Percutaneous revascularization by angioplasty and stenting is associated with a high rate of technical success and artery patency; however, evidence of meaningful clinical benefit has been limited. The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial was a multicenter, randomized, unblinded, clinical endpoint study designed to determine whether, in addition to aggressive medical therapy, revascularization offered any important clinical benefit on renal function and other outcomes in patients with established renovascular disease.
Patients were screened for enrollment in the study if clinical findings, including refractory hypertension or unexplained renal dysfunction, suggested a diagnosis of atherosclerotic renal disease. These potential subjects underwent renal artery imaging by intra-arterial angiography, computed tomographic angiography, magnetic resonance angiography, or duplex ultrasonography at the discretion of the treating physician. Patients were eligible to participate if they had evidence of significant atherosclerotic renal artery stenosis in at least one renal artery, the lesion was considered by the treating physician to be suitable for potential percutaneous intervention, and in the opinion of the treating physician the evidence for clinical benefit was uncertain. Exclusion criteria included: previous revascularization for renal artery stenosis, known significant nonatheromatous cardiovascular disease, need for surgical renal artery revascularization, or belief on the part of the treating physician that the patient would have a high likelihood of definitely needing renal artery revascularization within 6 months. Eligible patients were randomized to receive percutaneous revascularization plus medical therapy vs medical therapy alone. Randomization stratified according to the serum creatinine level, estimated glomerular filtration rate (eGFR), severity of renal artery stenosis, kidney length on noninvasive imaging, and rate of progression of renal dysfunction over the previous year.
For patients assigned to undergo revascularization, the procedure was generally performed within 4 weeks of randomization. The precise revascularization procedure, including whether it was performed by angioplasty alone or with additional placement of a stent, was determined by the treating interventionalist. Distal protection devices were not used. Patients in both groups received aggressive medical therapy aimed at controlling the progression of atherosclerosis and renal dysfunction. While the exact protocol was set by the local practitioner, in general, medical treatment included use of statin-based lipid lowering therapy, optimal blood pressure control, and antiplatelet agents. Follow-up visits were scheduled at 1–3 months, 6–8 months, at 1 year, and yearly thereafter for 5 years. The primary outcome was the change in renal function, assessed by measuring the mean slope of the reciprocal of the serum creatinine over time. Secondary and other tracked outcomes included: blood pressure, time to first renal event (new onset of acute kidney injury, initiation of dialysis, renal transplantation, nephrectomy, or death from renal cause), time to first cardiovascular event (myocardial infarction, stroke, hospitalization for cardiovascular cause, intervention for peripheral artery disease, or death from cardiovascular cause), total mortality, treatment complications, and serious adverse events. All analyses were performed according to intention-to-treat principle with the use of all available data through the maximum follow-up of 5 years.
From September 2000 through October 2007, 806 participants (mean age 70 years) were randomized at 57 hospitals (53 in the United Kingdom, 3 in Australia, and 1 in New Zealand). Overall, 59% of patients had renal artery stenosis of at least 70%, and 60% had a serum creatinine of at least 1.7 mg/dL. Mean baseline eGFR was about 40 mL/min, mean urinary protein was approximately 500–700 mg/d, and mean blood pressure was approximately 150/76 mm Hg on a mean of 2.8 antihypertensive medications. Overall, about 92% of subjects were on antiplatelet agents, and 80% were on lipid lowering therapy (96% of whom were on a statin).
In the revascularization group, the procedure was attempted in 335 of the 403 enrolled (83%) patients and was considered a technical success in 95% of procedures attempted. The vast majority of revascularized patients (95%) received a stent. In the medical therapy alone group, 24 patients (6%) required revascularization after a mean of 601 days. After 1 year in both the revascularization plus medical therapy and the medical therapy alone group, the proportion of patients receiving lipid lowering medications and antiplatelet agents was similar to baseline. After a year, the average number of antihypertensive agents used was somewhat higher for patients in the medical therapy alone group (2.97 vs 2.77 medications [P=.03]). In addition, slightly more patients in the revascularization group were receiving renin-angiotensin blockers both at baseline (47% vs 38%, P=.02) and after 1 year (50% vs 43%, P=.05).
During the 5 years of follow-up, the overall mean slope of the reciprocal of the serum creatinine concentration (primary endpoint) was not significantly different between the two groups, and there was no difference in change in serum creatinine over time between the two groups. Even when per protocol analysis compared only those who actually had revascularization vs those who did not, there was no difference in the primary outcome. There were also no differences in the primary endpoint in any of the protocol specified subgroups, including those defined by renal function, degree of stenosis, kidney length, and previous rate of renal function deterioration. In terms of blood pressure, over the 5-year follow-up period, systolic blood pressure decreased in both groups, without any significant difference between groups, and diastolic blood pressure actually decreased to a somewhat greater degree in the medical therapy alone group. During follow-up, the number of renal events and the time to first renal event were not different between the two groups; the incidence of new end-stage renal disease was 8% in both groups. Finally, there was no significant difference in the incidence of cardiovascular events or total mortality (103 deaths in the revascularization group vs 106 deaths in the medical therapy alone group). In total, there were 31 serious complications (in 23 patients) within 1 month of revascularization.
In patients with documented atherosclerotic renal artery stenosis receiving aggressive medical therapy, there is no discernable clinical benefit associated with percutaneous revascularization with respect to renal function, blood pressure, renal or cardiovascular events, or mortality. In addition, revascularization carries with it significant risk.—ASTRAL Investigators. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009;361(20):1953–1962.