WOUTER JUKEMA: In my opinion, guidelines should always be a bit conservative, because in general, guidelines say to you what is the minimum you should do for a patient. If you do less than the guideline says, you could be in trouble. You have to justify that. There can be justification for that. But this is what you, at least in general, should do.

So in my opinion, guidelines should not be too strict. That doesn't say that for certain high-risk patients where you-- and I think also guideline committees are completely aware that they are abundantly there-- you shouldn't be more aggressive. We do know that a lot of patients with aggressive progressive coronary atherosclerosis do not have very high LDL levels by nature.

We do know that if we lower these average cholesterol levels, they do far better. But we also do know that if we lower it even more, especially this high-risk individuals, it's even better. So where we, in the old days, considered an LDL cholesterol of 300 milligrams per deciliter acceptable, now we've gone to 200, to 100. But it's apparent that we can go lower.

And if you look at the sub-analysis from ODYSSEY Outcomes, 50 is probably, for a lot of patients that have aggressive atherosclerosis, is not an unreasonable goal. If they keep coming back, probably you are not doing enough. And these patients benefit even if your LDL cholesterol is already pretty low.

But if you lower it, they do even better. So 50, for some patients, can be a very reasonable goal. Can you go even lower? That could be. We did not see any harm from going lower. Of course, these trials are two, three, four years. So we do not know what the long run is for an LDL cholesterol below 50. Thus far, it seems safe, which is, I think, perfect reassurance to us, because we don't have immediately to worry. So that's good.

We allowed, in ODYSSEY Outcomes, to go as low as 15. And even there, we did not see any problems. Of course, we should realize that it's only a couple of years. We should have more information for more years. But it's reassuring that we didn't see any problem yet.

So a guideline should prescribe what we should be doing. But we do realize that we have patients that are, despite all the treatments that we give, and that are more or less within the guidelines, we should probably be more aggressive. And I think Fourier and ODYSSEY Outcomes especially give us the tools that we can be more aggressive. And for these patients-- and they will benefit from it.