"Given the history of trials that use 3 point MACE as the primary endpoint, answer 2 seems most likely to me."

I have no idea what that means. Some CVOT trials w/ 3-point MACE outcome have expanded the number of patients in the trial at interim, some do not. What data (i.e. "Given the history") are you using to make this claim Noretreat? Name a few trials that have expanded the number of patients and we can probably find even more that did not.

"Adding 50% to the sample size would likely be largely USA patients and would mean the SSA is actually at 50% completion instead of 75%."

Is this a riddle? The sample size re-estimation analysis (SSRA) will occur once 188 3-point MACE events (75% of the 250 total) have been adjudicated. The SSRA won't be triggered if only 50% of events have occurred. What is likely to happen is if the SSRA recommends adding patients they will increase the number of MACE events required to end the trial (currently 250). Perhaps that is what you mean Noretreat. If at the SSRA (188 events) they decide to increase number of events to end the trial from 250 to 375 (just an example), then they would effectively no longer be at 75% (188/250) but instead around ~50% (188/375).

BearDownAZ