I can't think of any particular reason that wouldn't work, unless Voldemort or the Death Eaters in general have some way of stopping them prior to the attack. Maybe the anti-disapparition jinx (which is an area of effect spell rather than a targeted one according to the Potter wiki) also affects portkeys? Or perhaps there's another spell. The Death Eaters might simply jinx their targets' houses before attacking.

If there weren't some way of preventing people from using them, I'd think having a portkey in the house in a readily accessible place, to teleport out of harm's way, would be standard response for anyone at particular risk in the war. Given that this apparently didn't stop the Death Eaters, I assume that it's preventable.