24th April 2024

Angina and Acute Coronary Syndrome

Angina

Stable angina is defined as a typical triad of constricting chest, jaw or arm discomfort precipitated by physical exertion and relieved by rest or glyceryl trinitrate (GTN) spray within approximately five minutes. It is the result of myocardial ischaemia, commonly due to atherosclerotic obstructive coronary artery disease (CAD), which restricts blood flow and oxygen delivery to the heart muscle. Other causes include coronary spasm, aortic valve disease, oesophageal spasm and anaemia. The prevalence of angina increases with age and is higher in males, with 12-14% of males aged 65-84 years having the diagnosis. Complications include unstable angina, myocardial infarction, stroke, and sudden cardiac death.

Management

Angina management aims to reduce or prevent symptoms, improve quality of life and long-term morbidity and mortality. This includes lifestyle advice, drug treatment and revascularisation. 

Acute attacks are managed with a short-acting nitrate such as sublingual GTN spray which can also be used as prevention before performing activities which are known to bring on an attack. Anti-anginal drug therapies prevent episodes of angina and include monotherapy with cardio-selective beta blockers (bisoprolol, atenolol, metoprolol, nebivolol) or rate-limiting calcium channel blockers (verapamil, diltiazem). If either monotherapy is not tolerated, a trial of the other should be considered. Where symptoms persist, a combination of beta blocker and a dihydropyridine calcium channel blocker (modified-release nifedipine, amlodipine, felodipine) can be tried. 

If both beta and calcium channel blockers are not tolerated or contraindicated, monotherapy with one of the following is considered:

• Long-acting nitrate isosorbide mononitrate (ISMN) or isosorbide dinitrate (ISDN)
• Funny channel (lf) inhibitor ivabradine
• Potassium channel activator nicorandil 
• Late inward sodium current inhibitor ranolazine. 

If symptoms remain despite beta blockade or calcium channel blocker monotherapy, and using the other is contraindicated or not tolerated, an additional drug from ISMN, ISDN, ivabradine, nicorandil or ranolazine can be added. 

Where optimal medical management fails ie., symptoms persist despite a combination of two drugs titrated to maximum dose, patients should be referred for consideration of revascularisation through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). A third anti-anginal is considered in symptomatic patients who are waiting for revascularisation therapy or where revascularisation is not appropriate. 

Unless there is a contraindication, aspirin and statin therapy is recommended as secondary prevention for patients with angina. 

Nitrates

Short-acting GTN used for immediate relief of angina is available in tablet or sublingual spray form. Long-acting oral nitrates decrease the frequency and severity of anginal symptoms and are available in standard and modified-release preparations. With standard preparations, asymmetric dosing intervals are used to keep a nitrate-free time of 10-14 hours to reduce the development of tolerance. Modified-release preparations are taken once daily. 

Nitrates are converted to nitric oxide (NO), which is typically depleted in diseases such as atherosclerosis. Activation of guanylate cyclase increases intracellular cyclic guanosine monophosphate (cGMP) levels and reduces intracellular calcium levels. The reduction in calcium results in smooth muscle relaxation and coronary vessel dilatation, improving myocardial oxygen supply. Dilation of peripheral veins reduces preload and afterload, in turn reducing myocardial workload and oxygen demand. 

Side effects of nitrates include hypotension, headache and flushing. These can be minimised by starting at a low dose and titrating up. Medications such as phosphodiesterase inhibitors should be avoided with nitrates as the risk of excessive hypotension may precipitate myocardial infarction. 

Acute Coronary Syndrome  

Acute coronary syndrome (ACS) is a spectrum including STEMI, NSTEMI and unstable angina. STEMI results from complete and persistent blockage of one or more of the coronary arteries, resulting in myocardial necrosis. NSTEMI occurs as a result of partial or intermittent coronary artery blockage. In unstable angina, there is partial or intermittent blockage without necrosis. NSTEMI is distinguished from unstable angina by raised troponin, which is not seen in unstable angina.

Management

Initial pharmacological management is with a loading dose of aspirin 300mg, GTN spray and analgesia such as intravenous opiates with antiemetic cover. Oxygen is not recommended where saturation is >94%. 

Close monitoring of blood glucose is essential and variable rate insulin infusion should be considered where glucose trends above 11 mmol/litre. 

STEMI

Patients with STEMI, presenting within 12 hours of symptom onset, are candidates for primary PCI (PPCI) but may still be considered up to 48 hours after onset if there is ongoing pain with evidence of myocardial ischaemia or cardiogenic shock. 

Unless there is a contraindication to long term dual antiplatelet therapy (DAPT), drug-eluting stents (DES) are used over bare metal stents for PCI and DAPT is continued for 12 months after PCI. Complications of stents include stent thrombosis and in-stent restenosis. The risk of in-stent restenosis is minimised by DES through regulated elution of antimitotic drugs: sirolimus or paclitaxel. 

Prasugrel is preferred as the second antiplatelet with aspirin after PPCI or ticagrelor if the bleeding risk is high. Clopidogrel is used with aspirin if the patient is established on anticoagulation for a separate indication.

The choice of antithrombin therapy is guided by the access site used for coronary angiography (CAG) and the patient’s renal function. Options include unfractionated heparin, glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin.  

STEMI patients presenting within 12 hours of symptom onset but where PCI cannot be delivered in 120 minutes are candidates for fibrinolysis with a thrombolytic such as alteplase, following which an ECG is repeated 60-90 minutes after to assess for resolution of ST segment elevation. CAG with PCI is indicated if there is >50% residual ST-segment elevation following fibrinolysis. 

Fibrinolytic therapy is contraindicated in patients with recent haemorrhage or prior intracerebral haemorrhage, recent surgery, ischaemic stroke within three months, aortic dissection and known structural cerebrovascular lesions including neoplasms. 

NSTEMI and Unstable Angina

Unless there is a high bleeding risk or immediate CAG is expected, fondaparinux is the initial choice of antithrombin. In renal impairment unfractionated heparin is an alternative and requires monitoring of the activated partial thromboplastin time (aPTT). Ticagrelor is used as the second antiplatelet with aspirin unless the patient is established on oral anticoagulation where clopidogrel is used with aspirin.

Secondary prevention 

In addition to a cardiac rehabilitation programme and lifestyle advice, the following medications are indicated for secondary prevention:

• ACE inhibitors (ramipril, enalapril) to be continued indefinitely 
• Dual antiplatelet therapy for 12 months, then lifelong aspirin
• Cardio-selective beta blocker aiming for a heart rate < 70 beats per minute. If contraindicated or intolerant to beta blockers and there is no evidence of heart failure, non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are an alternative. 
• Statins (rosuvastatin, atorvastatin) – doses in secondary prevention differ from primary prevention, e.g., atorvastatin is 20mg once nightly compared to 80mg once nightly when used as secondary prevention.
• Aldosterone antagonists (eplerenone, spironolactone) for heart failure with reduced left ventricular ejection fraction 

References 

• The British Journal of Cardiology. Angina Module 1: Epidemiology. Available from https://bjcardio.co.uk/2020/04/angina-module-1-epidemiology-2/ Accessed February 1 2024.
• NICE. Stable Angina: Management. Available from https://www.nice.org.uk/guidance/cg126 Accessed February 1 2024.
• NICE. Acute Coronary Syndromes. Available from: https://www.nice.org.uk/guidance/ng185 Accessed February 1 2024.