Ludogorets's hopes of reaching the UEFA Champions League group stage for a second successive season were dashed in the second qualifying round by Milsami.
The Bulgarian champion held Liverpool 2-2 in Group B last season and enjoyed a victory over Basel, before finishing bottom of a group that also included Real Madrid.
But it will not be mixing with such illustrious opponents this season after goals from Gheorghe Andronic and Petru Racu gave 10-man Milsami a 2-1 win on the night, and a 3-1 aggregate success.
Serbian champion Partizan is into the third round of qualifying after a 2-0 victory in Gori over Dila, the triumph in Georgia enough to see it progress 3-0.
Zaven Badoyan gave Pyunik a 1-0 victory over Molde in Armenia, but the striker's goal was not enough to see his side through as the visitor cruised into the next round 5-1 on aggregate.
There was drama in Tel Aviv as Maccabi turned a first-leg deficit around against Hibernians, the Israeli title winner running out a 5-1 victor on the night – 6-3 on aggregate – to take its place in round three, where it will meet Viktoria Plzen.
After winning its first leg with Ventspils 3-1 last week, HJK only needed Mike Havenaar's second-half strike to seal its progress in Helsinki.
A Tomas De Vincenti effort on the hour proved decisive for APOEL as it snuck through on the away goals rule against Vardar.
The Cypriot outfit will now face Midtjylland, which recorded a 2-0 triumph – 3-0 on aggregate – over Lincoln Red Imps.
It is joined in the third round by Malmo after its 1-0 win over 10-man Zalgiris, while Crusaders's 3-2 victory over Skenderbeu Korce was not enough to prevent it losing 6-4 on aggregate.