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Zerlasiran for the Treatment of Atherosclerotic Cardiovascular Disease—Reply
In Reply Ms Wu and colleagues raise the concern that use of PCSK9 inhibitors may have resulted in underestimation of the lipid-lowering effect of zerlasiran in our trial. We think this is highly unlikely. Although PCSK9 inhibitors slightly reduce lipoprotein(a), the trial protocol (posted with the article), required trial participants receiving lipid-modifying therapy at trial entry (including statins, PCSK9 inhibitors, and ezetimibe) to be taking a stable, maximum-tolerated regimen for a minimum of 8 weeks with no changes to existing regimens, and introduction of new lipid-modifying regimens was not permitted after screening. For monoclonal antibody PCSK9 inhibitors, a stable dose was defined as at least 4 doses at a consistent dose level. Given the requirement for stable background lipid-lowering therapies, the effects of zerlasiran on lipoprotein(a) reduction was not likely influenced by use of PCSK9 inhibitors.
In Reply Ms Wu and colleagues raise the concern that use of PCSK9 inhibitors may have resulted in underestimation of the lipid-lowering effect of zerlasiran in our trial. We think this is highly unlikely. Although PCSK9 inhibitors slightly reduce lipoprotein(a), the trial protocol (posted with the article), required trial participants receiving lipid-modifying therapy at trial entry (including statins, PCSK9 inhibitors, and ezetimibe) to be taking a stable, maximum-tolerated regimen for a minimum of 8 weeks with no changes to existing regimens, and introduction of new lipid-modifying regimens was not permitted after screening. For monoclonal antibody PCSK9 inhibitors, a stable dose was defined as at least 4 doses at a consistent dose level. Given the requirement for stable background lipid-lowering therapies, the effects of zerlasiran on lipoprotein(a) reduction was not likely influenced by use of PCSK9 inhibitors.
