Person:

Mehta, Cyrus

Aims To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE). Methods: The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double‐blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events. Results: Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (P interaction = 0.971) or HbA1c category at 1 month. Patients in the combined treatment groups (n = 5380) who experienced serious hypoglycaemia (n = 34) had higher MACE rates than those who did not (35.3% vs 11.4%, adjusted hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.27–4.60; P = .007), although the association was less strong when analysing only events after the hypoglycaemic event (adjusted HR 1.60, 95% CI 0.80, 3.20). Conclusions: There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post‐ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed.

Aims We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high‐sensitivity C‐reactive protein (hsCRP) level and low‐density lipoprotein cholesterol (LDL‐C) in patients with type 2 diabetes and recent acute coronary syndrome. Materials and methods Study participants enrolled in the EXAMINE trial (Clinical trials registration number: NCT00968708) and were stratified by baseline hsCRP levels (<1, 1‐3 and >3 mg/L). They were also sub‐divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/L) and achieved LDL‐C (<70 or ≥70 mg/dL) levels. Among 5380 patients, the MACE rate, a composite of cardiovascular death, non‐fatal acute myocardial infarction and non‐fatal stroke, was evaluated during the 30 months of follow‐up. Results: Cumulative incidence of MACE was 11.5% (119 events), 14.6% (209 events) and 18.4% (287 events) in patients with hsCRP levels of <1, 1 to 3 and >3 mg/L, respectively (P < .001). In patients with hsCRP >3 mg/L, the adjusted hazard ratio (95% confidence interval) was 1.42 (1.13, 1.78; P = .002) for MACE compared with patients with hsCRP <1 mg/L. MACE cumulative incidences were 11.0% (128 events), 14.4% (100 events), 15.6% (194 events) and 21.3% (182 events) in patients with low LDL‐C and low hsCRP, low LDL‐C and high hsCRP, high LDL‐C and low hsCRP, and high LDL‐C and high hsCRP levels, respectively (P < .001). Conclusions: Levels of hsCRP were associated with recurrent cardiovascular events in patients with type 2 diabetes and recent acute coronary syndrome, and this association appears to be independent of and additive to the achieved LDL‐C level.