Author + information
- aDivision of Cardiovascular Medicine, The Vascular Center, University of California, Davis Medical Center, Sacramento, California
- bUniversity of Colorado, Division of Cardiology and VA Eastern Colorado Healthcare System, Denver, Colorado
- ↵∗Reprint requests and correspondence:
Dr. John R. Laird, UC Davis Medical Center, 4860 Y Street, Suite 3400, Sacramento, California 95817.
Critical limb ischemia (CLI), defined as ischemic rest pain or the presence of a nonhealing arterial ulcer or gangrene, is the most advanced and debilitating form of peripheral artery disease (PAD). An estimated 10% of patients with PAD progress to CLI within 5 years, with the annual incidence of CLI ranging between 500 and 1,000 new cases per 1 million individuals (1). Within 3 months from the time of diagnosis, 9% of CLI patients will die and 12% will require major amputation. One- and 2-year mortality rates of 21% and 31.6% have been reported (1). Collectively, CLI substantially affects patient quality of life and exerts a substantial economic burden to the overall health care system (1,2).
While optimal medical therapy is crucial for minimizing cardiovascular events in patients with CLI, revascularization remains the cornerstone of therapy for limb preservation and prevention of major amputation. For decades, surgical bypass has been the primary mode of revascularization in patients with CLI. However, many patients with CLI have inadequate target vessels for bypass or lack adequate venous conduit, thereby potentially reducing the benefit of this mode of revascularization (3,4). The safety of surgical revascularization is also often limited by extensive patient comorbidities. Over the past 2 decades, endovascular approaches have therefore been increasingly used for patients with CLI (5). Collectively, we have observed the development of innovative techniques for the endovascular revascularization of patients with CLI, including new devices, creative approaches (pedal/tibial access), chronic total occlusion recanalization, angiosome-guided revascularization, and distal interventions into and through the pedal arch (6,7). These advances have substantially expanded the endovascular options for the treatment of complex infrainguinal occlusive disease and improved our ability to achieve straight-line blood flow to the foot to maximize the likelihood of limb salvage.
The expanding role of endovascular interventions for CLI has raised questions regarding the best initial approach to the revascularization of CLI patients. While many have adopted the “endovascular first” strategy, questions persist regarding the effectiveness and durability of endovascular therapies. To date, the BASIL (Bypass Versus Angioplasty in Severe Ischaemia of the Leg) study remains the only completed randomized clinical trial directly comparing angioplasty with surgical bypass for CLI (8). The BASIL study demonstrated that surgical revascularization was associated with higher rates of post-operative morbidity and mortality, greater hospital length of stay, and greater initial costs compared to endovascular therapy. Conversely, in a post hoc analysis after 2 years, there was improved amputation-free survival with surgical revascularization. This finding has led to the view that surgical bypass may be preferred in patients with CLI and a life expectancy greater than 2 years. It is important to remember, however, that the BASIL study compared only balloon angioplasty with surgical bypass and was completed prior to the development of many of the endovascular devices and techniques currently being used. Over the past decade, newer endovascular treatment strategies have provided higher procedural success rates, more complete revascularization, improved patency, and potentially improved amputation-free survival compared to balloon angioplasty alone (5,9–11).
Many of the unanswered questions regarding the optimal approach to CLI are being addressed by the National Heart, Lung, and Blood Institute–sponsored, multicenter, randomized BEST-CLI (Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischemia) trial (12). This ongoing trial is designed to compare treatment efficacy, functional outcomes, and cost in patients with CLI and infrainguinal PAD undergoing best open surgical or best endovascular revascularization. A total of 2,100 patients at 120 sites in the United States and Canada will be enrolled and randomized between surgical or endovascular therapy and followed for a minimum of 2 years after revascularization. All currently available endovascular therapies and all surgical bypass techniques and conduits will be allowed.
The BEST-CLI trial will hopefully be completed in 2017. Until that time, clinicians will continue to rely on the best available data to guide revascularization strategies for the management of CLI. Meaningful observational data has been forthcoming from large national databases (e.g., National Inpatient Sample, National Hospital Discharge Survey, Medicare Database). These large databases (“Big Data”) provide an important global picture of current treatment modalities and practice patterns as well as trends in clinical outcomes. Since 2006, there have been several Big Data analyses evaluating national trends in the management of patients with symptomatic PAD (13–17). Irrespective of the source, a consistent pattern has emerged with regard to the treatment and outcomes of patients admitted with symptomatic PAD. Amputation rates and overall mortality continue to decline, in association with a drop in the number of open surgical procedures and a rise in the number of endovascular procedures. Collectively, these studies report a 2- to 3-fold increase in endovascular procedures, a 35% to 67% reduction in open procedures, and a 27% to 38% reduction in major amputations (14–16).
In this issue of the Journal, Agarwal et al. (18) add to our understanding regarding outcomes of surgical and endovascular procedures for CLI from an analysis of 642,433 CLI hospitalizations from the National Inpatient Sample (2003 to 2011). Consistent with prior investigations, the authors demonstrated a significant reduction in the proportion of patients undergoing surgical revascularization (13.9% in 2008 to 8.8% in 2011) with a concomitant rise in endovascular revascularization during the same time period (5.1% to 11.0%). This was accompanied by a steady decline in the incidence of in-hospital mortality and major amputation. Endovascular therapy was associated with a shorter mean length of stay and reduced hospital costs, despite a similar rate of in-hospital major amputation. As the authors correctly point out, the decreasing amputation and mortality rates cannot be directly attributable to a rise in endovascular therapy, as these studies cannot provide causal conclusions. Numerous other factors can influence mortality and amputation rates, including better medical care, aggressive risk factor modification, and appropriate wound care (19,20). Still, these associations are powerful, hypothesis generating, and warrant further investigation.
Practitioners should be encouraged by the findings of the current investigation. Our patients are benefiting from the modern management of CLI. Mortality and major amputation rates are decreasing and more patients can be treated with minimally invasive endovascular procedures. Interventional devices and techniques continue to advance at a rapid pace. Whether the improving CLI outcomes can be explained by the growth of these endovascular therapies is yet to be proven. We await the results of the landmark BEST-CLI trial to provide clarity regarding this issue and to further clarify the future role of surgical versus endovascular revascularization. Regardless of the outcome, there is cause for optimism and an awareness that the BEST is yet to come.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Laird has served as a consultant or advisory board member for Bard Peripheral Vascular, Boston Scientific, Cordis, Medtronic, and Abbott Vascular; and has received research support from WL Gore. Dr. Armstrong has served as a consultant or advisory board member for Abbott Vascular, Boston Scientific, Medtronic, Merck, and Spectranetics. Dr. Singh has reported that he has no relationships relevant to the contents of this paper to disclose.
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