Acarbose Cardiovascular Evaluation Trial (ACE)

• Transition to type 2 diabetes [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• All cause mortality [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Cardiovascular death, non-fatal MI, non-fatal stroke, hospitalization for heart failure or hospitalization for unstable angina. [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Evidence of NAFLD [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Impaired renal function [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Resource use, costs and cost effectiveness [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]

• Transition to type 2 diabetes [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• All cause mortality [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Cardiovascular death, non-fatal MI, non-fatal stroke, hospitalization for heart failure or hospitalization for unstable angina. [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Evidence of NAFLD [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]
• Impaired renal function [ Time Frame: Follow-up for approximately 4 years until 904 adjudicated Primary Outcome Measures have been recorded. ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether acarbose therapy can reduce cardiovascular-related morbidity and mortality in patients with impaired glucose tolerance (IGT) who have established coronary heart disease (CHD) or acute coronary syndrome (ACS). A secondary objective of the study is to determine if acarbose therapy can prevent or delay transition to type 2 diabetes mellitus (T2DM) in this patient population.

A 4-year, multi-centre, double-blind, randomised parallel-group trial to determine whether reducing post-prandial glycaemia can reduce cardiovascular-related morbidity in patients with established coronary heart disease or acute coronary syndrome who have impaired glucose tolerance.

• Coronary Heart Disease
• Acute Coronary Syndrome
• Impaired Glucose Tolerance
• Type 2 Diabetes Mellitus (T2DM)

• Drug: Acarbose
  The participants will be given one tablet (50mg) of acarbose per day to be taken with a meal during their first week (7 days). During the second week, the dose is increased to two tablets/day (50mg twice a day i.e. 100mg/day) and then three tablets/day (50mg three times a day i.e. 150mg/day) thereafter. The maximum tolerated dose will be taken for the duration of the trial (maximum dose is 150mg/day).
  Other Name: Glucobay
• Drug: Matching Placebo
  The participants will be given one tablet of matching placebo per day to be taken with a meal during their first week (7 days). During the second week, the dose is increased to two tablets/day and then three tablets/day thereafter. The maximum tolerated dose will be taken for the duration of the trial (maximum dose is 3 tablets/day).

• Active Comparator: Acarbose
  Intervention: Drug: Acarbose
• Placebo Comparator: Matching Placebo
  Intervention: Drug: Matching Placebo

Inclusion Criteria:

• Male or female, aged 50 years or more.

• Definite CHD, defined as a, b or c below:

  1. Previous myocardial infarction (MI) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following (Note: Patients with stents are eligible):

     • Typical clinical presentation
     • Confirmatory ECG changes
     • Appropriate elevation of cardiac enzymes/biomarkers

  2. 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.

  3. 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 75g anhydrous glucose 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.
• 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 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.
• 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.