When the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study determined that renal revascularization really did not benefit most elderly patients with renal artery stenosis (N Engl J Med 2014;370:13-22), the sparks began to fly in the medical community.
CORAL study chair Lance D. Dworkin, MD, Brown Medical School’s vice chairman of Medicine for Research, Academic Affairs and Ethics, and Director of the Division of Kidney Disease & Hypertension, discusses the controversial finding with Renal & Urology News.
What were your duties as CORAL chair?
Dr. Dworkin: As study chair, I was responsible for the overall design and conduct of the trial. I was involved in virtually every aspect of the study, including design, redesign, and modifications; tracking and responding to issues with enrolled people including recruitment, retention, safety, data collection, and data analysis; writing of papers; approval of ancillary studies; and on and on. I chaired the weekly meetings of the operations committee, which dealt with day-to-day issues in completing the study.
I led the investigators’ presentations and responses to the National Institutes of Health and the Data Safety and Monitoring Committee. I interacted with sponsors, site investigators, staff, and anyone else related to the study. I made multiple presentations about the study and made site visits to enrolling centers to encourage enrollment, retention, and adherence to the protocol. I chaired our investigators’ meetings. When there were disagreements about the trial among the investigators, it was my job to make sure we found the common ground.
It was a great responsibility and a great privilege to chair the study. I relied heavily on our outstanding investigative team, particularly the operations committee (Chris Cooper, Tim Murphy, Bill Henrich, Don Cutlip, and Ken Jamerson), and the chairs of our subcommittees and core labs (Alan Matsumoto, Michael Jaff, Mike Steffes, Martin Prince, David Cohen, Kathy Tuttle, Joe Shapiro, and John Rundback).
The CORAL study showed that renal stenting was no more beneficial than medical management in preventing major adverse renal and cardiovascular events in elderly persons with atherosclerotic renal artery stenosis.
Why was this outcome so noteworthy?
Dr. Dworkin: There has been an ongoing debate for many years as to whether renal revascularization, currently most commonly performed by angioplasty and stenting, improved outcomes for patients with atherosclerotic renal artery stenosis.
In many centers, renal revascularization is commonly performed on such patients; in other centers it is rarely done. The usual justifications given for performing renal artery interventions are:
- to better control blood pressure in people with resistant hypertension
- to preserve kidney function and delay progression to end-stage renal disease
- to prevent recurrent episodes of severe congestive heart failure
In fact, despite at least 6 prior randomized clinical trials, there was no convincing evidence that stenting improved any of these outcomes, or prevented adverse cardiovascular events in these patients. Nevertheless, some patients appear to benefit, and the prior trials were all considered to be seriously flawed in critical ways.
CORAL was the first and most carefully designed trial to compare the effects of stenting to an optimal medical regimen on clinical outcomes in patients with renal artery stenosis.
The fact that it also showed no benefit of stenting on average will hopefully convince practitioners, finally, that renal artery interventions should only be performed, if at all, on patients who have really failed medical therapy, and not on stable patients with renal artery lesions.
Who is disputing these findings, and why?
Dr. Dworkin: Some practitioners, primarily interventionalists (who may be cardiologists) interventional radiologists, or vascular surgeons, may still not be fully convinced that renal revascularization is of no benefit to the majority of patients.
In conducting any clinical trial, compromises are made in order to design and complete the study in a reasonable amount of time. This is true of CORAL. As a result, some practitioners may continue to believe that stent revascularization is the best treatment for some patients.
In fact, CORAL does not show that revascularization fails to help all patients. Some might still benefit from an intervention. What CORAL shows is that on average, for patients with atherosclerotic renal artery stenosis that had previously often been treated with stents, outcomes are equally good for patients who are treated medically without stents.
What is the standard medical management for renal artery stenosis?
Dr. Dworkin: There have been no randomized clinical trials examining the best medical therapy for patients with renal artery stenosis. The medical regimen used in CORAL was developed from standard clinical practice guidelines and from studies in other populations with hypertension.
It included treatment of blood pressure to the recommended goals of 140/90 mm Hg in uncomplicated patients and to 130/80 in patients with diabetes or chronic kidney disease, using a combination of drugs that are all approved and available in generic form. It included an angiotensin receptor antagonist with or without a thiazide diuretic and a dihydropyridine calcium channel blocker.
Patients also received a statin titrated to achieve the recommended LDL cholesterol less than 70 mg/dL, and some form of antiplatelet therapy, at least daily aspirin. Patients with diabetes were treated by any clinically approved method to a target HbA1c less than 7. Patients with chronic kidney disease had anemia, calcium, phosphate and vitamin D administered according to the KDIGO [Kidney Disease Improving Global Outcomes; www.kdigo.org] clinical practice guidelines.
Patients who smoked were encouraged to stop or entered into formal smoking-cessation programs. This approach resulted in a lower than expected rate of cardiovascular and renal adverse events.