Dennis W. Wahr

Phase I Drug and Light Dose-Escalation Trial of Motexafin Lutetium and Far Red Light Activation (Phototherapy) in Subjects With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention and Stent Deployment Procedural and Long-Term Results

Background—Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. Methods and Results—An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. Conclusions—This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium.

Photodynamic therapy (PDT) has been approved as a tissue‐specific light‐activated cytotoxic therapy for many diseases. The ability of PDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque. Biotechnology has developed a new generation of selective photosensitizers and catheter‐based technological advances in light delivery have allowed the introduction of PDT into the vasculature. The largest experience to date is with motexafin lutetium (MLu, Antrin), an expanded porphyrin (texaphyrin) that accumulates in plaque. The combination of the motexafin lutetium and endovascular illumination, or Antrin phototherapy, has been shown to reduce plaque in animal models. Antrin phototherapy generates cytotoxic singlet oxygen that has been shown to induce apoptosis in macrophages and smooth muscle cells. The safety, tolerability, and preliminary efficacy of Antrin phototherapy has been assessed in a phase 1 dose‐ranging clinical trial in subjects with peripheral artery disease and is currently being examined in a phase 1 study in subjects with lesions of the native coronary arteries undergoing stent implantation. The preliminary results suggest that Antrin phototherapy is safe, well tolerated, and nontraumatic. Cathet Cardiovasc Intervent 2002;57:387–394.

Venture wire control catheter

We wished to test the safety and efficacy of a novel wire control catheter for use during percutaneous coronary intervention. The ability to vary the angulation of the tip of an intravascular guidewire would often be desirable. Previous attempts to produce deflectable‐tip guidewire systems have met with limited success. The Venture wire control catheter (Velocimed, Minneapolis, MN) was used to facilitate percutaneous coronary intervention in 20 patients. There were no device‐related complications. Percutaneous coronary intervention was successful in all patients. Our initial experience with the Venture wire control catheter has been favorable.

Does the beneficial effect of distal protection in saphenous vein graft interventions vary with lesion length? A SAFER (Saphenous Vein Graft Angioplasty Free of Emboli Randomized) substudy

Background: The SAFER trial demonstrated a dramatic reduction in Major Adverse Clinical Events (MACE: a composite of death, Ml or revascularfzation) acutely and at 30 days following saphenous vein graft (SVG) percutaneous intervention (PCI) with the use of the Percusurge GuardWire TM distal protection device. This benefit was anributed to the prevention of distal migration of atherosclerotic debris with the device. Methods: We sought to evaluate if the reduction in MACE seen in the SAFER trial varied with the length of the treated lesion. We divided lesion lengths into quartiles and performed a stratified analysis to evaluate for effect modification by lesion length on the reduction in MACE with the GuardWireTM compared to patients treated with no distal protection. Rasutts: Of the 751 lesions treated, longer lesions were associated with a higher incidence of MACE in both the control group (p=O.Oll) and GuardWireTM group (p=O.OOl). As demonstrated in the table, use of the GuardWireTM was associated with a reduction in MACE in each quartile of lesion length. With multivariable modeling, shorter lesions showed a trend toward a greater relative reduction in MACE with use of the GuardWireTM (p=O.O97).