Baseline characteristics and temporal differences in Acarbose Cardiovascular Evaluation (ACE) trial participants

Abstract

The ACE trial is examining whether acarbose, an insulin-sparing postprandial glucose-lowering agent, can reduce cardiovascular (CV) events in patients who have coronary heart disease (CHD) and impaired glucose tolerance (IGT), with prevention of type 2 diabetes (T2D) as a secondary outcome.1,2 This update report evaluates the impact of the protocol-driven 4-week CV risk management optimization strategy during the run-in period, lists participant baseline characteristics, and examines whether temporal differences occurred during the 7-year recruitment period.Materials and methods Design The ACE trial is a randomized, double-blind, placebo-controlled, secondary-prevention study evaluating whether acarbose, added to fully optimized usual care for CV disease, is superior to placebo with respect to CV outcomes in participants who have CHD and IGT.Mean (SD) age was 64.2 (8.1) years; body mass index (BMI), 25.4 (3.1) kg/m2; systolic blood pressure, 130 (14) mm Hg; diastolic blood pressure, 78 (9) mm Hg; HbA1c, 5.9% (0.7%); low-density lipoprotein (LDL) cholesterol, 2.3 (0.8) mmol/L; and geometric mean (±1SD) triglycerides, 1.40 (0.53; 3.72) mmol/L.Fewer participants remained smokers or continued consuming alcohol, and there were statistically significant lower mean values for BMI, systolic blood pressure, diastolic blood pressure, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.Temporal differences in baseline characteristics Table III lists key baseline characteristics at enrollment by each calendar year from 2009 to 2015.N=6526 Age (y) 64.2±8.1 Male 4764 (73.0%) Current smoker 812 (12.6%) Consuming alcohol 597 (9.3%) Race Han 6331 (97.0%) Hui 74 (1.1%) Asian or Asian British 15 (0.2%) Mongolian 13 (0.2%) Wei 7 (0.11%) Miao 3 (0.05%) Tibetan 1 (0.02%) White 1 (0.02%) Other 81 (1.2%) BMI (kg/m2) 25.4±3.1 Waist circumference (cm)⁎ 91 (85, 97) Systolic blood pressure (mm Hg) 130 (14) Diastolic blood pressure (mm Hg 78 (9) Fasting plasma glucose (mmol/L) 5.4 (5.0, 5.9) 2-h plasma glucose (mmol/L) 9.1 (8.3, 10.1) HbA1c (%) 5.9±0.7 HbA1c (mmol/mol) 41±8 LDL cholesterol (mmol/L) 2.3 (0.8) HDL cholesterol (mmol/L) 1.18 (0.31) Triglycerides (mmol/L)† 1.40 (0.53, 3.72) Plasma creatinine (μmol/L) 77 (66, 89) Plasma alanine aminotransferase (U/L) 22 (17, 31) Hemoglobin (g/dL) 14.0±1.8 Mean red cell corpuscular volume (fL) 91.2±7.7 White blood cell count (×109/L) 6.3±1.8 Platelet count (×109/L) 199±58 eGFR (mL/min per 1.73 m2)⁎ 89 (75, 103) Male 89 (76, 104) Female 86 (71, 101) eGFR ≥90 3085 (47.3%) eGFR 60-89 2956 (45.3%) eGFR <60 482 (7.4%) CV risk factors Previous MI 685 (10.5%) Unstable angina 948 (14.5%) Current stable angina 727 (11.1%) Hypertension 4277 (65.5%) Previous stroke 428 (6.6%) Atrial fibrillation 255 (3.9%) Previous heart failure 243 (3.7%) Table I ACE participant baseline characteristics N=6526 At recruitment At randomization Difference P⁎ Lipid-lowering therapy Statin 91.3% 93.2% +1.9% <.0001 Fibrate 1.0% 1.0% 0% .86 Niacin 0.3% 0.3% 0% .75 Antithrombotic therapy Acetylsalicylic acid 93.2% 94.1% +0.9% .026 Clopidogrel 64.1% 61.1% −3.0% .0002 Other 1.3% 1.2% −0.1% .39 Antihypertensive therapy β-Blocker 66.0% 66.0% 0% .95 Angiotensin-converting enzyme inhibitor (ACEi) 34.5% 34.8% +0.3% .64 Angiotensin receptor blocker (ARB) 24.9% 25.8% +0.9% .25 ACEi or ARB 58.1% 59.1% +1.0% .22 Aldosterone antagonist 3.3% 2.6% −0.7% .029 Calcium-channel blocker 29.4% 29.1% −0.3% .74 Thiazide diuretic 3.2% 2.9% −0.3% .37 Nonthiazide diuretic 2.7% 2.2% −0.5% .06 Other 2.5% 1.5% −1.0% <.0001 Antianginal therapy Nitrates 38.8% 37.1% −1.7% .038 Other 6.6% 5.5% −1.1% .0042 Other CV therapy Digitalis 1.4% 1.1% −0.3% .088 Antiarrhythmics 1.6% 1.5% −0.1% .36 Glucose-lowering therapy Metformin 0.3% 0.3% 0% .75 Other <0.1% <0.1% 0% – CV risk factor values Current smoker 14.0% 12.6% −1.4% <.0001 Consuming alcohol 11.4% 9.3% −2.1% <.0001 BMI (kg/m2) 25.5 (3.1) 25.4 (3.1) −0.072 <.0001 Systolic blood pressure (mm Hg) 131 (16) 130 (14) −1.52 <.0001 Diastolic blood pressure (mm Hg) 79 (10) 78 (9) −0.43 .0003 LDL cholesterol (mmol/L) 2.4 (0.9) 2.3 (0.8) −0.12 <.0001 HDL cholesterol (mmol/L) 1.17 (0.33) 1.18 (0.31) +0.021 .0002 Triglycerides (mmol/L)† 1.45 (0.52, 3.99) 1.40 (0.53, 3.72) −0.041 .0002 Table II Cardiovascular risk factor management therapies and risk factor values, before and after the 4-week single-blind placebo run-in period 2009(n=474) 2010(n=1475) 2011(n=1787) 2012(n=1194) 2013(n=782) 2014(n=428) 2015(n=382) Women⁎ 22.4% 24.8% 27.9% 28.0% 30.1% 25.2% 29.6% Han race 97.9% 97.2% 97.2% 96.9% 97.2% 95.6% 96.1% Current smoker 13.3% 12.3% 12.2% 10.4% 13.9% 13.8% 14.2% Lipid-lowering therapy 92.6% 93.2% 94.3% 94.6% 92.3% 91.9% 93.6% ACE or ARB therapy⁎ 62.4% 61.8% 60.3% 58.2% 58.4% 50.9% 51.2% β-Blocker therapy⁎ 72.6% 67.7% 66.8% 65.2% 62.4% 61.3% 62.1% Calcium-channel blocker therapy⁎ 34.0% 30.6% 30.4% 27.5% 25.9% 28.5% 25.6% Antiplatelet therapy 98.5% 98.6% 98.4% 97.9% 96.6% 96.9% 96.8% BMI (kg/m2) 25.6 (23.7, 27.7) 25.4 (23.5, 27.3) 25.1 (23.1, 27.1) 25.1 (23.3, 27.3) 25.4 23.4, 27.5) 25.4 (23.5, 27.3) 25.3 (23.4, 27.6) HbA1c (%) 5.8 (5.5, 6.2) 5.9 (5.6, 6.3) 5.9 (5.6, 6.3) 5.9 (5.5, 6.2) 5.9 (5.6, 6.2) 5.9 (5.6, 6.2) 5.9 (5.7, 6.2) Systolic blood pressure (mm Hg) 130 (120, 140) 130 (120, 140) 130 (120, 140) 130 (120, 40) 130 (120, 140) 130 (120, 140) 130 (120, 140) LDL cholesterol (mmol/L) 2.3 (1.8, 2.8) 2.2 (1.8, 2.8) 2.1 (1.7, 2.7) 2.1 (1.7, 2.6) 2.1 (1.6, 2.8) 2.1 (1.7, 2.8) 2.1 (1.7, 2.6) eGFR (mL/min per 1.73 m2) 89 (74, 104) 88 (74, 102) 87 (74, 102) 89 (75, 103) 90 (76, 105) 90 (77, 105) 90 (75, 104) Table III Temporal changes in key baseline characteristics for participants randomized within each calendar year STOP-NIDDM4,5 DREAM6 NAVIGATOR7,8 ORIGIN9 Full cohort (N=1368) Full cohort (N=5269) Secondary prevention cohort (N=2266) Nondiabetic cohort (N=1456) Glucose-lowering Intervention Acarbose 100 mg tds Rosiglitazone 8 mg/d Nateglinide 60 mg tds Insulin glargine Entry criteria IGT IGT or IFG without known CV disease IGT and age >50 y with a prior CV event IGT or IFG with a prior CV event Male 49.0% 40.8% 69.8% 65.2% White race 97.5% 53.6% 86.5% 64.8% Age (y) 54.5 (7.9) 54.7 (10.9) 64 (57, 70) 63.5 (7.8) BMI (kg/m2) 31.0 (4.3) 30.9 (5.6) 29.76 (26.8, 33.5) 29.8 (5.2) Fasting plasma glucose (mmol/L) 6.2 (0.5) 5.8 (0.7) 6.10 (5.7, 6.5) 6.9 (6.1, 8.2) 2-h plasma glucose (mmol/L) 9.3 (1.0) 8.7 (1.4) 9.10 (8.4, 9.9) N/A Systolic blood pressure (mm Hg) 131.1 (16.3) 136.1 (18.4) 136.5 (124, 149) 146 (124, 168) LDL cholesterol (mmol/L) 3.6 (0.9) N/A 2.84 (2.29, 3.52) 2.92 (1.88, 3.96) Triglycerides (mmol/L) 2.07 (1.2) N/A 1.73 (1.23, 2.39) 1.58 (0.65, 2.23) Median follow-up for study (y) 3.3 3.0 5.0 6.2 Relative impact on risk of new-onset diabetes −25% (P=.0015) −62% (P<.0001) +7% (P=.05) −28% (P=.006) Relative impact on CV risk⁎ 49% (P=.03) +37% (P= .08) Core CV: −6% (P=.43) Extended CV: −7% (P=.16) Core CV: +2% (P=.63) Extended CV: +4% (P=.27) Table IV Cardiovascular outcome trials conducted in people with IGT, showing data only for glucose-lowering interventions