DPS champions could maximize the effect of this item by stacking it with attack speed items and other on hit items such as Malady, Ionic Spark and Wit's End.
The unique passive of Madred's Bloodrazor dealt magic damage. Therefore, the unique effect could have its damage reduced by magic resistance items such as Negatron Cloak.
Malady synergized with Madred's Bloodrazor since it reduced the magic resistance of your target with each hit.
Champions who can proc on hit effects multiple times in quick succession did best with this item, such as Warwick'sInfinite Duress and Renekton'sRuthless Predator, which could result in the quick destruction of health stacking champions or tanks that lack magic resistance.
The item was removed because it gave too many odd stats, and its on-hit damage was magic damage which made it hard to put in an effective item build that would still synergize with the auto attacking champions that would build it (Warwick being one of the few excepetions). It was replaced with Blade of the Ruined King.