Balloon Angioplasty or Nitinol Stents for Peripheral-Artery Disease
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Schillinger et al. (May 4 issue)1 demonstrated the superiority of primary stenting with nitinol stents, as compared with balloon angioplasty, in patients with peripheral-artery disease. However, the findings raise an issue with regard to the treatment of restenosis. Endovascular treatment usually represents the second treatment option, after medical therapy and before final surgical revascularization. Restenosis of the target vessel after balloon angioplasty can be treated initially with repeated balloon angioplasty and, in subsequent recurrences, with stenting. In the meantime, the patient has months or years of freedom from symptoms without being treated with stents. In contrast, the reimplantation of a stent to treat restenosis after stenting is much more problematic, and the patient is more likely to require surgical revascularization. Patients with peripheral-artery disease should be offered therapeutic alternatives that will delay irreversible complications as long as possible. Even if balloon angioplasty is a less durable treatment option than nitinol stenting, we believe that it should be considered as the first step in the endovascular management of the disease.
Ilias Dalainas, M.D., Ph.D.
Giovanni Nano, M.D.
University of Milan
20097 Milan, Italy
hdlns@freemail.gr
References
Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006;354:1879-1888.
To the Editor: Schillinger et al. compared balloon angioplasty with the implantation of nitinol stents in the superficial femoral artery. The authors provided no information about the specific antihypertensive medications being taken by the study patients, particularly the number of patients who were taking angiotensin-converting–enzyme (ACE) inhibitors in each group. In a randomized trial, Ahimastos et al. demonstrated that treatment with an ACE inhibitor (ramipril) for 24 weeks increased the pain-free walking time and the maximum walking time in a clinically and statistically significant manner, as compared with current therapies in peripheral-artery disease.1 ACE inhibitors improve the flow of blood to the lower extremities in patients with peripheral-artery disease. The mechanisms include reduced levels of angiotensin II, improved endothelial function, sympathetic inhibition, angiogenesis (collateral formation), and regression of atherosclerosis.1
Ajit Kashyap, M.D.
Command Hospital (Central Command)
Lucknow 226 002, India
kashyapajits@yahoo.com
Kuldip Parkash Anand, M.D.
Command Hospital (Eastern Command)
Kolkata 700 027, India
Surekha Kashyap, M.D.
Command Headquarters (Central Command)
Lucknow 226 002, India
References
Ahimastos AA, Lawfer A, Reid CM, Blombery PA, Kingwell BA. Ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med 2006;144:660-664.
To the Editor: As outlined in the accompanying editorial by Hirsch, well-conducted trials that examine interventions for peripheral-artery disease are needed.1 Since the risk of limb loss is low during the long-term follow-up of patients with intermittent claudication, the primary objective of interventions is to improve the health-related quality of life.2 Although objective measures such as patency on imaging, ankle pressures, and the distance walked on treadmills provide important information about the results of interventions, they do not assess the patients' quality of life.3 A number of tools have been developed specifically to measure the quality of life in patients presenting with intermittent claudication.2,3,4 In this regard, it is disappointing that none of these measures were used by Schillinger and colleagues. Since we have no evidence to suggest that improved patency of lower-limb arteries has any definite benefit, it is important that we investigate the value of treatments for intermittent claudication in terms of the quality of life.
Jonathan Golledge, M.Chir.
James Cook University
Townsville, QLD 4811, Australia
jonathan.golledge@jcu.edu.au
Paul Norman, D.S.
University of Western Australia
Perth, WA 6959, Australia
References
Hirsch AT. Treatment of peripheral arterial disease -- extending "intervention" to "therapeutic choice." N Engl J Med 2006;354:1944-1947.
Golledge J, Askew C, Leicht A, Oldenburg B. Outcome assessment for intermittent claudication. Eur J Vasc Endovasc Surg 2006;31:44-45.
Mehta T, Venkata Subramaniam A, Chetter I, McCollum P. Assessing the validity and responsiveness of disease-specific quality of life instruments in intermittent claudication. Eur J Vasc Endovasc Surg 2006;31:46-52.
Chong PF, Garratt AM, Golledge J, Greenhalgh RM, Davies AH. The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure. J Vasc Surg 2002;36:764-771.
To the Editor: In the important study by Schillinger et al., it is curious that the rates of repeated intervention were similar in both the primary-stenting and provisional-stenting groups. It is also curious that the functional and anatomical end points were so discordant: the rate of angiographic restenosis and the distance walked on a treadmill were both improved dramatically in the stent group as compared with the angioplasty group, but ankle pressures and the rate of reocclusion were not significantly influenced by stenting.
One challenge in the analysis of studies of lower-extremity interventions is that patients generally have two legs. Contralateral, even symmetric, patterns of obstructive atherosclerosis are common, as are contralateral symptoms and treatments.1 Could the authors comment on the interaction of contralateral disease and interventions on the study end points, as well as how the treadmill data were reported or censored in relation to subsequent ipsilateral and contralateral invasive procedures?
Finally, even with the use of the strategy of primary stenting, the rates of both restenosis at 12 months (37 percent) and secondary reintervention at 12 months (29 percent) remain unacceptably high for many patients and payers. There is much opportunity to improve the biologic and mechanical treatments for peripheral-artery disease.
Robert J. Lederman, M.D.
National Heart, Lung, and Blood Institute
Bethesda, MD 20892-1538
lederman@nih.gov
References
de Vries SO, Donaldson MC, Hunink MG. Contralateral symptoms after unilateral intervention for peripheral occlusive disease. J Vasc Surg 1998;27:414-421.
To the Editor: In the accompanying editorial, Hirsch discussed therapeutic choices for patients with peripheral-artery disease. The American College of Cardiology–American Heart Association guidelines1 were developed to improve care and to provide better information for patients.
We were surprised to find that of all the treatment options considered both in the editorial and in the guidelines, there was no mention of one important therapeutic choice: neuromodulation with spinal cord stimulation.
There is evidence to support the use of spinal cord stimulation in patients with inoperable, critical limb ischemia due to peripheral-artery disease. In studies with a follow-up of more than 12 months, this strategy improved limb salvage, reduced ischemic pain, and improved the quality of life.2,3,4We believe that spinal cord stimulation should be one of the therapeutic options offered to patients with peripheral-artery disease.
Pradeep Desai, M.D.
Ranganathan Iyer, M.D.
Wexham Park Hospital
Slough SL2 4HL, United Kingdom
knchndesai@yahoo.co.uk
Srinivas Pyati, M.D.
St. Georges Hospital
Tooting SW17 0QT, United Kingdom
References
Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary: a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Peripheral Arterial Disease). J Am Coll Cardiol 2006;47:1239-1312.
Jivegard LE, Augustinsson LE, Holm J, Risberg B, Ortenwall P. Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study. Eur J Vasc Endovasc Surg 1995;9:421-425.
Amann W, Berg P, Gersbach P, Gamain J, Raphael JH, Ubbink DT. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003;26:280-286.
Ubbink DT, Vermeulen H, Spincemaille GHJJ, Gersbach PA, Berg P, Amann W. Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia. Br J Surg 2004;91:948-955.
The authors reply: With regard to the comments of Dalainas and Nano: we found that in the majority of patients with recurrent in-stent stenosis, repeated balloon angioplasty restores patency and has a very low interventional risk of complications. Assisted patency rates exceed 95 percent if the stent is not totally occluded. In patients with stent occlusions, reinterventions can be complicated by the presence of thrombotic material within the stent. Fortunately, the proportion of reocclusions in our study was small (12 percent in both the stent and angioplasty groups), and frequently reocclusion can still be managed with the use of endovascular strategies. Unfortunately, the study was clearly statistically underpowered (with a beta value of only 5 percent) to demonstrate meaningful differences between groups in the rates of reintervention or surgery. Taking into consideration an annual mortality rate of 5 percent and an annual rate of major cardiac events of 15 percent among patients with symptomatic peripheral-artery disease,1 the goal of endovascular therapy is maximal improvement of the distance walked, mainly for the intermediate term; this goal can be better achieved with the use of primary stenting of long lesions. Different considerations may be involved with respect to the treatment of shorter lesions.
With regard to the comments of Kashyap and colleagues: the proportion of patients taking ACE inhibitors or angiotensin blockers was 65 percent in the stent group and 68 percent in the angioplasty group (P=0.9). We agree that these antihypertensive drugs are the first choice for patients with peripheral-artery disease.
With regard to the comments of Golledge and Norman: the quality of life was measured by the Medical Outcomes Study 36-item Short-Form General Health Survey. These results, together with cost-effectiveness considerations, have yet to be reported. However, given the confounding effects of severe coexisting conditions, we observed considerable variability in the quality of life of our patients during the study. Therefore, the study was underpowered to detect health-related differences in the quality of life; our quality-of-life data are descriptive only and thus were not included in the article. Nevertheless, we agree that improving patients' walking capacity with the use of primary stenting is of definite clinical importance.
With regard to Lederman's comments: as stated above, the study was underpowered to demonstrate or exclude differences in reintervention rates. Ankle pressures were improved nonsignificantly at 6 months and significantly at 12 months. However, readers should be aware that these ankle-pressure measurements were obtained with the patient at rest. Values of the ankle–brachial index after exercise may have shown more pronounced differences, but these measurements are less reproducible and were therefore not performed. With regard to the treadmill walking tests, we did not censor the results with respect to ipsilateral or contralateral invasive procedures; we cannot exclude the possibility that contralateral disease may have influenced the findings. However, the rate of contralateral interventions during the study period was low and similar in each group (4 percent in the stent group and 6 percent in the angioplasty group). Finally, we agree that the restenosis rates in our randomized trial leave room for considerable improvement. However, the reported reduction in the 12-month restenosis rates (on duplex ultrasonography) from 63 percent in the angioplasty group to 37 percent in the stent group is an important advance in the treatment of these patients with long lesions in the superficial femoral artery.
Martin Schillinger, M.D.
Erich Minar, M.D.
Medical University of Vienna
A-1090 Vienna, Austria
martin.schillinger@meduniwien.ac.at
References
Schillinger M, Exner M, Amighi J, et al. Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis. Circulation 2003;108:2323-2328.
The editorialist replies: It is increasingly recognized internationally that the clinical investigation of potential new therapies for peripheral-artery disease will require more contemplative approaches. As noted, if it is to be realized, the promise of "therapeutic choice" will require trials of new therapies in larger populations, with better use of relevant subjective end points.
Desai and colleagues remind readers that — beyond nitinol stents — other devices offer promise to improve the outcomes of peripheral-artery disease. Spinal cord stimulation has been shown to improve both ischemic pain and microcirculatory perfusion in the limb. Although current data suggest that spinal cord stimulation can increase blood flow to the skin and improve limb salvage in patients with critical limb ischemia, this database is generally limited in scope.1,2 The statistical "signal" of potential limb salvage appears more evident in meta-analyses than in individual trials, and the current database does not yet fully inform us with regard to key benefits or risks. Yet many patients with refractory symptoms of critical limb ischemia might choose spinal cord stimulation if the data were more robust.
Golledge and Norman correctly cite the important role of quality-of-life instruments in research on peripheral-artery disease. Over the past decade, numerous instruments specific to peripheral-artery disease have been validated for use as clinical research tools.3,4 The measurements obtained with the use of these tools have not traditionally served as the primary outcome for claudication trials, but they could become a primary-outcome standard in the future. Arterial patency, the most common outcome assessment in revascularization trials, provides but one potential mechanism that could underlie putative clinical benefit. The lower limb is a complex end organ, and patency alone is not a reliable surrogate for the health-related quality of life among patients with peripheral-artery disease. Only quality-of-life data inform clinicians and patients of the real value of intervention for peripheral-artery disease.
Desai and colleagues and Golledge and Norman have also, in their letters, reminded readers that the enterprise of clinical research on peripheral-artery disease is inherently international. Peripheral-artery disease is pandemic, and the preservation of functional independence is a universal value. So, too, the investigational effort of peripheral-artery disease is global. Future clinical investigations of the disease will increasingly require a scale that more appropriately reflects the international disease burden. The assessment of currently promising interventions in peripheral-artery disease (and therapies not yet imagined) will require an investment of resources and international, collaborative goodwill.
Alan T. Hirsch, M.D.
University of Minnesota School of Public Health
Minneapolis, MN 55455
References
Amann W, Berg P, Gersbach P, Gamain J, Raphael JH, Ubbink DT. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003;26:280-286.
Ubbink DT, Vermeulen H, Spincemaille GHJJ, Gersbach PA, Berg P, Amann W. Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia. Br J Surg 2004;91:948-955.
Spertus J, Jones P, Poler S, Rocha-Singh K. The Peripheral Artery Questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease. Am Heart J 2004;147:301-308.
Chong PF, Garratt AM, Golledge J, Greenhalgh RM, Davies AH. The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure. J Vasc Surg 2002;36:764-771.
Ilias Dalainas, M.D., Ph.D.
Giovanni Nano, M.D.
University of Milan
20097 Milan, Italy
hdlns@freemail.gr
References
Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med 2006;354:1879-1888.
To the Editor: Schillinger et al. compared balloon angioplasty with the implantation of nitinol stents in the superficial femoral artery. The authors provided no information about the specific antihypertensive medications being taken by the study patients, particularly the number of patients who were taking angiotensin-converting–enzyme (ACE) inhibitors in each group. In a randomized trial, Ahimastos et al. demonstrated that treatment with an ACE inhibitor (ramipril) for 24 weeks increased the pain-free walking time and the maximum walking time in a clinically and statistically significant manner, as compared with current therapies in peripheral-artery disease.1 ACE inhibitors improve the flow of blood to the lower extremities in patients with peripheral-artery disease. The mechanisms include reduced levels of angiotensin II, improved endothelial function, sympathetic inhibition, angiogenesis (collateral formation), and regression of atherosclerosis.1
Ajit Kashyap, M.D.
Command Hospital (Central Command)
Lucknow 226 002, India
kashyapajits@yahoo.com
Kuldip Parkash Anand, M.D.
Command Hospital (Eastern Command)
Kolkata 700 027, India
Surekha Kashyap, M.D.
Command Headquarters (Central Command)
Lucknow 226 002, India
References
Ahimastos AA, Lawfer A, Reid CM, Blombery PA, Kingwell BA. Ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med 2006;144:660-664.
To the Editor: As outlined in the accompanying editorial by Hirsch, well-conducted trials that examine interventions for peripheral-artery disease are needed.1 Since the risk of limb loss is low during the long-term follow-up of patients with intermittent claudication, the primary objective of interventions is to improve the health-related quality of life.2 Although objective measures such as patency on imaging, ankle pressures, and the distance walked on treadmills provide important information about the results of interventions, they do not assess the patients' quality of life.3 A number of tools have been developed specifically to measure the quality of life in patients presenting with intermittent claudication.2,3,4 In this regard, it is disappointing that none of these measures were used by Schillinger and colleagues. Since we have no evidence to suggest that improved patency of lower-limb arteries has any definite benefit, it is important that we investigate the value of treatments for intermittent claudication in terms of the quality of life.
Jonathan Golledge, M.Chir.
James Cook University
Townsville, QLD 4811, Australia
jonathan.golledge@jcu.edu.au
Paul Norman, D.S.
University of Western Australia
Perth, WA 6959, Australia
References
Hirsch AT. Treatment of peripheral arterial disease -- extending "intervention" to "therapeutic choice." N Engl J Med 2006;354:1944-1947.
Golledge J, Askew C, Leicht A, Oldenburg B. Outcome assessment for intermittent claudication. Eur J Vasc Endovasc Surg 2006;31:44-45.
Mehta T, Venkata Subramaniam A, Chetter I, McCollum P. Assessing the validity and responsiveness of disease-specific quality of life instruments in intermittent claudication. Eur J Vasc Endovasc Surg 2006;31:46-52.
Chong PF, Garratt AM, Golledge J, Greenhalgh RM, Davies AH. The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure. J Vasc Surg 2002;36:764-771.
To the Editor: In the important study by Schillinger et al., it is curious that the rates of repeated intervention were similar in both the primary-stenting and provisional-stenting groups. It is also curious that the functional and anatomical end points were so discordant: the rate of angiographic restenosis and the distance walked on a treadmill were both improved dramatically in the stent group as compared with the angioplasty group, but ankle pressures and the rate of reocclusion were not significantly influenced by stenting.
One challenge in the analysis of studies of lower-extremity interventions is that patients generally have two legs. Contralateral, even symmetric, patterns of obstructive atherosclerosis are common, as are contralateral symptoms and treatments.1 Could the authors comment on the interaction of contralateral disease and interventions on the study end points, as well as how the treadmill data were reported or censored in relation to subsequent ipsilateral and contralateral invasive procedures?
Finally, even with the use of the strategy of primary stenting, the rates of both restenosis at 12 months (37 percent) and secondary reintervention at 12 months (29 percent) remain unacceptably high for many patients and payers. There is much opportunity to improve the biologic and mechanical treatments for peripheral-artery disease.
Robert J. Lederman, M.D.
National Heart, Lung, and Blood Institute
Bethesda, MD 20892-1538
lederman@nih.gov
References
de Vries SO, Donaldson MC, Hunink MG. Contralateral symptoms after unilateral intervention for peripheral occlusive disease. J Vasc Surg 1998;27:414-421.
To the Editor: In the accompanying editorial, Hirsch discussed therapeutic choices for patients with peripheral-artery disease. The American College of Cardiology–American Heart Association guidelines1 were developed to improve care and to provide better information for patients.
We were surprised to find that of all the treatment options considered both in the editorial and in the guidelines, there was no mention of one important therapeutic choice: neuromodulation with spinal cord stimulation.
There is evidence to support the use of spinal cord stimulation in patients with inoperable, critical limb ischemia due to peripheral-artery disease. In studies with a follow-up of more than 12 months, this strategy improved limb salvage, reduced ischemic pain, and improved the quality of life.2,3,4We believe that spinal cord stimulation should be one of the therapeutic options offered to patients with peripheral-artery disease.
Pradeep Desai, M.D.
Ranganathan Iyer, M.D.
Wexham Park Hospital
Slough SL2 4HL, United Kingdom
knchndesai@yahoo.co.uk
Srinivas Pyati, M.D.
St. Georges Hospital
Tooting SW17 0QT, United Kingdom
References
Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary: a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Peripheral Arterial Disease). J Am Coll Cardiol 2006;47:1239-1312.
Jivegard LE, Augustinsson LE, Holm J, Risberg B, Ortenwall P. Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study. Eur J Vasc Endovasc Surg 1995;9:421-425.
Amann W, Berg P, Gersbach P, Gamain J, Raphael JH, Ubbink DT. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003;26:280-286.
Ubbink DT, Vermeulen H, Spincemaille GHJJ, Gersbach PA, Berg P, Amann W. Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia. Br J Surg 2004;91:948-955.
The authors reply: With regard to the comments of Dalainas and Nano: we found that in the majority of patients with recurrent in-stent stenosis, repeated balloon angioplasty restores patency and has a very low interventional risk of complications. Assisted patency rates exceed 95 percent if the stent is not totally occluded. In patients with stent occlusions, reinterventions can be complicated by the presence of thrombotic material within the stent. Fortunately, the proportion of reocclusions in our study was small (12 percent in both the stent and angioplasty groups), and frequently reocclusion can still be managed with the use of endovascular strategies. Unfortunately, the study was clearly statistically underpowered (with a beta value of only 5 percent) to demonstrate meaningful differences between groups in the rates of reintervention or surgery. Taking into consideration an annual mortality rate of 5 percent and an annual rate of major cardiac events of 15 percent among patients with symptomatic peripheral-artery disease,1 the goal of endovascular therapy is maximal improvement of the distance walked, mainly for the intermediate term; this goal can be better achieved with the use of primary stenting of long lesions. Different considerations may be involved with respect to the treatment of shorter lesions.
With regard to the comments of Kashyap and colleagues: the proportion of patients taking ACE inhibitors or angiotensin blockers was 65 percent in the stent group and 68 percent in the angioplasty group (P=0.9). We agree that these antihypertensive drugs are the first choice for patients with peripheral-artery disease.
With regard to the comments of Golledge and Norman: the quality of life was measured by the Medical Outcomes Study 36-item Short-Form General Health Survey. These results, together with cost-effectiveness considerations, have yet to be reported. However, given the confounding effects of severe coexisting conditions, we observed considerable variability in the quality of life of our patients during the study. Therefore, the study was underpowered to detect health-related differences in the quality of life; our quality-of-life data are descriptive only and thus were not included in the article. Nevertheless, we agree that improving patients' walking capacity with the use of primary stenting is of definite clinical importance.
With regard to Lederman's comments: as stated above, the study was underpowered to demonstrate or exclude differences in reintervention rates. Ankle pressures were improved nonsignificantly at 6 months and significantly at 12 months. However, readers should be aware that these ankle-pressure measurements were obtained with the patient at rest. Values of the ankle–brachial index after exercise may have shown more pronounced differences, but these measurements are less reproducible and were therefore not performed. With regard to the treadmill walking tests, we did not censor the results with respect to ipsilateral or contralateral invasive procedures; we cannot exclude the possibility that contralateral disease may have influenced the findings. However, the rate of contralateral interventions during the study period was low and similar in each group (4 percent in the stent group and 6 percent in the angioplasty group). Finally, we agree that the restenosis rates in our randomized trial leave room for considerable improvement. However, the reported reduction in the 12-month restenosis rates (on duplex ultrasonography) from 63 percent in the angioplasty group to 37 percent in the stent group is an important advance in the treatment of these patients with long lesions in the superficial femoral artery.
Martin Schillinger, M.D.
Erich Minar, M.D.
Medical University of Vienna
A-1090 Vienna, Austria
martin.schillinger@meduniwien.ac.at
References
Schillinger M, Exner M, Amighi J, et al. Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis. Circulation 2003;108:2323-2328.
The editorialist replies: It is increasingly recognized internationally that the clinical investigation of potential new therapies for peripheral-artery disease will require more contemplative approaches. As noted, if it is to be realized, the promise of "therapeutic choice" will require trials of new therapies in larger populations, with better use of relevant subjective end points.
Desai and colleagues remind readers that — beyond nitinol stents — other devices offer promise to improve the outcomes of peripheral-artery disease. Spinal cord stimulation has been shown to improve both ischemic pain and microcirculatory perfusion in the limb. Although current data suggest that spinal cord stimulation can increase blood flow to the skin and improve limb salvage in patients with critical limb ischemia, this database is generally limited in scope.1,2 The statistical "signal" of potential limb salvage appears more evident in meta-analyses than in individual trials, and the current database does not yet fully inform us with regard to key benefits or risks. Yet many patients with refractory symptoms of critical limb ischemia might choose spinal cord stimulation if the data were more robust.
Golledge and Norman correctly cite the important role of quality-of-life instruments in research on peripheral-artery disease. Over the past decade, numerous instruments specific to peripheral-artery disease have been validated for use as clinical research tools.3,4 The measurements obtained with the use of these tools have not traditionally served as the primary outcome for claudication trials, but they could become a primary-outcome standard in the future. Arterial patency, the most common outcome assessment in revascularization trials, provides but one potential mechanism that could underlie putative clinical benefit. The lower limb is a complex end organ, and patency alone is not a reliable surrogate for the health-related quality of life among patients with peripheral-artery disease. Only quality-of-life data inform clinicians and patients of the real value of intervention for peripheral-artery disease.
Desai and colleagues and Golledge and Norman have also, in their letters, reminded readers that the enterprise of clinical research on peripheral-artery disease is inherently international. Peripheral-artery disease is pandemic, and the preservation of functional independence is a universal value. So, too, the investigational effort of peripheral-artery disease is global. Future clinical investigations of the disease will increasingly require a scale that more appropriately reflects the international disease burden. The assessment of currently promising interventions in peripheral-artery disease (and therapies not yet imagined) will require an investment of resources and international, collaborative goodwill.
Alan T. Hirsch, M.D.
University of Minnesota School of Public Health
Minneapolis, MN 55455
References
Amann W, Berg P, Gersbach P, Gamain J, Raphael JH, Ubbink DT. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS). Eur J Vasc Endovasc Surg 2003;26:280-286.
Ubbink DT, Vermeulen H, Spincemaille GHJJ, Gersbach PA, Berg P, Amann W. Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia. Br J Surg 2004;91:948-955.
Spertus J, Jones P, Poler S, Rocha-Singh K. The Peripheral Artery Questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease. Am Heart J 2004;147:301-308.
Chong PF, Garratt AM, Golledge J, Greenhalgh RM, Davies AH. The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure. J Vasc Surg 2002;36:764-771.