Author's Accepted Manuscript
Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies Matthew A. Corriere MD, Matthew S. Edwards MD
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S0895-7967(14)00021-0 http://dx.doi.org/10.1053/j.semvascsurg.2014.06.003 YSVAS50428
To appear in: ĆSemin Vasc Surg
Cite this article as: Matthew A. Corriere MD, Matthew S. Edwards MD, Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies, ĆSemin Vasc Surg , http://dx.doi. org/10.1053/j.semvascsurg.2014.06.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies
Matthew A. Corriere MD and Matthew S. Edwards MD Department of Vascular and Endovascular Surgery Wake Forest University Baptist Medical Center Winston‐Salem, North Carolina Correspondence:
Matthew S. Edwards MD
Department of Vascular and Endovascular Surgery
Wake Forest University Baptist Medical Center
Winston‐Salem, NC 27157
Email: [email protected]
Phone: (336) 716‐9502
Introduction The surgical care of patients with renal artery stenosis has been a topic of controversy for many years. The gold standard for treatment in the latter part of the 20th century consisted of renal artery bypass or endarterectomy. In highly selected patients with revascularization performed by skilled surgeons at high volume centers, significant blood pressure and renal function responses were observed in approximately 85% and 50% of patients, respectively1‐3. In‐hospital mortality rates ranged from 2‐5% and substantial morbidity was common1‐3. In the latter years of the 20th century, endovascular treatment of renal artery stenosis with angioplasty and stenting became the most common method of renal revascularization, demonstrating much lower rates of morbidity and mortality but also lower rates
of blood pressure and renal function improvement4. To date, no definitive comparative data exist that demonstrate the relative utility of open surgical revascularization versus endovascular renal revascularization or best medical management. Three recent randomized clinical trials compared endovascular renal revascularization versus best medical management: The benefit of STent placement and blood pressure and lipid‐lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery (STAR) trial5, the Angioplasty and STenting for Renal Artery Lesions (ASTRAL) trial6, and the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial7. This review will summarize the design, inclusion and exclusion criteria, conduct, and results of the two larger trials (ASTRAL and CORAL) and consider their implications for future treatment strategies for atherosclerotic renovascular disease. Results of the Major Clinical Trials The ASTRAL Trial The ASTRAL trial6 which was performed with the goal of determining whether stenting of the renal artery (RA‐PTAS) combined with best medical therapy improved renal function and other outcomes when compared with best medical therapy alone. ASTRAL was a prospective, randomized, unblinded clinical trial that enrolled patients with uncontrolled or refractory hypertension and/or renal dysfunction that were presumed to be secondary to RAS. Hemodynamically significant RAS was anatomically angiography, CT angiography, MR angiography, or duplex. Importantly, physician uncertainty regarding the expected benefit from RA‐PTAS was a criterion for trial participation, resulting in exclusion of individuals considered by their physician to have the greatest potential for procedure‐related benefit. Individuals requiring surgical reconstruction and those with prior renal artery revascularization were excluded.
The primary outcome of ASTRAL was change in the reciprocal of serum creatinine, with enrollment targeted for a power to detect a 20% decrease in the expected decline (0.0016 l/micromole/year) in the medical treatment group. Secondary outcomes included blood pressure response, renal and cardiovascular disease event‐free survival, and mortality. Eight hundred six patients were randomized with an even distribution to each treatment arm achieved. Seventeen percent of the stent group did not have a stent procedure for a variety of reasons, and 6% of people randomized to the medical treatment group crossed over and were treated with angioplasty and stenting. Participants were similar in terms of baseline demographics, co morbidities, blood pressure, and renal function, and the rate of loss to follow up was
Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies Matthew A. Corriere MD, Matthew S. Edwards MD
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S0895-7967(14)00021-0 http://dx.doi.org/10.1053/j.semvascsurg.2014.06.003 YSVAS50428
To appear in: ĆSemin Vasc Surg
Cite this article as: Matthew A. Corriere MD, Matthew S. Edwards MD, Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies, ĆSemin Vasc Surg , http://dx.doi. org/10.1053/j.semvascsurg.2014.06.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Results of the major randomized clinical trials of renal stenting and implications for future treatment strategies
Matthew A. Corriere MD and Matthew S. Edwards MD Department of Vascular and Endovascular Surgery Wake Forest University Baptist Medical Center Winston‐Salem, North Carolina Correspondence:
Matthew S. Edwards MD
Department of Vascular and Endovascular Surgery
Wake Forest University Baptist Medical Center
Winston‐Salem, NC 27157
Email: [email protected]
Phone: (336) 716‐9502
Introduction The surgical care of patients with renal artery stenosis has been a topic of controversy for many years. The gold standard for treatment in the latter part of the 20th century consisted of renal artery bypass or endarterectomy. In highly selected patients with revascularization performed by skilled surgeons at high volume centers, significant blood pressure and renal function responses were observed in approximately 85% and 50% of patients, respectively1‐3. In‐hospital mortality rates ranged from 2‐5% and substantial morbidity was common1‐3. In the latter years of the 20th century, endovascular treatment of renal artery stenosis with angioplasty and stenting became the most common method of renal revascularization, demonstrating much lower rates of morbidity and mortality but also lower rates
of blood pressure and renal function improvement4. To date, no definitive comparative data exist that demonstrate the relative utility of open surgical revascularization versus endovascular renal revascularization or best medical management. Three recent randomized clinical trials compared endovascular renal revascularization versus best medical management: The benefit of STent placement and blood pressure and lipid‐lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery (STAR) trial5, the Angioplasty and STenting for Renal Artery Lesions (ASTRAL) trial6, and the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial7. This review will summarize the design, inclusion and exclusion criteria, conduct, and results of the two larger trials (ASTRAL and CORAL) and consider their implications for future treatment strategies for atherosclerotic renovascular disease. Results of the Major Clinical Trials The ASTRAL Trial The ASTRAL trial6 which was performed with the goal of determining whether stenting of the renal artery (RA‐PTAS) combined with best medical therapy improved renal function and other outcomes when compared with best medical therapy alone. ASTRAL was a prospective, randomized, unblinded clinical trial that enrolled patients with uncontrolled or refractory hypertension and/or renal dysfunction that were presumed to be secondary to RAS. Hemodynamically significant RAS was anatomically angiography, CT angiography, MR angiography, or duplex. Importantly, physician uncertainty regarding the expected benefit from RA‐PTAS was a criterion for trial participation, resulting in exclusion of individuals considered by their physician to have the greatest potential for procedure‐related benefit. Individuals requiring surgical reconstruction and those with prior renal artery revascularization were excluded.
The primary outcome of ASTRAL was change in the reciprocal of serum creatinine, with enrollment targeted for a power to detect a 20% decrease in the expected decline (0.0016 l/micromole/year) in the medical treatment group. Secondary outcomes included blood pressure response, renal and cardiovascular disease event‐free survival, and mortality. Eight hundred six patients were randomized with an even distribution to each treatment arm achieved. Seventeen percent of the stent group did not have a stent procedure for a variety of reasons, and 6% of people randomized to the medical treatment group crossed over and were treated with angioplasty and stenting. Participants were similar in terms of baseline demographics, co morbidities, blood pressure, and renal function, and the rate of loss to follow up was
