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Point/Counterpoint: Endo first for the treatment of infrainguinal PAD?

The BASIL study originally published in the Lancet in 2005 (366:1925-34) and subsequently reiterated in multiple publications proposes that an endovascular approach should be utilized as the first invasive treatment modality in patients with infrainguinal peripheral arterial disease whose life expectancy is less than 2 years. By contrast, those patients expected to live beyond 2 years usually should be offered bypass surgery first, especially where a vein is available as a conduit. However, as can be seen from this month’s Point/Counterpoint by Dr. George Meier III and Dr. Michael S. Conte, the debate still rages as to the benefit of open vs. endovascular procedures for these patients. We encourage readers to voice their opinions in our “Letters to the Editor” section, as well as by participating in our web-based Quick Poll to the right of this story.
  - Dr. Russell Samson, Medical Editor, Vascular Specialist

POINT/COUNTERPOINT

Yes, endo is generally the way to go.

By Dr. George  Meier III

Endovascular treatment of lower-extremity arterial disease has rapidly expanded, now approaching the standard for treatment of patients with lower-extremity disease. While open bypass remains a gold standard for the clinical treatment of limb-threatening ischemia, there are many limitations to the use of open surgery.

First and foremost, open surgical intervention represents pain and suffering for the patient as well as a delayed recovery, compared with endovascular treatment. All other factors being equal, most patients would prefer a less-invasive approach to minimize these factors and to maximize the speed of recovery. Open surgical interventions typically require 6 weeks or longer to get back to a functional status even remotely close to the patient’s initial level of function. With more severe tissue loss or with greater pain preoperatively, the difficulty of getting the patient back to full functional status remains problematic. In John Porter’s classic paper published in the Journal of Vascular Surgery in 1998,1 wound complications occurred in 24% of the patients with a 5-year survival rate of only 49% in this relatively young population, average age 66 years. Repeat operations to maintain graft patency, treat wound complications, or treat recurrent or contralateral ischemia were required in 54% of the patients and 23% ultimately required major limb amputation.

Of the 112 patients in this study, only 14.3% achieved the ideal surgical result of an uncomplicated operation: long-term symptom relief, maintenance of functional status, and no recurrence or repeat operations. These are sobering statistics for anyone facing open revascularization for critical limb ischemia.

The BASIL trial is often put forward as an example of the best data available currently to define patient treatments in patients with critical limb ischemia.2 Despite this, BASIL was a flawed trial from the beginning because of the difficulties of truly randomizing patients with vascular disease to open surgical treatment vs. percutaneous treatment. First, all patients had to be appropriate candidates for both open and endovascular treatment. In the real world, we readily recognize that the luxury of this choice is not available to many of our patients. A lack of conduit or increased surgical risk results in endovascular treatment being the only management option for many. Additionally, patient preference increasingly plays a role in treatment selection, obviously increasing the likelihood of less invasive percutaneous treatment. Yes, the mortality of open bypass in BASIL is reported to be in the 1%-3% range, but this population has been carefully selected based on screening and treatment of underlying cardiac disease. The true incidence of cardiovascular disease is impossible to determine since significant cardiac disease negated randomization.

Unfortunately, even with all of the advances in endovascular treatments the results of percutaneous treatment have never reached the results of open bypass. Nonetheless, while the success may not be as great the risks are not as high either. The main challenge to endovascular treatment is the durability of the intervention. While we can usually treat pre-existing disease in the lower-extremity arterial tree, maintaining patency and durability is the challenge. As my esteemed colleague has noted, failure of endovascular treatment in the BASIL trial resulted in significantly worse outcomes for open bypass in those patients. While much was made about this fact when the BASIL trial was published, endovascular treatment after open failure has even a worse outcome than did open treatment after endovascular failure. The truth of the matter is that, for obvious reasons, failure begets failure.

Generally, there are two imaging approaches to defining the extent of vascular disease: first, contrast angiography via percutaneous access; and second, CT angiography using intravenous contrast. If contrast angiography is undertaken to diagnose the extent of disease, then it is a relatively limited extrapolation to treat the patient’s disease percutaneously at the time of the diagnostic angiogram. For this reason, I discuss with all patients coming for diagnostic angiography the issue of endovascular treatment. It is rare that we make patients worse with an attempt at endovascular treatment by an experienced interventionalist. Similarly, it is rare that we alter a bypass level based on an attempt at endovascular treatment. If, in my opinion, the risk of an attempted endovascular treatment is acceptable, then this is done at the time of the diagnostic angiogram. Patients appreciate this discussion prior to proceeding with diagnostic angiography.

 

 

What about inadequate autogenous conduit? Even my counterpoint opponent has published a documented 20% risk of absent or inadequate ipsilateral greater saphenous vein.3 While he and his colleagues have documented excellent results using contralateral greater saphenous vein, there is still an inevitable morbidity and, yes, even a mortality risk associated with contralateral leg vein harvest. While in a good cardiac risk patient this may be negligible, we are again facing an ever more complex and medically ill patient population to subject to vascular treatment. It is in this setting that many vascular surgeons move to prosthetic conduits for the treatment of the patient’s vascular disease. While this may provide a short-term fix for the conduit problem, in the long term the risk of sudden, uncompensated failure of limb perfusion by prosthetic graft failure may often result in a higher risk procedure at a time when the patient may be older and more severely limited. Endovascular treatment is clearly a reasonable alternative in patients where autogenous conduit is not readily available.

While this debate will inevitably continue as long as practitioners have bias toward either open or endovascular management of vascular disease, one thing is for certain: We will continue to extend the limits of treatment to ever more ill and complex patients. While we have been very successful at performing fewer and fewer morbid interventions for limb-threatening vascular disease, these patients continue to be increasingly challenging to manage.

As the overall population continues to age, the need for less invasive treatment of limb-threatening vascular disease will continue to grow. And, yes, I agree that vascular surgeons in the role of interventionalist or surgeon are the leadership for the management of CLI in the future.

Dr. Meier is professor and chief of vascular surgery at the University of Cincinnati.

References

1. J. Vasc. Surg. 1998;27:256-63; discussion 264-6

2. Lancet 2005;366:1925-34

3. J. Vasc. Surg. 2002:35:1085-92

No: A selective approach remains the key.

By Dr. MICHAEL S. CONTE

Recently the term “pandemic” has been applied to the growing global impact of peripheral artery disease (PAD), currently estimated to afflict more than 200 million individuals.1 The term “critical limb ischemia” (CLI), connoting the most advanced stage of PAD with imminent limb threat, is inadequately defined2 but likely encompasses 1%-3% of PAD. Aging of the global population and the increasing prevalence of diabetes are fueling increases in CLI and its impact on public health. While traditionally treated largely by vascular surgeons plying the open bypass trade, the ongoing development and market dispersion of catheter-based technologies for CLI has led to major secular changes.

Recent estimates suggest that upward of 5 billion dollars are spent annually on CLI in the Medicare population.3, 4 Increasing volumes and costs associated with revascularizations for CLI are a major driver, yet recent data suggest that regional spending in the United States is widely disparate and not directly associated with amputation rates.5 Thus defining effectiveness and value in CLI care has become a major challenge to the vascular community.

In current everyday practice, clinicians are faced with making treatment choices for CLI patients based on limited data and lots of anecdote. While the “open vs. endo” debate goes on, in many ways it has become less broadly relevant as the sophisticated clinician recognizes the real challenge lies in defining which approach to apply first in the right patient, at the right time. The only randomized, controlled trial (RCT) done in the field, the BASIL trial,6 is more than a decade old. However its findings remain important. For patients with “severe limb ischemia” likely to survive for at least 2 years, open bypass surgery offered better outcomes over angioplasty as an initial strategy.7 Moreover, the finding in BASIL that patients undergoing bypass after prior failed angioplasty did poorly,8 suggesting “no free lunch” for endovascular failures, has since been confirmed in other large registry studies.9

Simply stated, failure matters in CLI. And although endovascular techniques have continued to improve, the growing epidemic of restenosis shows no signs of abating.10 As in the case of percutaneous coronary intervention (PCI), we will know when endo results are meaningfully improved in PAD when the procedure volume curves actually flatten, not continue to grow geometrically.

So, in selecting the optimal strategy for CLI today, let’s focus on what we seem to know and try to apply an evidence-based mentality. We know that open bypass surgery is an effective and versatile treatment, but one that carries real morbidity (10%-20%) and some mortality (1%-3%). Among many large studies, the PREVENT III multicenter trial provides benchmark data on perioperative and 1-year outcomes.11

 

 

We know that the quality of the vein is the critical technical determinant of success, and arterial anatomy is less influential as long as there is outflow to the foot.12 We know that poor quality veins, prosthetics, and other alternatives are much inferior in CLI. And we know that there is a subset of CLI patients who are at high risk for adverse surgical outcomes.13, 14 However one defines them, up to 10% of patients in the large surgical series are in a high-risk group and may not experience meaningful benefit. For endovascular treatments, the data are less clear but certain trends have been consistent. Multilevel disease, long-segment occlusions, heavily calcified lesions, and more advanced tissue loss are negative predictors of clinical success.

Thus at first glance the weaknesses of the two strategies are largely complementary.15 When I encounter an average-risk CLI patient, with an adequate saphenous vein and more than one unfavorable endo factor, I am inclined towards bypass first.

Conversely, endo-favorable anatomy in higher risk patients is a no-brainer. Lots of people fall in the middle, and a significant minority should be considered for primary amputation. Currently my practice is roughly 50% bypass surgery-first in CLI.

Endovascular innovations have made a huge impact on vascular practice, and the leadership of many vascular surgeons (e.g., my esteemed counterpoint author) has been central to advancing the field. Better wires and catheters, retrograde approaches, and drug-eluting technologies continue to be developed at a dizzying pace.

We are all continually learning. Unfortunately, we lack good objective evidence to support most of the expanding armamentarium for CLI. However it is abundantly clear that technical (angiographic) success and clinical success are far apart, which is no surprise. What is surprising is an unsettlingly common lack of honesty about such an obvious fact. Are we all guilty of looking through rose-colored glasses?

Is it really such big news that patency actually matters for most patients with CLI? Technologies will not improve quickly enough if there is no market imperative to make them better. If we continue to buy and use things that are frequently ineffective, or don’t measure it carefully, where is the motivation?

No matter the lens through which one looks at the CLI field, it is desperate for improvement. We need much better technologies that provide longer lasting solutions for patients. We need better diagnostics to predict disease progression and responses to treatment.

We need some new medical or biological therapies that truly alleviate suffering. And we largely lack data on comparative effectiveness, and value, to support thoughtful application of our current treatment arsenal.

Most importantly what we need now is less dogma, and a lot more science. Over more than two decades, multiple RCTs comparing medical, interventional and surgical therapies for coronary artery disease have formed the basis for practice guidelines.

By comparison, our field is nearly incoherent both to vascular specialists and referring physicians. It will not be easy, but this can be done in PAD as well, and the vascular community must embrace it. Moreover it is imperative that vascular surgeons help to lead these multidisciplinary efforts, and develop evidence-based global guidelines to guide best practice in CLI.16 The recent funding of the BEST-CLI trial in the United States and the BASIL-2 trial in the United Kingdom demonstrate the importance to public health and offer great opportunities.

Until better evidence is available, a rational approach to limb salvage requires flexibility, understanding of the factors predicting success/failure for each modality, and the continued use of open bypass surgery as the initial treatment option for a significant number of patients.

And for the sake of our most vulnerable patients, we better keep training vascular surgeons to do all of it well.

Dr. Conte is professor and chief, division of vascular & endovascular surgery and the Edwin J. Wylie, M.D. Chair in Vascular Surgery at the University of California, San Francisco.

References

1. Lancet 2013;382:1329-40

2. J. Vasc. Surg. 2014;59:220-34

3. Vasc Med. 2008;13:209-15

4. Circulation 2010;3:642-51

5. JAMA Surg. 2014;149:34-42

6. Lancet 2005;366:1925-34

7. J. Vasc. Surg. 2010;51:5S-17S

8. J. Vasc. Surg. 2010;51:18S-31S

9. J. Vasc. Surg. 2011;54:730-6

10. J. Amer. Heart Assoc. 2013;2:e000345

11. J. Vasc. Surg. 2006;43:742-51

12. J. Vasc. Surg. 2007;46:1180-90

13. J. Vasc. Surg. 2009;50:769-75

14. J. Vasc. Surg. 2010;52:1218-25

15. J. Vasc. Surg. 2013;57:8S-13S16. J. Vasc. Surg. 2014;59:510

References

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The BASIL study originally published in the Lancet in 2005 (366:1925-34) and subsequently reiterated in multiple publications proposes that an endovascular approach should be utilized as the first invasive treatment modality in patients with infrainguinal peripheral arterial disease whose life expectancy is less than 2 years. By contrast, those patients expected to live beyond 2 years usually should be offered bypass surgery first, especially where a vein is available as a conduit. However, as can be seen from this month’s Point/Counterpoint by Dr. George Meier III and Dr. Michael S. Conte, the debate still rages as to the benefit of open vs. endovascular procedures for these patients. We encourage readers to voice their opinions in our “Letters to the Editor” section, as well as by participating in our web-based Quick Poll to the right of this story.
  - Dr. Russell Samson, Medical Editor, Vascular Specialist

POINT/COUNTERPOINT

Yes, endo is generally the way to go.

By Dr. George  Meier III

Endovascular treatment of lower-extremity arterial disease has rapidly expanded, now approaching the standard for treatment of patients with lower-extremity disease. While open bypass remains a gold standard for the clinical treatment of limb-threatening ischemia, there are many limitations to the use of open surgery.

First and foremost, open surgical intervention represents pain and suffering for the patient as well as a delayed recovery, compared with endovascular treatment. All other factors being equal, most patients would prefer a less-invasive approach to minimize these factors and to maximize the speed of recovery. Open surgical interventions typically require 6 weeks or longer to get back to a functional status even remotely close to the patient’s initial level of function. With more severe tissue loss or with greater pain preoperatively, the difficulty of getting the patient back to full functional status remains problematic. In John Porter’s classic paper published in the Journal of Vascular Surgery in 1998,1 wound complications occurred in 24% of the patients with a 5-year survival rate of only 49% in this relatively young population, average age 66 years. Repeat operations to maintain graft patency, treat wound complications, or treat recurrent or contralateral ischemia were required in 54% of the patients and 23% ultimately required major limb amputation.

Of the 112 patients in this study, only 14.3% achieved the ideal surgical result of an uncomplicated operation: long-term symptom relief, maintenance of functional status, and no recurrence or repeat operations. These are sobering statistics for anyone facing open revascularization for critical limb ischemia.

The BASIL trial is often put forward as an example of the best data available currently to define patient treatments in patients with critical limb ischemia.2 Despite this, BASIL was a flawed trial from the beginning because of the difficulties of truly randomizing patients with vascular disease to open surgical treatment vs. percutaneous treatment. First, all patients had to be appropriate candidates for both open and endovascular treatment. In the real world, we readily recognize that the luxury of this choice is not available to many of our patients. A lack of conduit or increased surgical risk results in endovascular treatment being the only management option for many. Additionally, patient preference increasingly plays a role in treatment selection, obviously increasing the likelihood of less invasive percutaneous treatment. Yes, the mortality of open bypass in BASIL is reported to be in the 1%-3% range, but this population has been carefully selected based on screening and treatment of underlying cardiac disease. The true incidence of cardiovascular disease is impossible to determine since significant cardiac disease negated randomization.

Unfortunately, even with all of the advances in endovascular treatments the results of percutaneous treatment have never reached the results of open bypass. Nonetheless, while the success may not be as great the risks are not as high either. The main challenge to endovascular treatment is the durability of the intervention. While we can usually treat pre-existing disease in the lower-extremity arterial tree, maintaining patency and durability is the challenge. As my esteemed colleague has noted, failure of endovascular treatment in the BASIL trial resulted in significantly worse outcomes for open bypass in those patients. While much was made about this fact when the BASIL trial was published, endovascular treatment after open failure has even a worse outcome than did open treatment after endovascular failure. The truth of the matter is that, for obvious reasons, failure begets failure.

Generally, there are two imaging approaches to defining the extent of vascular disease: first, contrast angiography via percutaneous access; and second, CT angiography using intravenous contrast. If contrast angiography is undertaken to diagnose the extent of disease, then it is a relatively limited extrapolation to treat the patient’s disease percutaneously at the time of the diagnostic angiogram. For this reason, I discuss with all patients coming for diagnostic angiography the issue of endovascular treatment. It is rare that we make patients worse with an attempt at endovascular treatment by an experienced interventionalist. Similarly, it is rare that we alter a bypass level based on an attempt at endovascular treatment. If, in my opinion, the risk of an attempted endovascular treatment is acceptable, then this is done at the time of the diagnostic angiogram. Patients appreciate this discussion prior to proceeding with diagnostic angiography.

 

 

What about inadequate autogenous conduit? Even my counterpoint opponent has published a documented 20% risk of absent or inadequate ipsilateral greater saphenous vein.3 While he and his colleagues have documented excellent results using contralateral greater saphenous vein, there is still an inevitable morbidity and, yes, even a mortality risk associated with contralateral leg vein harvest. While in a good cardiac risk patient this may be negligible, we are again facing an ever more complex and medically ill patient population to subject to vascular treatment. It is in this setting that many vascular surgeons move to prosthetic conduits for the treatment of the patient’s vascular disease. While this may provide a short-term fix for the conduit problem, in the long term the risk of sudden, uncompensated failure of limb perfusion by prosthetic graft failure may often result in a higher risk procedure at a time when the patient may be older and more severely limited. Endovascular treatment is clearly a reasonable alternative in patients where autogenous conduit is not readily available.

While this debate will inevitably continue as long as practitioners have bias toward either open or endovascular management of vascular disease, one thing is for certain: We will continue to extend the limits of treatment to ever more ill and complex patients. While we have been very successful at performing fewer and fewer morbid interventions for limb-threatening vascular disease, these patients continue to be increasingly challenging to manage.

As the overall population continues to age, the need for less invasive treatment of limb-threatening vascular disease will continue to grow. And, yes, I agree that vascular surgeons in the role of interventionalist or surgeon are the leadership for the management of CLI in the future.

Dr. Meier is professor and chief of vascular surgery at the University of Cincinnati.

References

1. J. Vasc. Surg. 1998;27:256-63; discussion 264-6

2. Lancet 2005;366:1925-34

3. J. Vasc. Surg. 2002:35:1085-92

No: A selective approach remains the key.

By Dr. MICHAEL S. CONTE

Recently the term “pandemic” has been applied to the growing global impact of peripheral artery disease (PAD), currently estimated to afflict more than 200 million individuals.1 The term “critical limb ischemia” (CLI), connoting the most advanced stage of PAD with imminent limb threat, is inadequately defined2 but likely encompasses 1%-3% of PAD. Aging of the global population and the increasing prevalence of diabetes are fueling increases in CLI and its impact on public health. While traditionally treated largely by vascular surgeons plying the open bypass trade, the ongoing development and market dispersion of catheter-based technologies for CLI has led to major secular changes.

Recent estimates suggest that upward of 5 billion dollars are spent annually on CLI in the Medicare population.3, 4 Increasing volumes and costs associated with revascularizations for CLI are a major driver, yet recent data suggest that regional spending in the United States is widely disparate and not directly associated with amputation rates.5 Thus defining effectiveness and value in CLI care has become a major challenge to the vascular community.

In current everyday practice, clinicians are faced with making treatment choices for CLI patients based on limited data and lots of anecdote. While the “open vs. endo” debate goes on, in many ways it has become less broadly relevant as the sophisticated clinician recognizes the real challenge lies in defining which approach to apply first in the right patient, at the right time. The only randomized, controlled trial (RCT) done in the field, the BASIL trial,6 is more than a decade old. However its findings remain important. For patients with “severe limb ischemia” likely to survive for at least 2 years, open bypass surgery offered better outcomes over angioplasty as an initial strategy.7 Moreover, the finding in BASIL that patients undergoing bypass after prior failed angioplasty did poorly,8 suggesting “no free lunch” for endovascular failures, has since been confirmed in other large registry studies.9

Simply stated, failure matters in CLI. And although endovascular techniques have continued to improve, the growing epidemic of restenosis shows no signs of abating.10 As in the case of percutaneous coronary intervention (PCI), we will know when endo results are meaningfully improved in PAD when the procedure volume curves actually flatten, not continue to grow geometrically.

So, in selecting the optimal strategy for CLI today, let’s focus on what we seem to know and try to apply an evidence-based mentality. We know that open bypass surgery is an effective and versatile treatment, but one that carries real morbidity (10%-20%) and some mortality (1%-3%). Among many large studies, the PREVENT III multicenter trial provides benchmark data on perioperative and 1-year outcomes.11

 

 

We know that the quality of the vein is the critical technical determinant of success, and arterial anatomy is less influential as long as there is outflow to the foot.12 We know that poor quality veins, prosthetics, and other alternatives are much inferior in CLI. And we know that there is a subset of CLI patients who are at high risk for adverse surgical outcomes.13, 14 However one defines them, up to 10% of patients in the large surgical series are in a high-risk group and may not experience meaningful benefit. For endovascular treatments, the data are less clear but certain trends have been consistent. Multilevel disease, long-segment occlusions, heavily calcified lesions, and more advanced tissue loss are negative predictors of clinical success.

Thus at first glance the weaknesses of the two strategies are largely complementary.15 When I encounter an average-risk CLI patient, with an adequate saphenous vein and more than one unfavorable endo factor, I am inclined towards bypass first.

Conversely, endo-favorable anatomy in higher risk patients is a no-brainer. Lots of people fall in the middle, and a significant minority should be considered for primary amputation. Currently my practice is roughly 50% bypass surgery-first in CLI.

Endovascular innovations have made a huge impact on vascular practice, and the leadership of many vascular surgeons (e.g., my esteemed counterpoint author) has been central to advancing the field. Better wires and catheters, retrograde approaches, and drug-eluting technologies continue to be developed at a dizzying pace.

We are all continually learning. Unfortunately, we lack good objective evidence to support most of the expanding armamentarium for CLI. However it is abundantly clear that technical (angiographic) success and clinical success are far apart, which is no surprise. What is surprising is an unsettlingly common lack of honesty about such an obvious fact. Are we all guilty of looking through rose-colored glasses?

Is it really such big news that patency actually matters for most patients with CLI? Technologies will not improve quickly enough if there is no market imperative to make them better. If we continue to buy and use things that are frequently ineffective, or don’t measure it carefully, where is the motivation?

No matter the lens through which one looks at the CLI field, it is desperate for improvement. We need much better technologies that provide longer lasting solutions for patients. We need better diagnostics to predict disease progression and responses to treatment.

We need some new medical or biological therapies that truly alleviate suffering. And we largely lack data on comparative effectiveness, and value, to support thoughtful application of our current treatment arsenal.

Most importantly what we need now is less dogma, and a lot more science. Over more than two decades, multiple RCTs comparing medical, interventional and surgical therapies for coronary artery disease have formed the basis for practice guidelines.

By comparison, our field is nearly incoherent both to vascular specialists and referring physicians. It will not be easy, but this can be done in PAD as well, and the vascular community must embrace it. Moreover it is imperative that vascular surgeons help to lead these multidisciplinary efforts, and develop evidence-based global guidelines to guide best practice in CLI.16 The recent funding of the BEST-CLI trial in the United States and the BASIL-2 trial in the United Kingdom demonstrate the importance to public health and offer great opportunities.

Until better evidence is available, a rational approach to limb salvage requires flexibility, understanding of the factors predicting success/failure for each modality, and the continued use of open bypass surgery as the initial treatment option for a significant number of patients.

And for the sake of our most vulnerable patients, we better keep training vascular surgeons to do all of it well.

Dr. Conte is professor and chief, division of vascular & endovascular surgery and the Edwin J. Wylie, M.D. Chair in Vascular Surgery at the University of California, San Francisco.

References

1. Lancet 2013;382:1329-40

2. J. Vasc. Surg. 2014;59:220-34

3. Vasc Med. 2008;13:209-15

4. Circulation 2010;3:642-51

5. JAMA Surg. 2014;149:34-42

6. Lancet 2005;366:1925-34

7. J. Vasc. Surg. 2010;51:5S-17S

8. J. Vasc. Surg. 2010;51:18S-31S

9. J. Vasc. Surg. 2011;54:730-6

10. J. Amer. Heart Assoc. 2013;2:e000345

11. J. Vasc. Surg. 2006;43:742-51

12. J. Vasc. Surg. 2007;46:1180-90

13. J. Vasc. Surg. 2009;50:769-75

14. J. Vasc. Surg. 2010;52:1218-25

15. J. Vasc. Surg. 2013;57:8S-13S16. J. Vasc. Surg. 2014;59:510

The BASIL study originally published in the Lancet in 2005 (366:1925-34) and subsequently reiterated in multiple publications proposes that an endovascular approach should be utilized as the first invasive treatment modality in patients with infrainguinal peripheral arterial disease whose life expectancy is less than 2 years. By contrast, those patients expected to live beyond 2 years usually should be offered bypass surgery first, especially where a vein is available as a conduit. However, as can be seen from this month’s Point/Counterpoint by Dr. George Meier III and Dr. Michael S. Conte, the debate still rages as to the benefit of open vs. endovascular procedures for these patients. We encourage readers to voice their opinions in our “Letters to the Editor” section, as well as by participating in our web-based Quick Poll to the right of this story.
  - Dr. Russell Samson, Medical Editor, Vascular Specialist

POINT/COUNTERPOINT

Yes, endo is generally the way to go.

By Dr. George  Meier III

Endovascular treatment of lower-extremity arterial disease has rapidly expanded, now approaching the standard for treatment of patients with lower-extremity disease. While open bypass remains a gold standard for the clinical treatment of limb-threatening ischemia, there are many limitations to the use of open surgery.

First and foremost, open surgical intervention represents pain and suffering for the patient as well as a delayed recovery, compared with endovascular treatment. All other factors being equal, most patients would prefer a less-invasive approach to minimize these factors and to maximize the speed of recovery. Open surgical interventions typically require 6 weeks or longer to get back to a functional status even remotely close to the patient’s initial level of function. With more severe tissue loss or with greater pain preoperatively, the difficulty of getting the patient back to full functional status remains problematic. In John Porter’s classic paper published in the Journal of Vascular Surgery in 1998,1 wound complications occurred in 24% of the patients with a 5-year survival rate of only 49% in this relatively young population, average age 66 years. Repeat operations to maintain graft patency, treat wound complications, or treat recurrent or contralateral ischemia were required in 54% of the patients and 23% ultimately required major limb amputation.

Of the 112 patients in this study, only 14.3% achieved the ideal surgical result of an uncomplicated operation: long-term symptom relief, maintenance of functional status, and no recurrence or repeat operations. These are sobering statistics for anyone facing open revascularization for critical limb ischemia.

The BASIL trial is often put forward as an example of the best data available currently to define patient treatments in patients with critical limb ischemia.2 Despite this, BASIL was a flawed trial from the beginning because of the difficulties of truly randomizing patients with vascular disease to open surgical treatment vs. percutaneous treatment. First, all patients had to be appropriate candidates for both open and endovascular treatment. In the real world, we readily recognize that the luxury of this choice is not available to many of our patients. A lack of conduit or increased surgical risk results in endovascular treatment being the only management option for many. Additionally, patient preference increasingly plays a role in treatment selection, obviously increasing the likelihood of less invasive percutaneous treatment. Yes, the mortality of open bypass in BASIL is reported to be in the 1%-3% range, but this population has been carefully selected based on screening and treatment of underlying cardiac disease. The true incidence of cardiovascular disease is impossible to determine since significant cardiac disease negated randomization.

Unfortunately, even with all of the advances in endovascular treatments the results of percutaneous treatment have never reached the results of open bypass. Nonetheless, while the success may not be as great the risks are not as high either. The main challenge to endovascular treatment is the durability of the intervention. While we can usually treat pre-existing disease in the lower-extremity arterial tree, maintaining patency and durability is the challenge. As my esteemed colleague has noted, failure of endovascular treatment in the BASIL trial resulted in significantly worse outcomes for open bypass in those patients. While much was made about this fact when the BASIL trial was published, endovascular treatment after open failure has even a worse outcome than did open treatment after endovascular failure. The truth of the matter is that, for obvious reasons, failure begets failure.

Generally, there are two imaging approaches to defining the extent of vascular disease: first, contrast angiography via percutaneous access; and second, CT angiography using intravenous contrast. If contrast angiography is undertaken to diagnose the extent of disease, then it is a relatively limited extrapolation to treat the patient’s disease percutaneously at the time of the diagnostic angiogram. For this reason, I discuss with all patients coming for diagnostic angiography the issue of endovascular treatment. It is rare that we make patients worse with an attempt at endovascular treatment by an experienced interventionalist. Similarly, it is rare that we alter a bypass level based on an attempt at endovascular treatment. If, in my opinion, the risk of an attempted endovascular treatment is acceptable, then this is done at the time of the diagnostic angiogram. Patients appreciate this discussion prior to proceeding with diagnostic angiography.

 

 

What about inadequate autogenous conduit? Even my counterpoint opponent has published a documented 20% risk of absent or inadequate ipsilateral greater saphenous vein.3 While he and his colleagues have documented excellent results using contralateral greater saphenous vein, there is still an inevitable morbidity and, yes, even a mortality risk associated with contralateral leg vein harvest. While in a good cardiac risk patient this may be negligible, we are again facing an ever more complex and medically ill patient population to subject to vascular treatment. It is in this setting that many vascular surgeons move to prosthetic conduits for the treatment of the patient’s vascular disease. While this may provide a short-term fix for the conduit problem, in the long term the risk of sudden, uncompensated failure of limb perfusion by prosthetic graft failure may often result in a higher risk procedure at a time when the patient may be older and more severely limited. Endovascular treatment is clearly a reasonable alternative in patients where autogenous conduit is not readily available.

While this debate will inevitably continue as long as practitioners have bias toward either open or endovascular management of vascular disease, one thing is for certain: We will continue to extend the limits of treatment to ever more ill and complex patients. While we have been very successful at performing fewer and fewer morbid interventions for limb-threatening vascular disease, these patients continue to be increasingly challenging to manage.

As the overall population continues to age, the need for less invasive treatment of limb-threatening vascular disease will continue to grow. And, yes, I agree that vascular surgeons in the role of interventionalist or surgeon are the leadership for the management of CLI in the future.

Dr. Meier is professor and chief of vascular surgery at the University of Cincinnati.

References

1. J. Vasc. Surg. 1998;27:256-63; discussion 264-6

2. Lancet 2005;366:1925-34

3. J. Vasc. Surg. 2002:35:1085-92

No: A selective approach remains the key.

By Dr. MICHAEL S. CONTE

Recently the term “pandemic” has been applied to the growing global impact of peripheral artery disease (PAD), currently estimated to afflict more than 200 million individuals.1 The term “critical limb ischemia” (CLI), connoting the most advanced stage of PAD with imminent limb threat, is inadequately defined2 but likely encompasses 1%-3% of PAD. Aging of the global population and the increasing prevalence of diabetes are fueling increases in CLI and its impact on public health. While traditionally treated largely by vascular surgeons plying the open bypass trade, the ongoing development and market dispersion of catheter-based technologies for CLI has led to major secular changes.

Recent estimates suggest that upward of 5 billion dollars are spent annually on CLI in the Medicare population.3, 4 Increasing volumes and costs associated with revascularizations for CLI are a major driver, yet recent data suggest that regional spending in the United States is widely disparate and not directly associated with amputation rates.5 Thus defining effectiveness and value in CLI care has become a major challenge to the vascular community.

In current everyday practice, clinicians are faced with making treatment choices for CLI patients based on limited data and lots of anecdote. While the “open vs. endo” debate goes on, in many ways it has become less broadly relevant as the sophisticated clinician recognizes the real challenge lies in defining which approach to apply first in the right patient, at the right time. The only randomized, controlled trial (RCT) done in the field, the BASIL trial,6 is more than a decade old. However its findings remain important. For patients with “severe limb ischemia” likely to survive for at least 2 years, open bypass surgery offered better outcomes over angioplasty as an initial strategy.7 Moreover, the finding in BASIL that patients undergoing bypass after prior failed angioplasty did poorly,8 suggesting “no free lunch” for endovascular failures, has since been confirmed in other large registry studies.9

Simply stated, failure matters in CLI. And although endovascular techniques have continued to improve, the growing epidemic of restenosis shows no signs of abating.10 As in the case of percutaneous coronary intervention (PCI), we will know when endo results are meaningfully improved in PAD when the procedure volume curves actually flatten, not continue to grow geometrically.

So, in selecting the optimal strategy for CLI today, let’s focus on what we seem to know and try to apply an evidence-based mentality. We know that open bypass surgery is an effective and versatile treatment, but one that carries real morbidity (10%-20%) and some mortality (1%-3%). Among many large studies, the PREVENT III multicenter trial provides benchmark data on perioperative and 1-year outcomes.11

 

 

We know that the quality of the vein is the critical technical determinant of success, and arterial anatomy is less influential as long as there is outflow to the foot.12 We know that poor quality veins, prosthetics, and other alternatives are much inferior in CLI. And we know that there is a subset of CLI patients who are at high risk for adverse surgical outcomes.13, 14 However one defines them, up to 10% of patients in the large surgical series are in a high-risk group and may not experience meaningful benefit. For endovascular treatments, the data are less clear but certain trends have been consistent. Multilevel disease, long-segment occlusions, heavily calcified lesions, and more advanced tissue loss are negative predictors of clinical success.

Thus at first glance the weaknesses of the two strategies are largely complementary.15 When I encounter an average-risk CLI patient, with an adequate saphenous vein and more than one unfavorable endo factor, I am inclined towards bypass first.

Conversely, endo-favorable anatomy in higher risk patients is a no-brainer. Lots of people fall in the middle, and a significant minority should be considered for primary amputation. Currently my practice is roughly 50% bypass surgery-first in CLI.

Endovascular innovations have made a huge impact on vascular practice, and the leadership of many vascular surgeons (e.g., my esteemed counterpoint author) has been central to advancing the field. Better wires and catheters, retrograde approaches, and drug-eluting technologies continue to be developed at a dizzying pace.

We are all continually learning. Unfortunately, we lack good objective evidence to support most of the expanding armamentarium for CLI. However it is abundantly clear that technical (angiographic) success and clinical success are far apart, which is no surprise. What is surprising is an unsettlingly common lack of honesty about such an obvious fact. Are we all guilty of looking through rose-colored glasses?

Is it really such big news that patency actually matters for most patients with CLI? Technologies will not improve quickly enough if there is no market imperative to make them better. If we continue to buy and use things that are frequently ineffective, or don’t measure it carefully, where is the motivation?

No matter the lens through which one looks at the CLI field, it is desperate for improvement. We need much better technologies that provide longer lasting solutions for patients. We need better diagnostics to predict disease progression and responses to treatment.

We need some new medical or biological therapies that truly alleviate suffering. And we largely lack data on comparative effectiveness, and value, to support thoughtful application of our current treatment arsenal.

Most importantly what we need now is less dogma, and a lot more science. Over more than two decades, multiple RCTs comparing medical, interventional and surgical therapies for coronary artery disease have formed the basis for practice guidelines.

By comparison, our field is nearly incoherent both to vascular specialists and referring physicians. It will not be easy, but this can be done in PAD as well, and the vascular community must embrace it. Moreover it is imperative that vascular surgeons help to lead these multidisciplinary efforts, and develop evidence-based global guidelines to guide best practice in CLI.16 The recent funding of the BEST-CLI trial in the United States and the BASIL-2 trial in the United Kingdom demonstrate the importance to public health and offer great opportunities.

Until better evidence is available, a rational approach to limb salvage requires flexibility, understanding of the factors predicting success/failure for each modality, and the continued use of open bypass surgery as the initial treatment option for a significant number of patients.

And for the sake of our most vulnerable patients, we better keep training vascular surgeons to do all of it well.

Dr. Conte is professor and chief, division of vascular & endovascular surgery and the Edwin J. Wylie, M.D. Chair in Vascular Surgery at the University of California, San Francisco.

References

1. Lancet 2013;382:1329-40

2. J. Vasc. Surg. 2014;59:220-34

3. Vasc Med. 2008;13:209-15

4. Circulation 2010;3:642-51

5. JAMA Surg. 2014;149:34-42

6. Lancet 2005;366:1925-34

7. J. Vasc. Surg. 2010;51:5S-17S

8. J. Vasc. Surg. 2010;51:18S-31S

9. J. Vasc. Surg. 2011;54:730-6

10. J. Amer. Heart Assoc. 2013;2:e000345

11. J. Vasc. Surg. 2006;43:742-51

12. J. Vasc. Surg. 2007;46:1180-90

13. J. Vasc. Surg. 2009;50:769-75

14. J. Vasc. Surg. 2010;52:1218-25

15. J. Vasc. Surg. 2013;57:8S-13S16. J. Vasc. Surg. 2014;59:510

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Point/Counterpoint: Endo first for the treatment of infrainguinal PAD?
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