Now, over 30 years later, we conduct ASPREE, ARRIVE, and ASCEND. The participants in these trials either had good blood pressure control on their own or they were treated. They either had good cholesterol on their own, or they were treated. They either had good glucose control, or they were treated. With much less damage to the blood vessel wall, plaque ruptures occur less often, and aspirin has less work to do—less damage, fewer plaque ruptures, and fewer clots to break up.
My take on this aspirin story is not that aspirin is not working but that we have managed the other risk factors so well that clot formation is no longer rampant. I don’t think that we were wrong for all these years recommending aspirin for primary prevention. Aspirin did provide a benefit, but now we are also taking care of the root causes of vascular damage. If a trial was conducted currently among patients who refused blood pressure medications, refused statins, refused diabetes medications, and were still smoking, then I think aspirin would shine again.