Antianginal Medicine Selection

Antianginal medicine selection relieves symptoms and improves exercise capacity in chronic coronary syndrome, and does not by itself reduce death. Every person needs a short-acting nitrate for attacks and one or two long-acting drugs to prevent them, together with aspirin 75 mg daily, a statin and an ACE inhibitor where indicated. A beta blocker or a calcium channel blocker is the first choice, and a second drug is added when symptoms persist. Treatment is aimed at fewer than 2 attacks a week and a resting heart rate of 55 to 60 beats a minute.

Attack treatment. Glyceryl trinitrate sublingual spray 400 micrograms (1 to 2 sprays), repeated after 5 minutes to a maximum of 3 doses. Seek emergency help if pain is not relieved 5 minutes after the first dose.

Vasospastic angina. Prefer calcium channel blockers and nitrates, and avoid beta blockers.

Beta blocker. Bisoprolol 5 mg orally once daily, increased to 10 mg daily; or metoprolol succinate 50 mg once daily, increased to 200 mg daily.

Calcium channel blocker. Amlodipine 5 mg orally once daily, increased to 10 mg daily. Or diltiazem modified-release 120 mg once daily, increased to 360 mg daily (not with a beta blocker, and not in reduced ejection fraction). Or verapamil modified-release 120 to 240 mg daily.

Combination. A beta blocker with amlodipine is the usual first combination. Do not combine a beta blocker with verapamil or diltiazem.

Long-acting nitrate, second line. Isosorbide mononitrate modified-release 30 to 60 mg orally once daily in the morning, up to 120 mg. Leave a nitrate-free interval of 10 to 14 hours (asymmetric dosing) to prevent tolerance.

Other second-line drugs.

• Ivabradine 5 mg orally twice daily, increased to 7.5 mg twice daily (2.5 mg twice daily at age 75 or over), in sinus rhythm with heart rate of 70 beats a minute or over, not with verapamil or diltiazem.
• Nicorandil 10 mg twice daily, increased to 20 mg twice daily; warn of mouth and gastrointestinal ulceration.
• Ranolazine 375 mg twice daily, increased to 500 mg and then 750 mg twice daily; avoid in creatinine clearance under 30 mL/min or cirrhosis, and watch the QTc.
• Trimetazidine 35 mg modified-release twice daily, not in Parkinson disease.

Absolute interaction. Do not give any nitrate or nicorandil with a phosphodiesterase type 5 inhibitor. Wait 24 hours after sildenafil or vardenafil and 48 hours after tadalafil.

Special groups. In older adults use half starting doses and watch for postural hypotension. In asthma use amlodipine or diltiazem. In diabetes beta blockers may mask hypoglycaemia. In pregnancy use metoprolol or nifedipine, and avoid ranolazine and ivabradine. In hepatic impairment lower doses of metoprolol, diltiazem and amlodipine (amlodipine 2.5 mg start). In creatinine clearance under 30 mL/min avoid ranolazine. In East Africa, amlodipine and a generic beta blocker are available and cheap, and a nitrate spray should be prescribed for every person.

Monitoring. Attack frequency, glyceryl trinitrate use, heart rate, pressure, ankle swelling and exercise tolerance at 2 to 4 weeks after each change. Check ECG for QTc with ranolazine.

Titration. Increase every 2 weeks to the maximum tolerated dose before adding a second drug.

Nitrates. Warn of headache, flushing and postural hypotension, and advise sitting for the first dose.

Stopping. Do not stop a beta blocker suddenly. Stop nicorandil for ulceration. Stop a long-acting nitrate gradually if symptoms allow.

Common errors. Nitrate with sildenafil, a beta blocker with verapamil, no nitrate-free interval, and treating symptoms without secondary prevention.

Referral and escalation. Refer for rest angina, accelerating angina, new angina in the past month, symptoms despite two drugs, or for angiography or revascularisation.