SUB-ANALYSIS: DATA IN PATIENTS WITH OR WITHOUT DIABETES

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Ray KK, Colhoun HM, Szarek M, et al.; for the ODYSSEY OUTCOMES Committees and Investigators.
Lancet Diabetes Endocrinol. 2019 Aug;7(8):618–628. Epub 2019 Jul 1.

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Efficacy of alirocumab on CV events by baseline glycemic status1


 

Effects of treatment with alirocumab on measures of glycometabolic safety (HbA1c and fasting serum glucose) and new-onset diabetes1



 

Effect of alirocumab on a range of lipid parameters by baseline glycemic status (LDL-C, HDL-C, non-HDL-C, and triglycerides)1


 

50% increased risk of MACE in diabetes vs non-diabetes populations1

The 2x higher rate of MACE in patients with diabetes was associated with a greater ARR (2.3%) on alirocumab vs that of patients without diabetes (ARR 1.2%) on alirocumab1

There was no increased risk of new-onset diabetes in patients treated with alirocumab vs placebo*1

Footnotes

ARR=absolute risk reduction; CV=cardiovascular; LDL-C=low-density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; HbA1c=glycated hemoglobin; MACE=major adverse cardiovascular events.
*Median follow-up of 2.8 years. 44% were eligible to be followed for 3-5 years1,2

Glycemic status definitions and baseline characteristics

View glycemic status definitions

 View baseline characteristics
 

KEY FINDINGS

50% increased risk of MACE in diabetes vs non-diabetes subpopulations1

Despite optimal standard of care, there remains a very high risk of recurrent CV events in patients with diabetes.2

  • Normoglycemia

    Prediabetes

     Diabetes

  • Normoglycemia

    Prediabetes

     Diabetes

  • Normoglycemia

    Prediabetes

     Diabetes

  • Normoglycemia

    Prediabetes

     Diabetes

  • Normoglycemia

    Prediabetes

     Diabetes

In order to contextualize the effect of alirocumab on the primary endpoint (prespecified analysis) by diabetes status, we compared the association between presence of diabetes or absence of diabetes at study entry on the risk of the composite primary endpoint and its components (post hoc analysis) in the placebo group.1

There was approximately 2x incidence of CV events in patients with diabetes vs those without diabetes.

There was a significantly increased risk of MACE, CHD death, nonfatal MI, and ischemic stroke in patients with diabetes at baseline vs those without diabetes.

 

KEY FINDINGS

The 2x higher rate of MACE in patients with diabetes was associated with a greater ARR (2.3%) on alirocumab vs that of patients without diabetes (ARR 1.2%) on alirocumab1

Alirocumab treatment resulted in consistent MACE relative risk reduction regardless of glycemic status1

Relative and absolute risk reduction with alirocumab by baseline glycemic status1

In patients with diabetes, the absolute risk reduction was 2.3%, twice that observed in patients without diabetes in the other two glycemic status groups, with a significant statistical interaction (p=0.0019),1 suggesting that in a higher risk group with a very similar baseline LDL-C, lowering LDL-C to between 25 mg/dL and 50 mg/dL is associated with a larger absolute benefit.

 

KEY FINDINGS

Alirocumab did not adversely affect glycemic or glycometabolic parameters or increase the risk of new onset diabetes1

In patients without diabetes, alirocumab did not adversely affect new-onset diabetes vs placebo.1

Post-randomization new-onset diabetes by baseline glycemic status1 † ‡

 Alirocumab

Placebo

There was no increased risk of new-onset diabetes in patients treated with alirocumab vs placebo.*1

Alirocumab did not adversely affect HbA1c, fasting plasma glucose levels, or new-onset diabetes in patients with normoglycemia or prediabetes at baseline.1

Definition of new-onset diabetes

Patients with normoglycemia or prediabetes at baseline were required to meet one or more of the following:1

  • ≥1 HbA1c value of ≥6.5% (48 mmol/mol)
  • Two fasting serum glucose values of at least 126 mg/dL (7.0 mmol/L)
  • An investigator-reported diabetes-related adverse event
  • Initiation of diabetes medication for a diagnosis of diabetes that was confirmed by an external expert committee

Among patients without diabetes prespecified at baseline, 5955 (44.2%) were eligible for three to five years of follow-up.1

Footnotes

ARR=absolute risk reduction; CHD=coronary heart disease; CI=confidence interval; CV=cardiovascular; CVOT=cardiovascular outcomes trial; HbA1c=glycated hemoglobin; HDL-C=high-density lipoprotein cholesterol; HR=hazard ratio; LDL-C=low-density lipoprotein cholesterol; MACE=major adverse cardiovascular events; MI=myocardial infarction; PCSK9=proprotein convertase subtilisin/kexin type 9; RRR=relative risk reduction.

*Median follow-up of 2.8 years, 44% were eligible to be followed for 3–5 years.1,2
‡ Patients with prediabetes had a hazard ratio of 0.97 (95% CI 0.87–1.09), and patients with normoglycemia had a hazard ratio of 1.30 (95% CI 0.93–1.81); p interaction=0.11 in a post hoc analysis.
† Includes patients categorized as having prediabetes or normoglycemia.

Other findings

    Lipid concentrations at four months by baseline glycemic status1

    Analyzed in the intention-to-treat populations.

    The cholesterol-lowering effect of alirocumab was consistent across the three glycemic status groups, with >60% reduction in LDL-C from baseline to 16 weeks.1

    Footnotes

    CV=cardiovascular; HbA1c=glycated hemoglobin; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol.

    In patients without diabetes, alirocumab did not adversely affect HbA1c or fasting glucose vs placebo.1

    •  Alirocumab

      Placebo

    •  Alirocumab

      Placebo

    Alirocumab did not adversely affect fasting glucose levels during the course of the trial.

    Footnotes

    *Error bars are 95% CIs. Only post-randomization values before diabetes medication was started were included in the analysis.  CI=confidence interval; HbA1c=glycated hemoglobin.

    1. Ray K, et al. Lancet Diabetes Endocrinol 2019:7(8)618–628.
    2. Schwartz G, et al. N Engl J Med 2018;379(22):2097-2107.

Read more about this sub-analysis

Continue your ODYSSEY

The ODYSSEY OUTCOMES story

Study design

Sub-analysis

Alirocumab and diabetes

Sub-analysis

Sub-analysis of the polyvacular patients