It depends. If you want to make ConfigVars persistant, you probably need to set them in the Reaper.ini as well, or otherwise, it will not exist after restarting Reaper.
There are exceptions though, like the config-var that changes the font-size of the IDE, this will be altered in the reaper.ini by Reaper itself.
Oh, and config-vars that are of the project(usually those set in the Project-Settings-dialog) persist, when you save the project.
You need to experiment with it a little. Setting some of the config-vars is not really helpful. If in doubt, try to find an action that does this for you.
I made a list of which action sets which config-var in the first post of this thread. Just check, if one of them sets defsendflags as well.
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