skip to main content

Nitrate-free Interval — EECC MCQ

Instant feedback + full explanation. One question, done properly.

EasyCoronary Artery DiseaseNitrate-free IntervalEECC

A 65-year-old man with stable angina on bisoprolol 10 mg and amlodipine 10 mg continues to have exertional symptoms. His resting HR is 55 bpm and BP 115/70. Adding a long-acting nitrate (ISMN) is considered. What is the key prescribing principle for long-acting nitrates?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: E — A nitrate-free interval of 10-14 hours per day is essential to prevent nitrate tolerance — typically achieved by asymmetric dosing (e.g. ISMN 60 mg in the morning only, or patch applied for 12-14 hours then removed)

Nitrate tolerance is a well-recognised phenomenon where continuous nitrate exposure leads to diminished vasodilatory response within 24-48 hours. The mechanism involves: depletion of sulfhydryl groups needed for nitric oxide generation, counter-regulatory neurohormonal activation, and increased superoxide production. To maintain efficacy, a nitrate-free interval of 10-14 hours/day is essential. Practical approaches: (1) ISMN modified-release: single morning dose (covers daytime angina, free interval overnight); (2) GTN patch: apply in the morning, remove at bedtime; (3) ISDN: asymmetric dosing (e.g. 8am and 2pm, no evening dose). The 2024 ESC CCS Guidelines recommend this approach (Class I). During the nitrate-free interval, rebound angina can occur — adequate background anti-anginal therapy (beta-blocker/CCB) provides coverage.

Reference: ESC (2024): CCS Guidelines