Alternative Interpretation of ASTRAL and CORAL Suggests a Role for Renal Artery Intervention

April 8, 2015—In the European Journal of Vascular and Endovascular Surgery (EJVES), Irwin V. Mohan, MD, et al published an assessment of the literature on intervention for renal artery stenosis (RAS), with special emphasis on the frequently debated ASTRAL and CORAL randomized trials (2015;49:465–473). The investigators provide an alternative interpretation of the data in the ASTRAL and CORAL trials, which had concluded that no benefit was associated with RAS.

The assessment published in EJVES was designed to review renal physiology, pathology, and pathophysiology of RAS, and provide a critical analysis of the randomized trials. Particular attention was devoted to an analysis of these factors and the limitations and challenges encountered in both ASTRAL and CORAL, which are the most recently reported and the largest randomized trials of percutaneous renal artery intervention.

The investigators point out that the two trials generated much debate and much controversy, and both had methodological shortcomings and assumed a simplistic approach to renal physiology. ASTRAL was published in The New England Journal of Medicine (2009;361:1953–1962). CORAL was published in The New England Journal of Medicine (2014;370:13–22). 

Among the issues highlighted in the current publication are that both ASTRAL and CORAL were hampered by slow recruitment, and there were protocol changes to accommodate. Additionally, CORAL was determined to not have been powered for subgroup analysis. The primary outcome measure for ASTRAL was the reciprocal of serum creatinine levels, while in CORAL, it was a complex composite endpoint of cardiovascular or renal events. 

In ASTRAL, 25% of patients had normal renal function, and 40% had almost-normal renal function; in CORAL, 50% of the cohort had either no renal failure, or were Stage I or Stage II chronic kidney disease. In ASTRAL, 41% of patients had a RAS < 70%; an interim analysis of 611 patients (of 947 enrolled) in CORAL revealed that 55% had RAS < 70%.

The CORAL investigators concluded, “Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic RAS and hypertension or chronic kidney disease.” The ASTRAL investigators concluded, “We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.” 

However, the assessment in EJVES concluded that the best evidence still supports intervention for patients with RAS of > 80% with a significant translesional pressure gradient; difficult-to-control blood pressure with more than three antihypertensives, especially in younger patients; truncal rather than ostial stenosis; rapid deterioration of renal function; flash pulmonary edema; and post-transplant RAS.