Various apparatuses and methods are described to treat vulnerable plaque with the use of combination drug therapy. In one embodiment, the apparatus has an elongated catheter body adapted for insertion in a body lumen, with a drug delivery device attached near a distal portion of the elongated body. The drug delivery device is configured to deliver a therapeutic or biologically active agent to stabilize a vulnerable plaque. In another embodiment, a drug eluting stent is delivered and deployed in conjunction with a second apparatus that delivers drug in pressurized retrograde perfusion. Still another embodiment uses a uniquely shaped balloon to deploy a stent while utilizing a drug infusion needle to inject drug into the vessel wall through a hollow guide wire.