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Alirocumab plus statin cuts cardiac events in patients with diabetes, ACS
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ORLANDO, Fla. — In a new analysis of the ODYSSEY Outcomes trial, patients with recent acute coronary syndrome and diabetes derived the greatest benefit, in terms of major adverse cardiac events, after treatment with the PCSK9 inhibitor alirocumab combined with maximum-tolerated statin therapy compared with patients with acute coronary syndrome and prediabetes or normal glucose levels.
As previously reported by Cardiology Today , the overall ODYSSEY Outcomes results, presented at the American College of Cardiology Scientific Session in March, showed that reducing LDL to very low levels with subcutaneous injections of alirocumab (Praluent, Sanofi/Regeneron) every 2 weeks lowered risk for major adverse cardiac events and all-cause mortality in patients with acute coronary syndrome (ACS) on maximum-tolerated statin doses.
The new prespecified analysis looked at absolute risk reduction with alirocumab plus statin therapy based on glycometabolic status. Of the 18,924 patients with baseline LDL levels greater than 70 mg/dL who had ACS within 1 to 12 months before enrollment in ODYSSEY Outcomes, 27.7% had normal glucose levels, 28.8% had diabetes and 43.6% had prediabetes.
The absolute risk reduction for major adverse cardiac events was nearly doubled in patients with diabetes and recent ACS: 2.3% (HR = 0.84; 95% CI, 0.74-0.97) vs. 1.2% in those with prediabetes (HR = 0.86; 95% CI, 0.74-1) and 1.2% in those with normal glucose levels (HR = 0.85; 95% CI, 0.7-1.03).
Median follow-up was 34 months.
“By baseline glycometabolic status, going from normoglycemia to prediabetes to diabetes, event rates for major adverse cardiac events are almost double by the time you get to diabetes. The overall treatment effect for 4-point [major adverse cardiac events] over about 30 months is a 15% relative risk reduction. There is no interaction between the three groups, meaning that the benefit is absolutely constant,” Kausik K. Ray, MD, professor of public health in the department of public health and primary care at Imperial College London, said during a press conference. “If you move to look now at absolute benefit, what you see is a much bigger absolute benefit in the people with diabetes — twice as large as the other two groups.”
In other results, combined treatment yielded similar reductions in LDL across all three groups and no difference in HbA1c change or fasting glucose during follow-up, according to Ray. The researchers also looked at new-onset diabetes, adjudicated by a masked committee, and found no increased risk.
Patients enrolled in ODYSSEY Outcomes had their alirocumab doses titrated between 75 mg and 150 mg every 2 weeks to achieve an LDL level of 25 mg/dL to 50 mg/dL. The primary endpoint was time to first major adverse cardiac events, defined as coronary heart disease death, nonfatal myocardial infarction, ischemic stroke or unstable angina requiring hospitalization.
“In a population with diabetes and ACS with LDL above 70 mg/dL, currently the American Association of Clinical Endocrinologists guidelines recommend an LDL goal of about 55 mg/dL for this patient population at extreme risk. The present data would suggest that moving that goal to 25 to 50 mg/dL would give you a bigger absolute benefit in a high-risk population ... even though the relative risk remains constant.
“We can actually provide really robust reassurance — by looking at HbA1c consistently during the course of the trial, glucose levels and through the adjudicated committee that we put together looking at new-onset diabetes — that there is no adverse effect on glycometabolic control over ... a 3-year period,” Ray said. – by Katie Kalvaitis
Reference:
Ray KK, et al. 6-LB. Presented at: American Diabetes Association 78th Scientific Sessions; June 22-26, 2018; Orlando, Fla.
Disclosures: Ray reports he is a consultant for Amgen, Merck, Sanofi and The Medicines Company and receives research support from Amgen, AstraZeneca, Boehringer Ingelheim, Esperion Therapeutics, Kowa Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Regeneron and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.