Coronary heart disease, acute coronary syndrome, impaired glucose tolerance, type 2 diabetes mellitus Circulatory System Chronic ischaemic heart disease
Conditions
Interventions
Current interventions as of 01/08/2017:
Acarbose (oral) vs placebo
The participants in the intervention group were given one tablet (50 mg) of acarbose per day to be taken with a meal during the firs
100 mg/day), and then three tablets/day (50 mg three times a day
150 mg/day) thereafter. The maximum tolerated dose was taken for the duration of the trial (maximum dose is 150 mg/day).
Total duration of interventions
Median duration of 3.0 years
Previous interve
150 mg/day) thereafter. The maximum tolerated dose will be taken for the duration of the trial (maximum dose is 150 mg/day).
Total duration of interventions: Approximately 4 years
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 31/07/2017: 1. Male or female, aged 50 years or more 2. Definite CHD, defined as a, b or c below: a) Previous myocardial infarction (MI), or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following: i) Typical clinical presentation ii) Confirmatory ECG changes iii) Appropriate elevation of cardiac enzymes/biomarkers If original reports are unavailable then alternative documentation e.g. discharge summary or a clinical note from the study Investigator describing the evidence for a previous MI will be accepted. Note: Patients with stents are eligible. b) Previous unstable angina (UA) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following: i) Typical clinical presentation ii) Confirmatory ECG changes iii) 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. c) Current stable angina defined as: i) Typical clinical history with symptoms occurring within the last month, and ii) 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. Impaired glucose tolerance diagnosed on a single standard OGTT, defined as a 2- hour plasma glucose (2HPG) value =7.8 but 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. 2.3. Current stable angina defined as: 2.3.1. Typical clinical history with symptoms occurring within the last month, and 2.3.2. 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. Impaired glucose tolerance diagnosed on a single standard 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. 4. Optimised cardiovascular drug therapy 5. At least 80% adherent to single blind placebo Study Medication
Exclusion criteria
Exclusion criteria: Current information as of 01/08/2017: 1. Previous history of diabetes, other than gestational diabetes. 2. MI, unstable angina, stroke or a transient ischaemic attack (TIA) within the previous three months. 3. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention, at the time of randomisation. 4. NYHA class III or IV heart failure. 5. Evidence of severe hepatic disease. 6. Evidence of severe renal impairment or an eGFR <30 ml/min/1.73m2 (derived using the MDRD Chinese equation). 7. 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. 8. Pregnancy (or planned pregnancy within the next five years). 9. 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. 10. Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems. 11. Thought by the investigator for any reason to be unsuitable for participation in this clinical study. previous exclusion criteria as of 02/03/10: 1. Previous history of diabetes, other than gestational diabetes. 2. MI, unstable angina, stroke or a transient ischaemic attack (TIA) within the previous three months. 3. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention. 4. New York Heart Association (NYHA) class III or IV heart failure. 5. Evidence of severe hepatic disease. 6. Evidence of severe renal impairment or an eGFR <30 ml/min/1.73m2 (derived using the MDRD Chinese equation) 7. 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. 8. Pregnancy (or planned pregnancy within the next five years). 9. Concurrent participation in any other clinical interventional trial. Added 14/06/2017: 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. 10. Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems. 11. Thought by the investigator for any reason to be unsuitable for participation in this clinical study. Initial information at time of registration: 1. Previous history of diabetes, other than gestational diabetes 2. MI, stroke or a transient ischaemic attack (TIA) within the previous three months 3. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention 4. New York Heart Association (NYHA) class III or IV heart failure 5. Evidence of severe hepatic disease 6. Evidence of severe renal impairment or an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m^2 (derived using the MDRD Chinese equation) 7. 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 8. Pregnancy (or planned pregnancy within the next five years) 9. Concurrent participation in any other clinical interventional trial 10. Known i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 20/04/2018: Major cardiovascular events (defined as: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalisation for unstable angina or hospitalisation for heart failure [MACE5]) occurring after randomisation (baseline) were identified through patient interviews at study visits, physician and/or family member reports and by searches of local or national electronic health records, death registries, or other publicly available sources (where permitted by local ethics approvals). All events were adjudicated by an independent Clinical Events Committee, blinded to therapy allocation. Previous primary outcome measures as of 01/08/2017: A composite cardiovascular outcome defined as the time after randomization to the first occurrence of any one of the following: 1. Cardiovascular death 2. Non-fatal MI 3. Non-fatal stroke 4. Hospitalisation for unstable angina 5. Hospitalisation for heart failure Previous primary outcome measures: Occurrence of any one of the following: 1. Cardiovascular death 2. Non-fatal MI 3. Non-fatal stroke The primary and secondary outcomes will be monitored for a minimum of 4 years/participant. The outcomes will be assessed at 1, 2 and 4 months post-randomisation, and then every 4 months thereafter for the remainder of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 20/04/2018: 1. Individual MACE5 components and all-cause mortality were ascertained as for the primary outcome measure. 2. Transition to type 2 diabetes was ascertained from four-monthly study visit fasting plasma glucose values and by annual study visit 75g oral glucose tolerance tests, or by non-study physician reports adjudicated by an independent Clinical Events Committee, blinded to therapy allocation. 3. Transition to impaired renal function (defined as: eGFR =7.0 mmol/l and/or 2HPG >=11.1 mmol/l), with no intervening non-diagnostic values 2. All cause mortality 3. Composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke, hospitalisation for heart failure or hospitalisation for unstable angina. Each of the components of this composite will also be analysed individually, both as first and as total events. 4. Proportion of patients with evidence of non-alcoholic fatty liver disease (NAFLD) as judged by changes in alanine aminotransferase (ALT) levels 5. Proportion of patients with an impaired renal function as evidenced by a reduced eGFR (<60 ml/minute/1.73 m^2) estimated using the Chinese MDRD formula, or a doubling of the baseline plasma creatinine level The primary and secondary outcomes will be monitored for a minimum of 4 years/participant. The outcomes will be assessed at 1, 2 and 4 months post-randomisation, and then every 4 months thereafter for the remainder of the trial. | — |
Countries
China, England, United Kingdom
Outcome results
None listed