Alirocumab Plus Statin Lowers Cardiac Event Risk for Patients with Diabetes, ACS

Kausik Ray, MD, ChB

New data from the ODYSSEY OUTCOMES trial has revealed that for patients with diabetes who have recently experienced acute coronary syndrome (ACS), a combination of statins and alirocumab (Praulent, Sanofi) may reduce the risk of future cardiac events by more than double that of patients with prediabetes or normoglycemia on the same regimen with similar cardiac histories.

The results showed that the absolute risk reduction (ARR), for patients with diabetes was the highest among the groups, with the regimen of statins plus the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor lowering risk by 2.3% (hazard ratio [HR], 0.84; 95% CI, 0.74 to 0.97). Comparatively, the ARR for patients with prediabetes was 1.2% (HR, 0.86; 95% CI, 0.74 to 1.00) and the ARR for patients with normal glucose levels was 1.2% (HR, 0.85; 95% CI, 0.70 to 1.03).

Presented at the American Diabetes Association’s 78^th Annual Scientific Sessions in Orlando, Florida, this new analysis of the data included subgroups of 5444 patients with diabetes (28.8% of the total patient population), 8246 (43.6%) with prediabetes, and 5234 (27.7%) with normal glucose levels.

The total trial featured almost 19,000 participants with recent ACS and low-density lipoprotein-cholesterol (LDL-C) levels of higher than 70 mg/dL on a maximum-tolerated dose of atorvastatin or rosuvastatin. They were randomly assigned to a 75 mg group or placebo. The therapy was blindly increased to 150 mg or decreased to placebo to achieve an LDL-C of 25-50 mg/dL.

"The analyses show adding alirocumab to maximally tolerated statins reduced the overall incidence of MACE, and the absolute risk reduction was highest among those with diabetes when compared to people with prediabetes or people without diabetes," said Kausik Ray, MD, ChB, a professor of public health at the School of Public Health of Imperial College in London, in a statement.

Ray noted that the success of the combination of medications is attributable to the fact that the baseline absolute risk for patients with diabetes was so high. “The other groups that took the alirocumab also derived benefit, but the benefit was slightly less because their risk was lower,” he said.

“Additionally, some genetic studies have suggested that lowering bad cholesterol with this type of therapy might push people with prediabetes to diabetes,” Ray said. “We found no evidence of new-onset diabetes for the people in the study who took alirocumab. These results suggest intensive cholesterol-lowering using the combination of statins and alirocumab offers us a means to significantly reduce heart disease risk in this patient population."

Previously, at the 67^th American College of Cardiology’s Scientific Sessions, also in Orlando, the therapy was shown to reduce major adverse cardiovascular events (MACE), as well as reduce all-cause mortality when compared to placebo in patients with ACS with elevated levels of atherogenic lipoproteins despite intensive or maximum-tolerated statin therapy.

That ARR was shown to be of 1.6% (HR, 0.85; 95% CI, 0.78—0.93; P = .0003) in MACE—a composite including coronary heart disease (CHD), non-fatal myocardial infarction (MI), ischemic stroke, or unstable angina requiring hospitalization—over the course of the 4-year study period.

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