Relationship of Albuminuria and Renal Artery Stent Outcomes: Results From the CORAL Randomized Clinical Trial (Cardiovascular Outcomes With Renal Artery Lesions)

Abstract

Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease- or kidney disease-related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P=0.02), cardiovascular disease-related death (93% versus 85%; P≤ 0.01), progressive renal insufficiency (91% versus 77%; P=0.03), and overall survival (89% versus 76%; P≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00081731.

Keywords: arteriosclerosis; myocardial infarction; renal artery obstruction; renal insufficiency; stents; stroke.

Conflict of interest statement

Conflict of Interest Disclosures: Timothy P, Murphy: Current Employer: Rhode Island Medical Imaging, Inc.; Ownership Interest: Sentient Bioscience, Summa Therapeutics, Saphena Medical, Anaxiom, Inc.; Research Funding: Cordis/Johnson & Johnson; Abbott Vascular; National Institutes of Health; Novate Medical; The Medicines Company; National Heart Lung and Blood Institute; Honoraria: Merit Medical. Christopher J. Cooper: Current Employer: University of Toledo; Research Funding: Pfizer, AstraZeneca, Cordis, National Heart Lung and Blood Institute. Karol M. Pencina: Disclosure Information: nothing to disclose. Ralph B. D’Agostino: Current Employer: Boston University; Consultancy Agreements: Harvard Clinical Research Institute (consultant), Progeria Foundation (consultant); Scientific Advisor or Membership: Statistics in Medicine (editor), New England Journal of Medicine (editorial board). Joseph Massaro: Current Employer: Boston University School of Public Health, Harvard Clinical Research Institute; Disclosure Information: nothing to disclose. Donald Cutlip: Current Employer: Beth Israel Deaconess Medical Center; Research Funding: Medtronic. Kenneth A. Jamerson: Current Employer: University of Michigan Health System; Research Funding: National Institutes of Health; Scientific Advisor or Membership: National Institutes of Health. Alan Matsumoto: Current Employer: University of Virginia; Ownership Interest: Volcano; Research Funding: W.L. Gore, Medtronic, Insightec, Cook; Honoraria: Trivascular, Bolton Medical, W.L. Gore; Scientific Advisor or Membership: Boston Scientific, Tenex Medical, BrightWater. William L. Henrich: Current Employer: University of Texas-San Antonio; Disclosure Information: nothing to disclose. Joseph I. Shapiro: Current Employer: Marshall University; Ownership Interest: ADS Biotechnology. Honoraria: West Virginia University; University of Colorado; Ohio State University; Cleveland Clinic Foundation; Wayne State University; Henry Ford Hospital; Medical University of South Carolina; University of Toledo; University of Pisa; University of Catania. Scientific Advisor or Membership: ADS Biotechnology Board of Directors (Chairman); Alliance for Paired Donation Board of Directors; American Heart Association (Ohio Valley Affiliate) Board of Directors; Promedica Health Systems Academic Health Center Board of Directors; Regional Growth Partnership of NW Ohio Scientific Advisory Board; Editorial Board Member for Kidney Int, Frontiers Biosci. Biol Res Nurs, Am J Medicine, Am. Soc. Art Intern Org, Hypertension, Int J Hypertens, J Signal Trans, World J Hypertens. Katherine R. Tuttle: Current Employer: Providence Health Care, University of Washington School of Medicine; Consultancy Agreements: Eli Lilly, Amgen, Noxxon Pharma; Honoraria: Primary Care Update, American Diabetes Association, National Kidney Foundation, Spokane Society of Internal Medicine, University of Colorado, Quintiles, Duke University, University of North Carolina, Cleveland Clinic; Scientific Advisor or Membership: CJASN, Am J Nephrol, NIDDK/NKDEP, Kidney Health Initiative, US Veteran’s Administration. David J. Cohen: Current Employer: St. Luke’s Hospital-Kansas City; Disclosure Information: Research Funding: Medtronic, Boston Scientific, Abbott Vascular; Consultancy Agreements: Medtronic, Abbott Vascular; Michael Steffes: Current Employer: University of Minnesota; Disclosure Information: nothing to disclose. Qi Gao: Current Employer: Harvard Clinical Research Institute; Disclosure Information: nothing to disclose. Christopher Metzger: Current Employer: Wellmont-Holston Valley Medical Center; Consultancy Agreements: Abbott, TriVascular; Honoraria: Abbott, Boston Scientific, Bard. William Abernethy: Current Employer: Asheville Cardiology Associates; Disclosure Information: nothing to disclose. Stephen C. Textor: Current Employer: Mayo Clinic; Research Funding: Stealth Peptides, Inc. John Briguglio: Current Employer: Lancaster General Hospital; Disclosure Information: nothing to disclose. Alan Hirsch: Current Employer: University of Minnesota; Consultancy Agreements: Merck, Novartis, Bayer; Research Funding: AstraZeneca, National Heart Lung and Blood Institute, Pluristem; Other Interest/Relationships: Tactile Medical: Chief Medical Officer. Sheldon W. Tobe: Consultancy Agreements: AbbVie Inc.; Research Funding: Astra Zeneca, Pfizer, Bayer; Scientific Advisor or Membership: American Society of Hypertension. Lance D. Dworkin: Current Employer: University Medicine Foundation; Research Funding: Astra Zeneca, National Institutes of Health, Cordis/Johnson & Johnson; Scientific Advisor or Membership: Clinical Journal of the American Society of Nephrology editorial board.

© 2016 American Heart Association, Inc.

Figures

Figure 1

Freedom from the primary composite endpoint* through 5 years of follow-up by treatment group and uACR cohort. For baseline uACR median, the 5-year freedom from event for Stent vs. Medical groups was 47% vs. 48%, p=.38 (log-rank test). *Primary composite endpoint = myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, (>=30% reduction in estimated glomerular filtration rate (eGFR) sustained at least 60 days), or cardiovascular- or kidney disease-related death.

Figure 2

Forest plot displaying treatment effects within uACR decile sub-groups.

Figure 3

Systolic Blood Pressure Treatment Effects. Systolic blood pressure (group mean ± 1 SE) over time. Difference not significant for Cohort 1 (n=413, p=.58). Test for interaction of group*visit P-value is 0.68. There is a trend favoring stent in Cohort 2 (n=413, p=.052). Test for interaction of group*visit P-value is 0.45. Cohort 1=baseline uACR22.5 mg/g.