S T E V E N D. H O C H M A N
We found no evidence of a worthwhile clinical benefit after revascular-ization in patients with atherosclerotic renal artery stenosis.
—ASTR AL Investigators1
Research Question: Should patients with renal artery stenosis be treated with revascularization or medical therapy?1
Funding: The Medical Research Council of the United Kingdom, a publicly funded agency; the charity Kidney Research UK; and Medtronic, the manu-facturer of the stents used in the study.
Year Study Began: 2000
Year Study Published: 2009
Study Location: 53 hospitals in the United Kingdom, 3 in Australia, and 1 in New Zealand.
Who Was Studied: Adult patients with clinical signs of atherosclerotic reno-vascular disease (e.g., “uncontrolled or refractory hypertension or unexplained renal dysfunction”) were screened with renal artery imaging. Those found to have “substantial atherosclerotic stenosis in at least one renal artery”1 were eli-gible for enrollment.
Who Was Excluded: patients with a history of renal artery revascularization or planned revascularization, and those likely to require a revascularization within 6 months. Those with nonatheromatous cardiovascular disease were also excluded. In addition, patients were excluded if the treating physician felt that either revascularization or medical management was clearly indicated.
How Many Patients: 806
Study Overview: See Figure 17.1 for a summary of the study’s design.
Study Intervention: patients randomized to the revascularization group received renal artery revascularization as soon as possible. Revascularization was accomplished with “angioplasty either alone or with stenting” at the discre-tion of the treating physician. patients in both groups were medically managed with statins, antiplatelet agents, and antihypertensives at the discretion of the treating physician and “according to local protocols.”
Randomized
Patients with Renal Artery Stenosis
Revascularization
+ Medical Therapy Medical Therapy Alone
Figure 17.1 Summary of the Study Design.
Revascularization versus Medical Therapy for Renal Artery Stenosis 111
Follow-Up: planned for 5 years; the median follow-up was 33.6 months.
Endpoints: primary outcome: Change in renal function. Secondary out-comes: Blood pressure control; all-cause mortality; time to first renal event (including new onset acute kidney injury, initiation of dialysis, renal transplant, nephrectomy, or death from renal failure); time to first cardiovascular event (including myocardial infarction; hospitalization for angina, stroke, coronary or peripheral artery revascularization procedure; fluid overload or cardiac fail-ure, or death from cardiovascular causes).
RESULTS
• At baseline, 59% of patients had >70% stenosis of at least one renal artery, and 60% had a serum creatinine >1.7 mg/dL; the estimated glomerular filtration rate (eGFR) was <50 μmol/L for 75% of patients.
• In the revascularization group, 79% of patients received a successful revascularization procedure at a median of 32 days following randomization; 6% of patients in the medical therapy group crossed over and underwent revascularization at a median of 601 days following randomization.
• There were no statistically significant differences in the change in renal function between the two groups in the intention-to-treat or per-protocol analyses (Table 17.1); subgroup analyses based on serum creatinine level, severity of stenosis, kidney length, and rate of disease progression did not yield any significant trends (i.e., it did not appear that revascularization was beneficial among any subgroups).
• Blood pressure improved in both groups with no between-group differences, though patients in the medical therapy group
received slightly more antihypertensives compared to those in the revascularization group (2.97 versus 2.77, P = 0.03).
• There were no between-group differences in the risk of renal events, cardiovascular events, or all-cause mortality (Table 17.1).
• For patients who underwent revascularization, 9% experienced an adverse event within 24 hours of the procedure; half of these events were considered serious complications.
Criticisms and Limitations: patients were excluded from the study if their treating physician felt that renal artery revascularization was clearly indicated.
Thus, there may have been a selection bias such that patients less likely to benefit from revascularization were disproportionately included in the study.
however, there is no evidence that treating physicians can successfully select which patients are likely to benefit from renal artery revascularization.
Additionally, 41% of enrolled patients had a renal artery stenosis <70%, which may not be severe enough to cause complications such as hypertension or renal dysfunction. It is possible that the results of ASTRAL would have been different had more patients with severe stenosis been included. However, a post hoc analysis of this study and subsequent studies involving patients with more severe stenosis have also failed to demonstrate a benefit with revascularization (see the following section).
Other Relevant Studies and Information:
• Observational studies have demonstrated improvements in mortality, renal disease progression, and blood pressure control in patients selected to undergo renal artery revascularization based on specific clinical indications such as refractory hypertension, flash pulmonary edema, resistance to ACe inhibitors, or refractory heart failure.2,3
Table 17.1 Summary of Key Findings
Variable Revascularization Medical Therapy P Value Renal Function
Change in Reciprocal
of Creatininea −0.07*10-3 L/μmol/yr −0.13*10-3 L/μmol/yr 0.06 Change in
Creatinineb +7.47 µmol/liter/yr +10.52 µmol/liter/yr
Total Renal events 22% 22% 0.97
Acute Kidney Injury 7% 6% not reported
end-Stage Renal
Disease 8% 8% not reported
Cardiovascular events 49% 51% 0.96
overall Survival 60% 57% 0.46
a Change in reciprocal of creatinine is assessed because it has a linear relationship with the estimated gFR. Large negative values of this variable indicate a greater worsening of renal function (i.e., renal function decreased nonsignificantly faster in the medical therapy group).
b Large positive values of this variable indicate a greater worsening of renal function (i.e., renal function decreased nonsignificantly faster in the medical therapy group).
Revascularization versus Medical Therapy for Renal Artery Stenosis 113
however, because patients in these studies were not randomized, the results are inconclusive.
• Other major randomized trials of renal artery revascularization are consistent with ASTRAL. Most notably, the CoRAL trial randomized 947 patients with severe renal artery stenosis (>80% stenosis or >60%
stenosis with a systolic pressure gradient of >20 mm Hg) plus either refractory hypertension or chronic kidney disease (eGFR of <60 mL/
min/1.73m2) to renal artery revascularization or medical therapy and found no benefit with revascularization.4
• National Kidney Foundation guidelines from 2004 state that there is insufficient evidence to recommend for or against revascularization procedures in patients with renal artery stenosis, and they recommend a case-by-case evaluation with a kidney disease specialist.5 however, as increasing evidence mounts that revascularization is ineffective in most patients, these guidelines may require modification.6
Summary and Implications: The ASTRAL trial, as well as other random-ized trials, demonstrate that for most patients with renal artery stenosis medi-cal therapy is as effective as revascularization. Guidelines from the National Kidney Foundation recommend that the decision about whether to treat patients with renovascular disease with revascularization versus medical ther-apy should be made on a case-by-case basis. however, present data indicate that medical therapy is at least as effective as revascularization for most patients.
Further research will be needed to determine which subgroups of patients, if any, benefit from revascularization.
CLINICAL CASE: MANAGEMENT OF RENAL ARTERY STENOSIS
Case History:
A 65-year-old man with a past medical history of prehypertension, diabetes, and stable angina and a 35 pack-year smoking history is found to have a blood pressure of 155/95 on physical examination and a serum creatinine of 1.8 mg/
dL. Typically, his blood pressure is 130/80 and his creatinine is 1.0 mg/dL.
The patient’s physician initiates him on amlodipine and when he returns one month later he is found to have a blood pressure of 162/98 and a serum cre-atinine of 2.1 mg/dL. Renal artery imaging is ordered. The patient is found to have right-sided renal artery stenosis >70%.
References
1. ASTRAL Investigators et al. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009;361:1953.
2. Kalra pA et al. The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease. Catheter Cardiovasc Interv. 2010;75:1.
3. gray Bh et al. Clinical benefit of renal artery angioplasty with stenting for the control of recurrent and refractory congestive heart failure. Vasc Med. 2002;7:275.
4. Cooper CJ et al. Stenting and medical therapy for atherosclerotic renal-artery ste-nosis. N Engl J Med. 2013;370(1):13–22.
5. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical prac-tice guidelines on hypertension and antihypertensive agents in chronic kidney dis-ease. Am J Kidney Dis. 2004;43:S1–S290.
6. Bitti JA. Treatment of atherosclerotic renovascular disease. N Engl J Med. 2014;
370:78–79.
Based on the results of the ASTRAL trial, how should this patient be managed?
Suggested Answer:
This patient has renal artery stenosis complicated by hypertension and kid-ney disease. The ASTRAL trial and other randomized trials do not suggest that patients with these conditions are likely to benefit from revascularization.
Thus, it would be appropriate to treat him medically with statins, antiplate-let agents, and antihypertensives. Further research will be needed to deter-mine whether subgroups of patients with severe disease might benefit from revascularization.