Stenting and medical therapy for atherosclerotic renal-artery stenosis (CHORAL)
Selected in The New England Journal of Medicine by G. Harris
Christopher J. Cooper, M.D., Timothy P. Murphy, M.D., Donald E. Cutlip, M.D., Kenneth Jamerson, M.D., William Henrich, M.D., Diane M. Reid, M.D., David J. Cohen, M.D., Alan H. Matsumoto, M.D., Michael Steffes, M.D., Michael R. Jaff, D.O., Martin R. Prince, M.D., Ph.D., Eldrin F. Lewis, M.D., Katherine R. Tuttle, M.D., Joseph I. Shapiro, M.D., M.P.H., John H. Rundback, M.D., Joseph M. Massaro, Ph.D., Ralph B. D'Agostino, Sr., Ph.D., and Lance D. Dworkin, M.D. for the CORAL Investigators
N Engl J Med 2014; 370:13-22
Prior to the CHORAL trial there has been widespread use of renal-artery stenting, despite the paucity of positive data and specifically clinical outcome data to justify this practice. The CHORAL trial sought to fill this void.
The CHORAL trial was a multicentre, open label, randomized controlled trial that compared medical therapy alone with medical therapy plus renal artery stenting in patients (>900) with renal-artery stenosis (>60%,<100% (angiographically)) and hypertension on at least 2 antihypertensive drugs, chronic kidney disease (at least stage 3) or both.
The following trials had multiple problems (as highlighted in an elegant review in the Cleveland Clinic Journal( http://www.ccjm.org/content/77/3/164.full.pdf+html). These trials had negative outcomes.
The DRASTIC (Dutch Renal Artery Stenosis Intervention Cooperative) had a small sample size 106 patients, not patients with resistant hypertension, balloon angioplasty without stenting, renal artery stenosis was defined as stenosis greater than 50% angiographically.
The STAR trial included 140 patients with a creatinine clearance of less than 80ml/min/1.73m2. At least a third of the patients had stenosis of 50-70%, 12/64 patients assigned to stenting had stenosis of <50%, only 72% of the patients in the stent group received a stent (intention to treat) and the trial was underpowered.
The ASTRAL trial had the primary outcome of change in renal function (806 patients). Problems in this trial included possible selection bias and 41% of the patients had renal artery stenosis of less than 70%.
The primary endpoint was a composite of death from cardiovascular and renal causes, myocardial infarction, stroke, hospitalization for congestive cardiac failure, progressive renal insufficiency and need for renal replacement therapy.
The secondary endpoints were made up of components of the primary endpoint.
- There was no significant difference in the primary endpoint, between the two groups, stenting plus medical therapy vs medical therapy alone ( 35.1% vs. 35.8%; P=0.58).
- There was no significant difference between any of the components of the primary endpoints.
- There was a very modest reduction in systolic blood pressure in the stenting arm (-2.3mmHg;P=0.03).
- There was an increase in the use of antihypertensive agents in both groups, however this did not differ significantly between the two groups.
The CHORAL trial adds to the dearth of positive outcome data for renal artery stenting, but the CHORAL trial was not without its flaws. Patients did not need to have resistant hypertension. The minimum kidney size was 7cm, and maybe at least 7.5 to 8cm would have been a more prudent size ( the kidney disease may have progressed to far, including hypertensive damage to the intra renal microvasculature. ). No patients with flash pulmonary oedema. Angiographic data was primaraly used to asses the severity of the renal artery lesions.
In a study by de Bruyne et al (http://circinterventions.ahajournals.org/content/3/6/537.full), the potential value of dopamine induced hyperemia with pressure gradient measurement was shown to have very significant predictive value as far as blood pressure reduction was concerned, but not renal function improvement. Despite this very a very small trial, which was not blinded, I think this is a very important hypothesis generating trial, which justifies incorporation into the next trial. It may be that the dopamine induced pressure drop, not only reflects the hemodynamic significance of the lesion, but that the intra renal dopamine reactivity may be a marker of intra renal vascular "health".
I think any future trial needs:
- Functional assessment of the lesion as a priority
- Only patients with resistant hypertension (or those unable to tolerate the side effects of the antihypertensive drug), flash pulmonary Oedema or progressive renal dysfunction should be included
- Only patients with a bilateral renal artery stenosis, unilateral stenosis in patients with only one kidney
- Minimum kidney size should be at least 7.5 to 8cm.
Until then I think the current guidelines are appropriate and should be followed strictly.