Stenting atherosclerotic renal arteries: Time to be less aggressive
ABSTRACTPercutaneous intervention has become very popular for treating atherosclerotic renal artery stenosis, as the use of stents has boosted the rate of technical success and as more cases are being discovered incidentally during angiography of the coronary or other arteries. Yet randomized trials indicate that the procedure does little in terms of controlling blood pressure and may actually harm as many patients as it helps in terms of renal function. Needed are better ways to predict which patients will benefit and better ways to prevent adverse effects such as atheroembolism.
KEY POINTS
- Two large randomized trials of intervention vs medical therapy showed negative results for intervention. A third trial is under way.
- Intervention is not recommended if renal function has remained stable over the past 6 to 12 months and if hypertension can be controlled medically.
- The best evidence supporting intervention is for bilateral stenosis with “flash” pulmonary edema, but the evidence is from retrospective studies.
- Stenosis by itself, even if bilateral, is not an indication for renal artery stenting.
ASTRAL: Also no clear benefit
In the international, multicenter ASTRAL trial,6,7 806 patients with at least one stenotic renal artery considered suitable for balloon angioplasty, stenting, or both7 were randomized to undergo intervention or medical management. Hypertension treatment was not specified by a protocol. The mean estimated GFR was 40 mL/min. Most patients (95%–96%) were on statin therapy. The primary outcome was the rate of decline of renal function over time. Secondary outcomes included blood pressure control, renal events, cardiovascular events, and death.
Results. At a mean follow-up of 33.6 months (range 1–4 years), no difference was noted between treatment groups in decline in renal function or blood pressure control at 1 year. Renal function worsened slightly in both groups.
The decline in renal function over time, calculated as the mean slope of the reciprocal of the serum creatinine level over time, was slightly slower in the revascularization group, but the difference was not statistically significant (−0.07 × 10−3 vs −0.13 × 10−3 L/μmol/year, P = .06). This difference did not appear until the last year of the study. There was no difference in the number of patients whose renal function improved or declined during the study.
There was no difference in the rate of any secondary outcome. The medical management group required a slightly higher number of antihypertensive drugs, reaching statistical but not clinical significance (2.97 vs 2.77 drugs, P = .03). More people in the revascularization group were taking ACE inhibitors or angiotensin receptor blockers. There was no difference in the number of patients on any antihypertensive therapy (97% vs 99%). Interestingly, amputations were more common in the revascularization group, occurring in 42 (12%) of the 386 patients in the revascularization group vs 29 (7%) of the 395 patients in the medical group (P = .04).
Seventeen percent of patients randomized to intervention did not have the procedure done. An as-treated analysis of the 317 (83%) patients randomized to revascularization who did receive it showed no differences in outcomes.
There were no differences in outcomes among specific, predefined subgroups based on severity of stenosis at baseline, renal length, baseline estimated GFR, baseline serum creatinine, and rate of progression of renal dysfunction before randomization.7
Comments. ASTRAL contradicts previous nonrandomized studies that suggested that rapidly declining renal function (loss of 20% in 1 year) predicts response to intervention. Considering the large number of patients with unilateral disease in the study, it would be interesting to see what effect stenting had on patients with both severe disease and declining renal function.
ASTRAL has been criticized because it lacked a central laboratory to interpret the severity of stenosis, it did not use a standardized intervention technique (5% of patients underwent angioplasty without stents, although this did not affect outcomes7), and patients were enrolled only if the clinician involved in the case was uncertain of the appropriate management.
This last issue raises the concern for selection bias toward inclusion of more difficult cases that may not respond to intervention. But these shortcomings are not serious enough to negate the fact that preliminary results from the largest randomized controlled trial to date confirm conclusions of other randomized trials, ie, that intervention in renal artery stenosis yields no benefits over medical management in most patients.
Based on the results of STAR and ASTRAL, the practice of indiscriminately revascularizing stenosed renal arteries without strong evidence that the procedure will provide a clinical benefit is no longer tenable. The challenge is to identify those few patients who will respond, and to intervene only on them. Unfortunately, none of the subgroups from ASTRAL helped characterize this population.
CORAL: A large trial is ongoing
The Cardiovascular Outcomes in Renal Artherosclerotic Lesions (CORAL) trial,8 an ongoing multicenter randomized controlled trial in the United States, may be of additional help.
Unlike ASTRAL, CORAL is studying patients who have difficult-to-control hypertension (systolic blood pressure ≥ 155 mm Hg on two or more drugs).8 Chronic kidney disease is not an exclusion criterion unless the serum creatinine concentration is greater than 3.0 mg/dL.
CORAL is using a standardized medical protocol to control blood pressure. In addition, use of embolic protection devices during stenting is encouraged. Hopefully, the large size (a goal of 1,080 patients) and the inclusion of patients with more marked hypertension will address the utility of intervention in higher-risk populations with renal artery stenosis.
RECOMMENDED APPROACH TO INTERVENTION IN RENAL ARTERY STENOSIS
As we wait for CORAL to be completed, we have two modern-era randomized controlled trials that leave us with fewer indications for renal intervention. Table 2 lists commonly cited indications for intervention in renal artery stenosis and the evidence to support them. As most of these are based on retrospective data or have conflicting support in the literature, their utility remains in question. At this point we can safely recommend:
- Patients with preserved or even decreased but stable renal function will not likely have a benefit in renal function after intervention.
- Patients with resistant hypertension may benefit.
- The best evidence supporting intervention is for bilateral stenosis with flash pulmonary edema, but the evidence is from retrospective studies.
- Stenting in bilateral disease without another indication has no apparent benefit.
- Declining renal function is not a guarantee of success.
- It is unclear if patients with severe bilateral stenosis or severe stenosis to a solitary functioning kidney with declining renal function will benefit. Anecdotally, they do respond more often, but as with many other indications for intervention that have gone by the wayside, this may not bear out when studied properly.
As the utility of intervention narrows, the scope of practice for such interventions should narrow accordingly. Attention should now be focusing on clinical, rather than radiographic, indications for intervening on renal artery stenosis.
Therefore, the decision to intervene must not be made solely by the interventionalist. A multidisciplinary approach should be adopted that at the very least includes the input of a nephrologist well versed in renal artery stenosis. In this way, the clinical risks and benefits of renal intervention can be discussed with the patient by providers who are likely to be involved in their care should renal function or hypertension fail to improve afterward.
