Should oral isosorbide dinitrate (Isoket) be discontinued when a patient develops a non‑ST‑segment elevation myocardial infarction (NSTEMI) during titration?

Should Oral Isosorbide Dinitrate Be Discontinued During NSTEMI?

No, you do not need to discontinue oral isosorbide dinitrate (Isoket) when a patient develops NSTEMI—in fact, nitrates are a Class I recommended therapy for ongoing ischemia in NSTEMI patients. 1

Guideline-Directed Nitrate Use in NSTEMI

Nitrates are explicitly recommended as first-line anti-ischemic therapy in NSTEMI, not contraindicated:

• Sublingual nitroglycerin (0.3–0.4 mg every 5 minutes for up to 3 doses) should be administered for ongoing ischemic chest pain 1
• Intravenous nitroglycerin is Class I indicated for the first 48 hours after NSTEMI presentation for treatment of persistent ischemia, heart failure, or hypertension 1
• Oral long-acting nitrates (including isosorbide dinitrate) are reasonable for recurrent ischemia after beta-blockers and initial nitrate therapy have been used 1

Critical Safety Considerations When Continuing Nitrates

Absolute contraindications that would require stopping nitrates:

• Systolic blood pressure <90 mmHg or >30 mmHg below baseline 1, 2
• Recent phosphodiesterase-5 inhibitor use (sildenafil within 24 hours, tadalafil within 48 hours, vardenafil timing uncertain) due to risk of profound hypotension, MI, and death 1, 3
• Right ventricular infarction where nitrates may critically reduce preload 4, 5
• Severe bradycardia (<50 bpm) or marked tachycardia (>100 bpm without heart failure) 4, 2

Practical Management Algorithm

If the patient is hemodynamically stable (SBP ≥100 mmHg, no contraindications):

1. Continue oral isosorbide dinitrate using an eccentric dosing schedule (e.g., 7 AM, 12 PM, 5 PM) to maintain a 14-hour nitrate-free interval and prevent tolerance 4, 6
2. Monitor blood pressure before each dose for the first 48–72 hours, then at least daily 4
3. Ensure beta-blocker therapy is initiated within 24 hours (Class I, Level B)—nitrate decisions must not delay mortality-reducing therapies 1, 4
4. Start ACE inhibitor within 24 hours if LVEF ≤0.40 or pulmonary congestion present 1

If transitioning from IV to oral nitrates:

• Administer the first oral dose 1–2 hours before discontinuing IV nitroglycerin to ensure therapeutic overlap 4
• Taper IV nitroglycerin by 5–10 mcg/min every 3–5 minutes while monitoring for rebound ischemia 4
• Do not begin tapering until the patient is symptom-free for 12–24 hours 4

Common Pitfalls to Avoid

Do not confuse nitrate use with NSAIDs: NSAIDs (except aspirin) must be discontinued at NSTEMI presentation due to increased mortality, reinfarction, heart failure, and myocardial rupture risk (Class I recommendation) 1, 2

Tolerance develops rapidly with continuous nitrate exposure: Studies demonstrate that four-times-daily isosorbide dinitrate dosing produces tolerance within days, with anti-ischemic effects lasting only 2 hours instead of 8 hours 7. A mandatory 14-hour nitrate-free interval prevents tolerance 4, 6

The FDA label warning about oral isosorbide dinitrate in acute MI refers to immediate-release formulations used as primary therapy without hemodynamic monitoring 3. This does not contraindicate guideline-directed nitrate use as part of comprehensive NSTEMI management with appropriate monitoring 1

Abrupt nitrate cessation can precipitate rebound ischemia: ECG changes may worsen when nitrates are suddenly stopped, so gradual dose reduction is essential 1, 4

Integration with Mortality-Reducing Therapies

Nitrate therapy is adjunctive for symptom control and must not replace proven mortality-reducing interventions:

• Beta-blockers (Class I, Level B) 1
• ACE inhibitors for LVEF ≤0.40 or pulmonary congestion (Class I, Level A) 1
• High-intensity statin therapy (Class I, Level A) 1
• Dual antiplatelet therapy with aspirin and P2Y12 inhibitor 2

The ACC/AHA guidelines explicitly state that nitrate dosing decisions should not preclude use of beta-blockers or ACE inhibitors 1, 4