Statins are independently associated with reduced mortality in patients undergoing infrainguinal bypass graft surgery for critical limb ischemia.
OBJECTIVE
Evidence suggesting a beneficial effect of cardioprotective medications in patients with lower extremity atherosclerosis derives largely from secondary prevention studies of heterogeneous populations. Patients with critical limb ischemia (CLI) have a large atherosclerotic burden with related high mortality. The effect of such therapies in this population is largely inferred and unproven.


METHODS
The Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III) cohort comprised 1404 patients with CLI who underwent lower extremity bypass grafting in a multicenter, randomized prospective trial testing the efficacy of edifoligide for the prevention of graft failure. Propensity scores were used to evaluate the influence of statins, beta-blockers, and antiplatelet agents on outcomes while adjusting for demographics, comorbidities, medications, and surgical variables that may influence drug use. Primary outcomes were major adverse cardiovascular events < or =30 days, vein graft patency, and 1-year survival assessed by Kaplan-Meier method. Potential determinants of 1-year survival were modeled using a multivariate Cox regression.


RESULTS
In this cohort, 636 patients (45%) were taking statins, 835 (59%) were taking beta-blockers, and 1121 (80%) were taking antiplatelet drugs. Perioperative major adverse cardiovascular events (7.8%) and early mortality (2.7%) were not measurably affected by the use of any drug class. Statin use was associated with a significant survival advantage at 1 year of 86% vs 81% (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98; P = .03) by analysis of both unweighted and propensity score-weighted data. Use of beta-blockers and antiplatelet drugs had no appreciable impact on survival. None of the drug classes were associated with graft patency measures at 1 year. Significant predictors of 1-year mortality by Cox regression modeling were statin use (HR, 0.67; 95% CI, 0.51-0.90; P = .001), age >75 (HR, 2.1; 95% CI, 1.60-2.82; P = .001), coronary artery disease (HR, 1.5; 95% CI, 1.15-2.01; P = .001), chronic kidney disease stages 4 (HR, 2.0; 95% CI, 1.17-3.55; P = .001) and 5 (HR, 3.4; 95% CI, 2.39-4.73; P < .001), and tissue loss (HR, 1.9; 95% CI, 1.23-2.80; P = .003).


CONCLUSIONS
Statin use is associated with improved survival in CLI patients 1 year after surgical revascularization. Further studies are indicated to determine optimal dosing in this population and to definitively address the question of relationship to graft patency. These data add to the growing literature supporting statin use in patients with advanced peripheral arterial disease.
Schanzer
Andres
A
Division of Vascular and Endovascular Surgery, University of Massachusetts, Worcester, MA, USA.
Hevelone
Nathanael
N
Owens
Christopher D
CD
Beckman
Joshua A
JA
Belkin
Michael
M
Conte
Michael S
MS
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D001161:Arteriosclerosis / Q000601:surgery*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007511:Ischemia / Q000401:mortality* / Q000601:surgery*; D007866:Leg / Q000098:blood supply*; D008297:Male; D009841:Oligonucleotides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D014182:Transplantation, Autologous; D014654:Vascular Patency / Q000187:drug effects; D014680:Veins / Q000637:transplantation
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009841:Oligonucleotides; D010975:Platelet Aggregation Inhibitors; C502518:edifoligide