AppleTalk for VMS 2.1 was not tested with VMS 5.4, because VMS 5.4 was not released at the time version 2.1 was tested. However, AppleTalk for VMS 2.1 should work under VMS 5.4.
There is a larger issue here that ties into your question about AppleTalk for VMS 3.0. In fact, there is only one choice, and that is AppleTalk for VMS 3.0 (as part of PATHWORKS, formerly DEC LanWORKS). Version 2.1 was an interim release intended solely to provide AppleTalk Phase 2 compatibility until version 3.0 was released. AppleTalk for VMS 3.0 works under VMS 5.4, and that is the current VMS product superseding all other releases.
If you're running older, AppleTalk Phase 1, versions of AppleTalk for VMS, you should start moving toward AppleTalk Phase 2 and AppleTalk for VMS 3.0. The only potential difficulty here is if you have products that require the AppleTalk for VMS 2.x API. In this case, you can go to AppleTalk for VMS 2.1 until those products have been revised to support the new API of AppleTalk for VMS 3.0.