ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.
Dr. Kausik Ray
“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”
Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.
The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.
During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.
In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.
The ARRs for the prediabetes and normoglycemia groups were both 1.2%.
Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”
According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.
Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.
“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”
Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”
In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”
Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”
ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.
SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.