Approximately 18 million Americans have peripheral artery disease (PAD), and 2 million of these patients suffer from critical limb ischemia (CLI)1,2, the end stage of PAD3. CLI is highly prevalent in older patients with diabetes and/or end-stage renal disease4, and is associated with high risk of amputation and mortality5. Even though the rates of amputations in the general PAD population are declining, primary amputation continues to be first-line therapy in up to 67% of CLI patients.5–9 In addition, of these patients receiving primary amputation, 73%7 had no diagnostic angiogram and 54%10 received no vascular procedure prior to the amputation. The results following the primary amputation can be devastating — 27% of the patients will have one or more re-amputation(s) within 1 year11, 35% will have a higher level of limb loss12, and 55% will get the other limb amputated within 2-3 years13. In addition, the mortality rates after primary amputation are very high, with 1-year mortality rates ranging from 9 to 33%11,12,14,15, and 5-year mortality rates ranging from 26 to 82%11,14–16.
The LIBERTY 360˚ study results (30-day) that were recently presented at the AMPutation Prevention Symposium (AMP 2016) revealed promising hope for Rutherford Class 6 (R6) CLI patients. Briefly, the LIBERTY 360˚ study17 is a prospective, observational, multi-center study with liberal inclusion criteria and few exclusions, meant to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD, including CLI. The study included any FDA-approved technology to treat claudication and CLI. Four core laboratories were utilized for independent analysis of the following: procedural and lesion success (SynvaCor, Springfield, Ill.), rates of target lesion revascularization (TLR)/target vessel revascularization (TVR) events (SynvaCor, Springfield, Ill.), duplex ultrasound interpretations (VasCore, Boston, Mass.), wound status, quality of life, 6-minute walk test (CPC Clinical Research, Aurora, Colo.), and economic analysis (Mid America Heart Institute, Kansas City, Mo.). The LIBERTY 360° study enrolled 1204 patients across 51 sites in the United States:
- 500 patients in the Claudicant Rutherford Class 2-3 (R2-3) arm;
- 589 patients in the CLI Rutherford Class 4-5 (R4-5) arm;
- 100 patients in the CLI Rutherford Class 6 (R6) arm.
As presented at AMP 2016, procedural complications rarely (0.8 to 2%) resulted in post-procedural hospitalization in all Rutherford classes and 78% of R6 subjects were discharged to their homes. Quality of life also improved from baseline across all Rutherford classes. At 30 days, the rate of freedom from major adverse events (MAE) was 99% in R2-3, 95.7% in R4-5 and 90.7% in R6 (Table 1). Only 4.2% of the LIBERTY 360˚ R6 subjects had a major amputation at 30 days — much lower than the 22-67%5–9 primary major amputation rates seen in the literature for CLI patients that do not receive endovascular intervention (Figure 1).
Early findings in this novel, all-comers PAD study suggest that “watchful waiting” in Rutherford Class 2-3 and “primary amputation” in Rutherford Class 6 may not be necessary. Percutaneous vascular interventions can be successful in these patient populations as well.
Acknowledgements. The authors thank all investigators of the LIBERTY 360˚ Study for their contributions to the study enrollment.
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- Schiavetta A, Maione C, Botti C, Marino G, Lillo S, Garrone A, et al. A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study. Stem Cells Transl Med. 2012 Jul; 1(7): 572-578.
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- Adams GL, Mustapha J, Gray W, Hargus NJ, Martinsen BJ, Ansel G, Jaff MR. The LIBERTY study: Design of a prospective, observational, multicenter trial to evaluate the acute and long-term clinical and economic outcomes of real-world endovascular device interventions in treating peripheral artery disease. Am Heart J. 2016 Apr; 174: 14-21.
1Metro Health Hospital, Wyoming, Michigan;
2Cardiovascular Systems, Inc., St. Paul, Minnesota.
Disclosures: Jihad A. Mustapha, MD, reports consulting agreements with Cardiovascular Systems, Inc. Zsuzsanna Igyarto, PhD, and Brad J. Martinsen, PhD, report that they own stock in and are employed by Cardiovascular Systems, Inc.
The authors can be contacted via Jihad A. Mustapha, MD, at email@example.com, or by phone at (616) 252-5020.