Nitrates, Calcium-Channel Blockers and Other Anti-Anginal Drugs

NHSL Medicines Guidance
NHS Lanarkshire

Nitrates

Preferred list (P)

GLYCERYL TRINITRATE sublingual pump spray

  • For rapid symptomatic relief of angina.

ISOSORBIDE MONONITRATE modified release tablets/capsules

  • Restriction: For patients who have compliance problems OR have previously tried standard release ISOSORBIDE MONONITRATE and are intolerant to side effects such as flushing, headache and postural hypotension.

ISOSORBIDE MONONITRATE standard release tablets

Prescribing Notes:

  • Patients prescribed sublingual GTN should be advised:
    • How to use it correctly with emphasis on repeating the dose at five minute intervals for a total of three doses if required to relieve symptoms. If symptoms have not resolved after a total of three doses, the patient should dial 999.
    • To check regularly that their spray has not expired.

  • Transdermal nitrate preparations are significantly more expensive than standard formulations and not a cost-effective option.

Dihydropyridine Calcium-Channel Blockers

Preferred list (P)

AMLODIPINE

Total list (T)

FELODIPINE

Prescribing Notes:

  • All dihydropyridine calcium-channel blockers are equally effective. Choice should be based on co-morbidities, potential drug interactions and cost-effectiveness.

  • If management of hypertension or angina with a calcium-channel blocker is considered necessary in a patient with concomitant heart failure AMLODIPINE or FELODIPINE may be considered. All dihydropyridine calcium-channel blockers are contra-indicated in unstable heart failure.

  • Sudden withdrawal of calcium-channel blockers may exacerbate angina; withdraw if ischaemic pain occurs or worsens after starting treatment.

  • NIFEDIPINE
    • There is conflicting evidence on the safety of NIFEDIPINE in people with angina.
    • A meta-analysis suggests that NIFEDIPINE monotherapy or short-acting NIFEDIPINE in combination with other drugs for angina may increase the risk of cardiovascular events (Stason et al., 1999 DOI: https://doi.org/10.1161/01.HYP.33.1.24).
      However, long-acting NIFEDIPINE is safe and reduces the need for coronary angiography and cardiovascular interventions.
    • Meta-analyses have indicated that NIFEDIPINE monotherapy or short-acting NIFEDIPINE in combination with other anti-anginal drugs may increase the incidence of cardiovascular events, mainly angina episodes (Montalescot et al., 2013 DOI: https://doi-org.knowledge.idm.oclc.org/10.1093/eurheartj/eht296).

Rate-Limiting Calcium-Channel Blockers

Preferred list (P)

VERAPAMIL

  • Use of VERAPAMIL in combination with a beta-blocker should be avoided due to risk of severe bradycardia or AV block.

 

Total list (T)

DILTIAZEM

  • Restriction: For patients in whom VERAPAMIL is contra-indicated, not tolerated or who are co-prescribed a beta-blocker.

  • Brand prescribing is recommended for modified-release preparations containing more than 60 mg diltiazem hydrochloride.
    Currently ZEMTARD XL® is the most cost-effective brand within Primary Care.

Prescribing Notes:

  • When a beta-blocker is contra-indicated or not tolerated a rate limiting calcium channel blocker is preferred to a dihydropyridine calcium channel blocker for the management of angina as they have the added effect of decreasing myocardial contractility and heart rate.

  • DILTIAZEM is first choice calcium-channel blocker for angina if a beta–blocker cannot be used; can also be given for hypertension.

  • VERAPAMIL should NOT be used in combination with beta-blockers due to the risk of cardiac depression. Diltiazem may be considered for use in combination with beta-blockers, but caution should be exercised and the benefits versus the risks of co-prescribing carefully considered.

  • Refer to Class 2 Anti-Arrhythmics for NHS Lanarkshire recommendations on choice of beta-blocker in the management of arrhythmias.

Potassium-Channel Activator Drugs

Preferred list (P)

NICORANDIL

Selective Sinus Node I(f) Inhibitors

Specialist initiation (S1)

IVABRADINE

  • SMC Restriction:
    • For symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm for whom heart rate control is desirable and who have a contra-indication or intolerance to beta-blockers and rate-limiting calcium channel blockers.
    • For use in accordance with its licensed indication for heart failure ONLY if resting heart rate remains ≥ 75 beats per minute despite optimal standard therapy. 

Prescribing Notes:

  • Should not be initiated in patient with angina if heart rate <70 beats per minute or in patients with chronic heart failure if heart rate <75 beats per minute.
  • When prescribed for the management of angina, consideration should be given to stopping treatment if there is limited or no symptom improvement after 3 months.
  • IVABRADINE has been associated with QT interval prolongation and careful consideration should be given to the risks versus the benefits of concurrent use with other drugs which may augment this effect.
  • Concurrent use with DILTIAZEM, VERAPAMIL and ERYTHROMYCIN is contra-indicated.
  • Patients taking IVABRADINE should have regular monitoring for signs and symptoms of bradycardia and atrial fibrillation. IVABRADINE should be discontinued if resting heart rate is persistently below 50 beats per minute, despite dose reduction.

NHSL Joint Adult Formulary Key

To indicate the category of a formulary medicine, updated sections adopt the following key:

Preferred list (P): First-line formulary choices.

Total list (T): Alternative choices when preferred list options not effective/not tolerated, or not indicated.

Specialist initiation (S1): Specialist initiation, or on the advice of a Consultant or Specialist Practitioner in this therapeutic area. Continuation in primary care is acceptable.

Specialist use only (S2): Supply via hospital, Homecare Service or a hospital based prescription (HBP) for dispensing by community pharmacy. Not prescribed in primary care setting.

Editorial Information

Last reviewed: 31/01/2022

Next review date: 31/01/2025

Author(s): NHSL.

Version: Please refer to the introduction section for an explanation of the review dates above.

Approved By: ADTC

Reviewer name(s): ADTC.