Card advantage is determined based on what actually happens in game. For example, Annihilate will be card advantage if it resolves normally targeting a creature an opponent controls—you lose one card from your hand but you also draw a card, for a net gain of zero cards, and your opponent loses one card, so you’re up one card relative to them. However, if the target creature has indestructible, you and your opponent both have a net gain of zero cards, so that’s not card advantage.