Leiter LA, et al. – A pooled analysis of 10 phase III ODYSSEY clinical trials was designed to evaluate the lipid–lowering efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in people with hypercholesterolaemia and prediabetes at baseline vs people with normoglycaemia at baseline in a pooled analysis of 10 ODYSSEY phase III trials. It was concluded that alirocumab treatment resulted in significant LDL cholesterol reductions from baseline that were similar in participants with prediabetes and those with normoglycaemia at baseline, with no effect on glycaemia and a safety profile similar to that of the control.

Methods

• For this research, people divided as having prediabetes had baseline HbA1c ≥39 mmol/mol (5.7%) and <48 mmol/mol (6.5%), or two baseline fasting plasma glucose values ≥5.6 mmol/l (100 mg/dl) but no more than one fasting plasma glucose value ≥7.0 mmol/l (126 mg/dl), or had specific terms reported in their medical history; people diagnosed with diabetes at baseline were excluded; and the remainder were classified as having normoglycaemia.
• For 24–104 weeks, participants received alirocumab or control (placebo/ezetimibe), with maximally tolerated statin in most cases.
• The preliminary adequacy endpoint was LDL cholesterol reductions from baseline to week 24 in the intention-to-treat population using the mixed-effect model with a repeated measures approach.

Results

• It was showed that reductions in LDL cholesterol from baseline to week 24 with alirocumab were 44.0–61.8% (prediabetes group) and 45.8–59.5% (normoglycaemia group).
• The evidence displayed that LDL cholesterol reductions were generally similar in those with and without baseline triglycerides ≥1.7 mmol/l (150 mg/dl) in both subgroups.
• The data indicated that alirocumab was not correlated with changes in HbA1c or fasting plasma glucose over time in either subgroup (up to 24 months’ follow-up).
• They noticed that adverse event rates were generally similar in those with and without prediabetes.