Baseline HbA1c levels associated with CV outcomes in high risk T2DM patients

Impact of Baseline Glycemic Control on Residual Cardiovascular Risk in Patients With Diabetes Mellitus and High-Risk Vascular Disease Treated With Statin Therapy

Literature - Menon V, Kumar A, Patel DR et al., - J Am Heart Assoc. 2020, doi: 10.1161/JAHA.119.014328.

Introduction and methods

In the UKPDS study, an association was found between HbA1c levels and the risk of macrovascular and microvascular events in patients with T2DM [1]. However, a reduction of HbA1c with glycemic control using predominantly sulfonylurea-based pharmacotherapy showed no association with macrovascular benefits [2]. The number of pharmacotherapeutic options for treatment of T2DM that both improve glycemic control and reduce CV risk have increased in the last years [6], but it remains unclear whether HbA1c can be used as a marker of CV risk. This post-hoc analysis of the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial [3] evaluated the usefulness of HbA1c as a biomarker of CV risk in optimally treated T2DM patients with high CV risk.

The ACCELERATE trials was a randomized, double-blinded placebo-controlled trial examining the treatment of evacetrapib, a CETP inhibitor, in patients with high CVD risk. Participants were randomized in a 1:1 manner to receive evacetrapib, 130 mg, or placebo. The trial was terminated prematurely after a mean follow-up of 30 months because no overall benefits with evacetrapib were found. This subanalysis investigated the relation between baseline HbA1c (measured at study initiation) and CV events during a follow-up of 30 months in 8145 T2DM patients with a history of coronary artery disease and on optimal medical therapy. Since no effect of evacetrapib was found in the ACCELERATE trial, the entire population with DM was evaluated, regardless of treatment assignment to evacetrapib or placebo.

The primary endpoint was MACE, which included CV death, nonfatal MI, stroke, coronary revascularization, or hospitalization for unstable angina. The secondary endpoint was a composite of CV death, nonfatal MI, and stroke.

Main results

  • Increasing HbA1c levels at baseline were associated with the occurrence of MACE (Kaplan-Meier (KM) estimates for risk of MACE were 12.6, 14.5, 14.0, 16.1, 16.3, 18.2 for baseline HbA1c levels (%) of <6.0, 6.0-<6.5, 6.5-<7.0, 7.0-<7.5, 7.5-<8.0, ≥8.0, respectively, P <0.001).
  • Increasing HbA1c levels at baseline were also associated with the secondary composite endpoint of CV death, nonfatal MI, and stroke (KM estimate, 7.8-11.3, P=0.003).
  • Individual endpoints of nonfatal MI (KM estimate 3.1-7.0, P<0.001), hospitalization for unstable angina (KM estimate 1.8-5.0, P=0.003), and need for coronary revascularization (KM estimate 7.3-11.1, P=0.001) were also associated with increasing HbA1c levels at baseline.
  • HbA1c at baseline was an independent predictor for the primary endpoint censored at 915 days, when adjusted for significant baseline characteristics in a multivariable model (HR 1.06, 95%CI 1.02-1.11, P=0.003).
  • Rates of CV mortality and all-cause mortality were similar across HbA1c groups at baseline (KM estimate 2.6-4.3, P=0.21, for CV mortality and KM estimate 4.8-5.9, P=0.21, for all-cause mortality).


This subanalysis of the ACCELERATE trial showed that HbA1c levels at study baseline are associated with CV outcomes in T2DM patients with a history of coronary artery disease and on optimal medical therapy.


1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853.

2. Gore MO, McGuire DK. A test in context: hemoglobin A1c and cardiovascular disease. J Am Coll Cardiol. 2016;68:2479–2486.

3. Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, Gibson CM, Granger C, Menon V, Montalescot G, Rader D, Tall AR, McErlean E, Wolski K, Ruotolo G, Vangerow B, Weerakkody G, Goodman SG, Conde D, McGuire DK, Nicolau JC, Leiva-Pons JL, Pesant Y, Li W, Kandath D, Kouz S, Tahirkheli N, Mason D, Nissen SE; ACCELERATE Investigators. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med. 2017;37 6:1933-1942.

Find this article online at J Am Heart Assoc.

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