The best way to ensure that your recipients no longer receive emails, is to de-register them from the address book. Create an excel file with all addresses that should be unsubscribed/deregistered.
Import this file as normal and check the box ‘Import as blacklist’ when you import them. This means that all of the addresses in this file are placed onto the blacklist, and are therefore deregistered. Addresses on the blacklist are never written to again, even if you select them, along with other recipients, when sending a newsletter.
This method is essentially safer than simply deleting the recipient, because deleted addresses can simply be imported again as new. Deregistered addresses cannot be imported again.
If de-registered addresses are deleted and then imported as new, they remain deregistered.