The four horns of the gold altar (see Revelation 8:3) appear with the sixth trumpet blast. Many excavations have found altars with pointed horns at their four corners (see study note on Exodus 27:2).
The voice has God's authority to command the release of the four angels.
These angels are bound, indicating their evil nature (compare Revelation 20:2; 1 Enoch 10; contrast Revelation 7:1). Their location at the great Euphrates River likely refers to Assyria and Babylon, empires that destroyed the kingdoms of Israel and Judah, symbolizing destruction (see 2 Kings 17:22–24; 25:1–11).