The following chart shows how fighting guards in League S is going for me. Two and only two of the guards do not have a 4-star Twinkie. Can you guess which ones?
If you said 56 and 57 then you guessed correctly. Yeah, those are the ones I’m picking on most. 
You can also tell that guards 58 and 60 are not my friends, not that I intend to teach them a lesson anytime soon. They’re teaching me and I choose to skip class!
You’d think guard 55 would be the easiest. Well, that’s what you get for thinking. I need a pet that will protect me against confusion, because things really go south if that kicks in.
If you are racing to make it to League S, be careful what you wish for. Keep in mind that I do have a 4-star Twinkie, and 9 other pets. My heroes were relatively well prepared.
It would have been smarter and cheaper for me though, over the long-term, if I had stayed in League A (where I never lost a battle to any of the guards). No regrets. I felt compelled to satisfy my curiosity. At the very least, let my adventures serve as a warning to others. 
“The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of infinity, and it was not meant that we should voyage far.” - H.P. Lovecraft
He spoke of League S, no doubt.
I will try to come up with some useful advice before you get here. The best so far is to avoid getting here until you are ready. If you are even remotely struggling fighting the guards in League A, then you are definitely not ready for League S. These guards are much, much tougher. 