Guidance on the use of glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes

Coronary heart disease (CHD) is the most common cause of death in the UK. It is a progressive disease. The first presenting symptom is often stable angina (pain in the chest on exertion), which may progress to an acute coronary syndrome (ACS). ACSs encompass a range of symptoms with broadly similar underlying causes. They include ischaemic cardiac chest pain of recent origin in the categories:

• non-ST-segment-elevation ACS, including unstable angina and non-ST-segment-elevation myocardial infarction (NSTEMI)

• myocardial infarction (MI) with ST-segment-elevation (an acute MI, also known as STEMI).

Unstable angina covers a range of clinical states falling between stable angina and acute MI, including angina at rest lasting more than 20 minutes, increasing angina and angina occurring more than 24 hours after an acute MI.

NSTEMI (also known as non-Q-wave MI) is the term used when the cardiac markers (troponins and creatine kinase [CK]) are elevated to ranges that indicate that MI has occurred, but a Q-wave does not develop on ECG tracings. This profile is thought to indicate damage to the heart muscle that does not extend through the full thickness of the myocardium. NSTEMI therefore represents a subgroup of patients with non-ST-elevation ACS at high risk of a subsequent event.

In 1998, the overall prevalence of CHD in England was estimated to be 7.1% in men and 4.6% in women. Prevalence increases with age. It is difficult to estimate the incidence of ACS in England and Wales. The hospital episode statistics for 2000/01 detail 148,000 episodes of angina pectoris in England, with 83,000 of these specified as unstable angina. However, there are variations in the coding of this condition, and it has been suggested that these figures are conservative. Recently, the incidence of unstable angina has been estimated at 226 cases per 100,000 population, which equates to approximately 120,000 cases in England and Wales per annum.

In 1999, in England and Wales, there were over 115,000 deaths caused by CHD. Although CHD-associated mortality rates are falling by about 4% per year in the UK, this does not reflect a fall in incidence of the disease. In addition, improvements in rates of death from CHD have not been uniform across all social classes; death rates among unskilled men are 3 times greater than those among professional men.

The main aim in the short-term management of non-ST-segment-elevation ACS is to control pain and prevent progression to full-thickness MI (STEMI) and/or death. The first steps in the management pathway involve bed rest and medical treatment including antiplatelet therapy (aspirin), anticoagulants (heparin and low-molecular-weight heparin [LMWH]), vasodilators (nitrates), calcium-channel blockers and beta-blockers. Revascularisation, when necessary, is by means of PCI, usually with stent implantation, or by CABG.

Certain patients with unstable angina are at high risk of progression to MI or death. The British Cardiac Society guidelines say that certain circumstances are associated with an increased risk of early adverse outcome, including age above 65 years; comorbidity, especially diabetes; prolonged (more than 15 minutes) cardiac pain at rest; ischaemic ECG ST-segment depression on admission or during symptoms; ECG T-wave inversion (associated with an intermediate risk, lying between that associated with ST-segment depression and normal ECG); evidence of impairment of left ventricular function (either pre-existing or during MI); and elevated C-reactive protein. In addition, those with raised levels of cardiac troponin are considered to be at high risk of an event.

Despite the use of standard therapy (antiplatelet agents and anticoagulants), the rate of adverse outcomes (such as death, non-fatal re-infarction, refractory angina or readmission for unstable angina) at 6 months after presenting with unstable angina is about 30%.

In guidance issued in September 2000, NICE recommended the intravenous use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, in addition to aspirin and low (adjusted) dose unfractionated heparin, for patients with unstable angina at high risk of death or further MI. NICE's guidance recommended intravenous administration of GP IIb/IIIa inhibitors to patients undergoing acute or elective PCI.