There were a lot of observational data showing that Lp(a) is an independent marker of risk. That remains true. The key question is whether it is a modifiable mediator of risk, or merely a marker. Even if the latter, it does have value. I have been measuring levels for years, especially in patients with premature atherosclerosis or ischemic events. And even without a specific drug to lower it, I do shoot for tighter risk factor control, especially LDL cholesterol, when the Lp(a) levels are elevated.
I wasn’t sure if the trial would be positive or not. It was definitely a trial worth conducting. On the one hand, the epidemiology and genetics are reasonably strong. On the other hand, we have been burned by HDL cholesterol, which is also an independent marker of risk, but to date, not one that is modifiable by targeted pharmacotherapy. The only way to know for sure is to conduct large CV outcome trials, as was done here.
Whether the results might be due to the drug itself or whether the entire class does not make a difference in terms of CV outcomes is the million-dollar question. There are ongoing trials that will answer that question. It could be the specific drug. It could be that Lp(a) levels were not high enough at baseline. It could be that the population studied was not quite high risk enough clinically. It could be some combination of all those factors. It could also be that the levels of LDL were low enough that an incremental benefit could not be found. Analyses of HORIZON and ongoing trials will answer all the above questions.
