Acarbose Cardiovascular Evaluation Trial

A long-term, multicentre, double-blind, randomised parallel-group trial to determine whether reducing post-prandial glycaemia can reduce cardiovascular-related morbidity and mortality in patients with established coronary heart disease or acute coronary syndrome who have impaired glucose tolerance.

Inclusion criteria

• Male or female, aged 50 years or more.
• Definite CHD, defined as a, b or c below:

• Previous myocardial infarction (MI) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following:

• Typical clinical presentation
• Confirmatory ECG changes
• Appropriate elevation of cardiac enzymes/biomarkers
• Previous unstable angina (UA) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following:

• Typical clinical presentation
• Confirmatory ECG changes
• Either elevation of a cardiac biomarker or a >50% stenosis in ≥1 major epicardial coronary artery shown on coronary angiography or CT angiography. Where stenosis is reported in a qualitative manner, the categories "moderate" and "severe" will be taken as equating to >50% stenosis.
• Current stable angina defined as:

• Typical clinical history with symptoms occurring within the last month, and
• A >50% stenosis in ≥1 major epicardial coronary artery shown on coronary angiography or CT angiography. Where stenosis is reported in a qualitative manner, the categories "moderate" and "severe" will be taken as equating to >50% stenosis.
• Impaired glucose tolerance diagnosed on a single standard oral glucose tolerance test (OGTT) , defined as a 2-hour plasma glucose (2HPG) value ≥7.8 but <11.1 mmol/l and a fasting plasma glucose (FPG) <7.0 mmol/l within six months prior to enrollment.
• Optimised cardiovascular drug therapy.
• At least 80% adherent to single blind placebo Study Medication during the run-in period.
• Provision of written informed consent.

Exclusion criteria

• Previous history of diabetes, other than gestational diabetes.
• MI, unstable angina, stroke or a transient ischaemic attack (TIA) within the previous three months.
• Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention, at the time of randomisation
• New York Heart Association (NYHA) class III or IV heart failure.
• Evidence of severe hepatic disease.
• Evidence of severe renal impairment or an eGFR <30 ml/min/1.73m2 (derived using the Modification of Diet in Renal Disease, MDRD, Chinese equation)
• Any other condition likely to reduce adherence to the protocol e.g. alcoholism, major active psychiatric disorder, cognitive impairment or a condition likely to markedly limit life expectancy e.g. malignancy.
• Pregnancy (or planned pregnancy within the next five years).
• Concurrent participation in any other clinical interventional trial. Note: Patients who were treated previously with an alphaglucosidase inhibitor must have at least a three-month washout period before being randomised into the ACE trial.
• Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems.
• Thought by the investigator for any reason to be unsuitable for participation in this clinical study.