Wouldn’t it be great if medicine could borrow from the science behind percutaneous coronary arterial stenting (used over 600,000 times per year in the United States for coronary ischemia) in order to treat a chronic and widespread disease such as hypertension? The CORAL trial (Cardiovascular Outcomes in Renal Atherosclerotic Lesions), published in this week’s NEJM, examines this exact question.
Over 77 million people in the United States have hypertension. Renal-artery stenosis is present in 1-5% of those with hypertension, and is thought to play a significant causative role in the development of hypertension. As such, treatment of renal artery stenosis has been the focus of clinical investigations since the 1990s. Uncontrolled studies from this time, including one published in NEJM suggested renal artery stenting provided clinical benefits in the treatment of hypertension and chronic kidney disease. By the year 2000, an estimated twenty-one thousand renal revascularization procedures were performed in the United States annually.
Despite the now frequent use of renal artery stenting, more recent randomized control trials have not been able to reproduce the positive results published two decades ago. The ASTRAL trial (Revascularization versus Medical Therapy for Renal-Artery Stenosis), published in NEJM in 2009 found no significant benefit of renal stenting plus medical therapy over medical therapy alone with respect to renal function. However, critics of ASTRAL have focused on to its inclusion of non-clinically relevant renal artery stenosis and absence of clinically relevant endpoints.
CORAL aimed to address these prior concerns. A multicenter, open-label, randomized control trial, it compared medical therapy alone versus medical therapy plus renal artery stenting in patients with (1) atherosclerotic renal artery stenosis and (2) hypertension and/or chronic kidney disease. In response to the critiques described above, CORAL’s authors limited inclusion criteria to patients with atherosclerotic renal artery stenosis greater than or equal to 60%. Additionally, they defined their primary outcome as a composite of major cardiac (acute coronary syndrome, admission for acute congestive heart failure) and renal (initiation of renal replacement therapy or greater than 30% decrease in the patient’s baseline GFR lasting for greater than 60 days) events.
About 450 patients were randomly assigned to receive medical therapy alone or medical therapy plus renal artery stenting. Patients were followed for a median of just under 4 years. In the intention-to-treat analysis, there was no significant difference between the two groups with respect to the primary endpoint (169 patients in the medical therapy group, 161 patients in the medical therapy plus stenting group, p = .58).
In the associated editorial, Dr. John A Bittl, interventional cardiologist and prior critic of renal artery stenting, states that CORAL “establishes beyond a reasonable doubt that renal-artery stenting is futile for the target population enrolled in the study”. Moreover, he believes that CORAL supports a more aggressive pharmacologic approach for patients with hypertension, chronic kidney disease and renal artery stenosis.
One sobering reminder from CORAL was the significant rate of harm caused by renal artery stenting: of the 495 renal artery stents that were placed, 11 (2.2%) were complicated by arterial dissection, 6 by branch vessel occlusion, and 6 by angiographically evident distal embolization. The ASTRAL trial raised similar concern for iatrogenic harm in renal stenting.
In conclusion, CORAL provides strong evidence that renal artery stenting provides no significant benefit to patients with moderately severe atherosclerotic renovascular disease, and may actually pose an unnecessary risk. Unless future studies are able to demonstrate a benefit of stenting in populations with even more severe renovascular disease, the technology behind coronary stenting may have little to offer those interested in preventing complications of hypertension and renal artery stenosis.