New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.