When would you consider initiating patients with CAD and aortic stenosis on PCSK9 inhibitors (as an adjunct to statin therapy), given favorable findings in the FOURIER trial?

There are limited data to support PCSK9 inhibitors in the treatment of aortic stenosis, and in fact, most is theoretical. Elevation of lipoprotein (a) levels independently increases the risk of in early-onset CAD and calcific aortic stenosis. Lp(a) levels are lowered by PCSK9 inhibitors by ~20-30%, and in an exploratory analysis in the FOURIER trial - designed to test the efficacy of evolocumab vs placebo in patients with CAD - they found that Lp(a) was associated with AS progression/AVR (no surprise) and that PCSK9 inh were associated with decreased AS events. 

It's important to know that this is an exploratory analysis and there were very few AS events. Key questions remain about whether lowering Lp(a) levels decreases risk of AS, and if so, is there an age interaction (i.e., when should therapy be started to see an effect on outcomes), and what level of Lp(a) elevation is meaningful to target? Hopefully, we'll have more randomized trial data to support these open and important questions.

Only if they have a guideline indication for non-statin therapy due to LDL being above goal. 

We shall see if lowering Lp(a) helps slow the progression of aortic stenosis with the new Lp(a) antisense med Pelacarsen. [Lp(a)FRONTIERS CAVS] trial is currently recruiting.