Alternative Nitrate Options for HFpEF Patient with Skin Reaction to Nitroglycerin Patch
For a patient with HFpEF, DM, and HTN experiencing a local skin reaction to nitroglycerin 0.2 mg/hr patch, oral isosorbide dinitrate is the most appropriate alternative therapy.
Rationale for Switching to Oral Nitrates
Nitrates remain an important therapeutic option in HFpEF patients, particularly those with comorbid hypertension. The local skin reaction to the nitroglycerin patch is likely an irritant contact dermatitis, which occurs in approximately 5.3% of patients using transdermal nitroglycerin systems 1.
Equivalent Dosing Options
Isosorbide dinitrate (oral):
- First-line alternative: 20-30 mg orally three times daily
- Administer with a nitrate-free interval of 10-14 hours (typically overnight) to prevent tolerance
- Bioavailability is approximately 25% with extensive first-pass metabolism 2
Isosorbide mononitrate (extended-release):
- 30-60 mg once daily in the morning
- Provides consistent 24-hour coverage with fewer headaches 3
- Better compliance profile than multiple daily dosing regimens
Important Considerations
Preventing Nitrate Tolerance
- A daily nitrate-free interval of 10-14 hours is essential to maintain efficacy 3, 2
- For oral isosorbide dinitrate, this can be achieved by administering doses during waking hours only
- Continuous nitrate exposure beyond 24 hours leads to complete loss of efficacy 3
Monitoring for Side Effects
- Common side effects include headache and hypotension
- Monitor blood pressure closely after initiating therapy
- Start with lower doses and titrate as needed based on symptom control
Contraindications
- Avoid nitrates if:
- Systolic blood pressure <90 mmHg
- Concurrent use of phosphodiesterase-5 inhibitors (within 24-48 hours)
- Right ventricular infarction
- Severe aortic stenosis 3
Evidence for Nitrate Use in HFpEF
Recent research has questioned whether reducing pulmonary capillary wedge pressure (PCWP) with nitrates improves exercise capacity in HFpEF patients. A 2023 study found that while sublingual nitroglycerin lowered PCWP during exercise, it did not improve peak oxygen uptake 4. However, nitrates remain valuable for symptom management and blood pressure control in these patients.
Alternative Approaches if Nitrates Not Tolerated
If the patient cannot tolerate any form of nitrate therapy, consider:
Optimizing other HFpEF therapies:
- ACE inhibitors or ARBs for blood pressure control
- Beta-blockers (if tolerated)
- Diuretics for volume management 5
For patients with persistent angina symptoms:
- Calcium channel blockers (with caution in HF patients)
- Ranolazine (though limited evidence in HFpEF)
Application Site Management
If continuing with transdermal nitrates is necessary:
- Rotate application sites
- Consider using a different transdermal system, as changing to a different system has been shown to reduce the incidence of local reactions 1
- Apply hydrocortisone cream to affected areas after patch removal
Remember to maintain the nitrate-free interval regardless of the formulation chosen to preserve therapeutic efficacy and prevent tolerance development.