Organic nitrates
| Type | Recommendation |
|---|---|
| When to deprescribe | |
| CBR |
We suggest deprescribing decisions be made in consultation with the individual and their GP and/or specialist providers to ensure it aligns with their preferences, goals and overall treatment plans. We suggest deprescribing be offered to older people taking long-acting nitrates in combination with beta-blockers or calcium channel blockers for stable coronary heart diseases who have not experienced angina symptoms or have not required short-acting nitrates for at least six months. |
| Ongoing treatment | |
| CBR |
We suggest short-acting nitrates be offered to people for acute relief should angina symptoms occur. |
| CBR |
If deprescribing is unsuccessful despite one attempt, we suggest maintaining the lowest effective dose; however, we suggest reassessing the need for long-term therapy periodically. |
| How to deprescribe | |
| CBR |
In general, we suggest tapering the dosage and ensuring that short-acting nitrates are available should symptoms occur. For oral formulations, gradually reduce the dose, such as from 120mg daily to 60mg daily, to 30mg daily, then finally discontinue completely. For transdermal formulations, gradually reduce the dose, such as from 15 mg/24 hours to 10 mg/24 hours, to 5 mg/24 hours, then finally discontinue completely. If symptoms recur, we suggest restarting long-acting nitrates at the previously tolerated dose, delaying further dose reductions by an agreed interval for stabilisation, and planning for a more gradual taper if appropriate. |
| Monitoring | |
| CBR |
We suggest closely monitoring for blood pressure or recurrence of angina symptoms tailoring the approach to individual factors such as preferences, responses, and tolerance to deprescribing. If in-person visits are impractical, we suggest advising people to report symptom recurrence as needed (e.g. telehealth). |
CBR, consensus-based recommendation
Long-acting nitrates are commonly used for angina prophylaxis and are effective in increasing exercise capacity in people with stable angina. However, RCTs have not demonstrated a reduction in major adverse cardiac events (MACE) with the use of nitrates [301]. In people with stable angina, long-acting nitrates are typically prescribed to prevent angina attacks [302]. Current guidelines for the management of chronic coronary disease recommend antianginal therapy with either a beta-blocker, calcium channel blockers, or long-acting nitrate for relief of angina or equivalent symptoms [303]. The addition of a long-acting nitrate to a beta blocker or a calcium channel blocker has been shown to improve exercise tolerance and reduce the frequency of angina and use of short-acting nitrate [303].
Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).
For immediate short-term relief of angina, short-acting sublingual nitroglycerin remains the mainstay of treatment. The benefits of long-acting nitrates must be weighed against the potential adverse effects, including headache, orthostatic hypotension, rebound angina, dyspepsia, and peripheral oedema [304].
Deprescribing (de-escalation from combination therapy) may be appropriate in people taking long-acting nitrates in combination with beta-blockers or calcium channel blockers for stable coronary heart diseases who have not experienced angina symptoms or have not required short-acting nitrates for at least six months.
We identified one RCT and one non-controlled study related to long-acting nitrates deprescribing from the systematic review and meta-analysis [305, 306].
Overall, the current evidence for deprescribing long-acting nitrates is derived from a single RCT and a single-arm study of small sample sizes and low certainty. Although these studies showed that most participants with stable coronary disease were able to safely discontinue their long-term nitrates without major adverse cardiac events, the evidence is insufficient to inform evidence-based recommendations.
It may be appropriate to closely monitor for the recurrence of angina symptoms (e.g. breathlessness) and blood pressure. Current evidence indicates that most individuals who experience a recurrence of angina symptoms report it within the first month of medication withdrawal. The monitoring approach should be tailored to each individual’s needs and circumstances. It may be helpful to provide examples of common symptoms when encouraging individuals to self-monitor and report symptoms. As some symptoms are non-specific, many individuals may not recognise that they could be indicative of a worsening of the condition.
Key study characteristics and results
A narrative summary of each study is provided below, highlighting key characteristics and main findings.
George 2003 [305] conducted an RCT that reported deprescribing of long-acting nitrates in 80 participants with coronary artery disease who were angina-free and hemodynamically stable. Eight out of 80 participants (10%) in the intervention group had a recurrence of anginal symptoms within the first month of withdrawal, compared with one out of 40 (2.5%) control participants. The mean interval until the recurrence of anginal symptoms was two weeks. All eight participants responded well to the reinitiation of nitrates.
Jackson 2005 [306] reported a before-and-after study of deprescribing long-acting nitrates in 55 men with stable coronary disease and concurrent erectile dysfunction to facilitate the use of phosphodiesterase type five (PDE5) inhibitors. Concomitant beta-blocker or calcium antagonist therapy was continued following nitrate deprescribing. Three participants (5%) restarted their nitrates due to a slight increase in breathlessness. There were no adverse cardiac events or deterioration in subjective exercise ability.
Nitrates were discontinued abruptly in the RCT [305] whereas in another study, the nitrate dose was halved for two days and then discontinued if no there was no increase in symptoms [306].
Compared to abrupt cessation, dose tapering is likely more acceptable for most people and practical to determine the lowest effective dose for some people requiring dose reduction rather than complete cessation. Short-acting nitrates should be available for acute relief should angina symptoms occur.