edifoligide and Peripheral-Vascular-Diseases

Vein bypass surgery is an effective therapy for atherosclerotic occlusive disease in the coronary and peripheral circulations; however, long-term results are limited by progressive attrition of graft patency. Failure of vein bypass grafts in patients with critical limb ischemia results in morbidity, limb loss, and additional resource use. Although technical factors are known to be critical to the success of surgical revascularization, patient-specific risk factors are not well defined. In particular, the relationship of race/ethnicity and gender to the outcomes of peripheral bypass surgery has been controversial.. We analyzed the Project of Ex Vivo Vein Graft Engineering via Transfection III (PREVENT III) randomized trial database, which included 1404 lower extremity vein graft operations performed exclusively for critical limb ischemia at 83 North American centers. Trial design included intensive ultrasound surveillance of the bypass graft and clinical follow-up to 1 year. Multivariable modeling (Cox proportional hazards and propensity score) was used to examine the relationships of demographic variables to clinical end points, including perioperative (30-day) events and 1-year outcomes (vein graft patency, limb salvage, and patient survival). Final propensity score models adjusted for 16 covariates (including type of institution, technical factors, selected comorbidities, and adjunctive medications) to examine the associations between race, gender, and outcomes. Among the 249 black patients enrolled in PREVENT III, 118 were women and 131 were men. Black men were at increased risk for early graft failure (hazard ratio [HR], 2.832 for 30-day failure; 95% confidence interval [CI], 1.393 to 5.759; P=0.0004), even when the analysis was restricted to exclude high-risk venous conduits. Black patients experienced reduced secondary patency (HR, 1.49; 95% CI, 1.08 to 2.06; P=0.016) and limb salvage (HR, 2.02; 95% CI, 1.27 to 3.20; P=0.003) at 1 year. Propensity score models demonstrate that black women were the most disadvantaged, with an increased risk for loss of graft patency (HR, 2.02 for secondary patency; 95% CI, 1.27 to 3.20; P=0.003) and major amputation (HR, 2.38; 95% CI, 1.18 to 4.83; P=0.016) at 1 year. Perioperative mortality and 1-year mortality were similar across race/gender groups.. Black race and female gender are risk factors for adverse outcomes after vein bypass surgery for limb salvage. Graft failure and limb loss are more common events in black patients, with black women being a particularly high-risk group. These data suggest the possibility of an altered biological response to vein grafting in this population; however, further studies are needed to determine the mechanisms underlying these observed disparities in outcome.

Topics: Aged; Asian People; Black People; Comorbidity; Female; Follow-Up Studies; Hispanic or Latino; Humans; Incidence; Ischemia; Limb Salvage; Male; Oligonucleotides; Peripheral Vascular Diseases; Risk Factors; Sex Distribution; Survival Analysis; Treatment Failure; Vascular Patency; Vascular Surgical Procedures; Veins; White People

Patients who require infrainguinal revascularization for critical limb ischemia (CLI) are at elevated risk for cardiovascular events. The PREVENT III study was a prospective, randomized, multicenter, phase 3 trial of edifoligide for the prevention of vein graft failure in patients with CLI. We examined the baseline characteristics, perioperative medical therapies, and 30-day incidence of major cardiovascular events in the PREVENT III cohort.. Demographics, medical and surgical history, mode of presentation for the index limb, procedural details, and concomitant medications were reviewed for all patients enrolled in PREVENT III (N = 1,404). Major adverse cardiovascular events, including death, myocardial infarction, or cerebrovascular event (stroke or transient ischemic attack) were tabulated. Univariate and multivariate analyses were performed to discern factors that were associated with the utilization of medical therapies and with perioperative events.. Demographics and comorbidities reflected a population with diffuse, advanced atherosclerosis. Perioperative mortality was 2.7%, and major morbidity included myocardial infarction in 4.7% and stroke/transient ischemic attack in 1.4%. Among this population of CLI patients, 33% were not on antiplatelet therapy at study entry, and 24% were not receiving antithrombotics of any type. In addition, 54% of patients were not receiving lipid-lowering therapy, and 52% were not prescribed beta-blocker medications at study entry. On multivariate analysis, race was a significant determinant of antithrombotic utilization, with African-American patients less frequently treated both at baseline and discharge (adjusted odd ratios, 0.5 and 0.6, P < .0001). Antithrombotic and beta-blocker drug usage increased in the overall cohort from baseline (76% and 48%) to discharge (88% and 60%; P < .0001). Patients treated in a university hospital setting were more likely to be prescribed antiplatelet, lipid-lowering, and beta-blocker medications. Advanced age (>75 years), coronary artery disease (prior myocardial infarction or revascularization), and dialysis-dependent renal failure were associated with an increased 30-day risk of death, myocardial infarction, or stroke. Protective effects of beta-blocker and lipid-lowering medications were noted in these defined subgroups.. A significant percentage of the population that undergoes surgical revascularization for CLI is not prescribed therapies of proven benefit in reducing cardiovascular events. Utilization of antithrombotics and beta-blockers increases during hospitalization for limb salvage surgery but that of lipid-lowering therapy does not. African-American patients appear to be at greater risk for undertreatment with antithrombotics, and the data suggest that patients undergoing leg bypass surgery in a university hospital setting receive more comprehensive medical treatment of atherosclerosis. Treatment guidelines for medical therapy are needed to standardize care and improve outcomes for patients with CLI.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Vessel Prosthesis; Cardiotonic Agents; Chi-Square Distribution; Clinical Trials, Phase III as Topic; DNA; Double-Blind Method; Female; Graft Occlusion, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inguinal Canal; Ischemia; Leg; Limb Salvage; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Oligonucleotides; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors