effective way to prescribe isosorbide mononitrate for angina appears to be conventional formulation at 20 mg two or three times daily, rather than higher doses or once-daily sustained-release formulations 3
• Tolerance to antianginal and anti-ischemic effects develops rapidly if used in higher doses of 50 mg three times daily 3
• Once-daily sustained-release formulations (50-100 mg) show tolerance development within 20 hours, with no improvement in exercise tolerance at 4,20, or 24 hours after one week of therapy 3, 4
• A daily low-nitrate interval is required to prevent tolerance development—intermittent therapy with once-daily dosing or asymmetric dosing schedules prevents tolerance better than continuous exposure 5

Evidence from Dialysis-Specific Studies

Efficacy in Maintenance Hemodialysis Patients

• In a randomized controlled trial of 144 maintenance hemodialysis patients with hypertension, sustained-release isosorbide mononitrate (30-120 mg daily) effectively controlled blood pressure and improved left ventricular hypertrophy over 24 weeks 6
• Blood pressure was significantly lower in the nitrate group compared to non-nitrate group at 4,8,12, and 24 weeks 6
• Left ventricular mass index decreased significantly more in the nitrate group (from 65.3 to 51.2 g/m²·⁷) compared to the non-nitrate group (from 63.7 to 56.1 g/m²·⁷) 6
• The incidence of acute left heart failure was significantly lower in the nitrate group (1.4%) compared to non-nitrate group (11.1%) 6
• The incidence of adverse events was only 1.4%, demonstrating good tolerability 6
• Blood pressure was maintained between 12-24 weeks despite decreasing the total daily category and quantity of other antihypertensive drugs 6

Practical Implementation

Pre-Treatment Assessment

• Assess volume status carefully before initiating therapy, particularly in relation to the patient's dry weight and recent ultrafiltration 2, 1
• Review all concurrent antihypertensive medications and consider dose reductions, especially for agents taken immediately before dialysis 7
• Evaluate for intradialytic hypotension history, as this predicts higher risk with nitrate therapy 7
• Obtain baseline blood pressure in both supine and standing positions to assess orthostatic tolerance 1

Monitoring During Therapy

• Monitor for orthostatic hypotension, especially just after rising from recumbent or seated position 1
• Warn patients that treatment may be associated with light-headedness on standing, particularly if alcohol is consumed 1
• Headaches are common and are a marker of drug activity—patients should not alter dosing schedules to avoid headaches, as this may result in loss of antianginal efficacy 1
• Aspirin or acetaminophen can successfully relieve nitrate-induced headaches without affecting antianginal efficacy 1

Timing Relative to Dialysis

• Avoid administering short-acting antihypertensive medications and peripheral vasodilators immediately before dialysis sessions to prevent intradialytic hypotension 2
• Consider timing of nitrate administration to avoid peak effects during ultrafiltration periods when hypotension risk is highest 7

Common Pitfalls to Avoid

• Do not use continuous high-dose regimens (≥50 mg three times daily) as tolerance develops rapidly 3, 8
• Do not assume once-daily sustained-release formulations provide 24-hour coverage—tolerance develops within 20 hours 4
• Do not combine with multiple other vasodilators without careful blood pressure monitoring and dose adjustments 1
• Do not use in patients on polyacrylonitrile dialysis membranes due to risk of anaphylactoid reactions (this applies to ACE inhibitors, but caution is warranted with all vasoactive drugs) 2
• Do not rely on dialysis to remove the drug in case of overdose or adverse effects 1