Revascularization versus medical therapy for renal-artery stenosis. The ASTRAL Investigators. The New England Journal of Medicine 2009; 361: 1953—1962

Abstract

Study objective: The objective of ASTRAL was to determine whether percutaneous revascularization combined with medical therapy compared to medical therapy alone improves renal function and other outcomes, such as blood pressure, time to first renal event, time to first major cardiovascular event, and mortality. Study population: ASTRAL enrolled 806 patients with atherosclerotic renovascular disease from 57 centers. Patients were screened if treating clinicians felt they had clinical features suggestive of underlying atherosclerotic renovascular disease (i.e. hypertension refractory to medical therapy, or renal impairment as suggested by laboratory measurements). All patients had to have an imaging modality (i.e. computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or renal artery ultrasound). This imaging had to convey that the patient had ‘substantial’ anatomical atherosclerotic stenosis in at least one renal artery that was suitable for endovascular therapy. Also, the treating clinician had to be ‘uncertain’ that the patient would benefit from revascularization. Fifty-nine percent of patients were reported to have renal artery stenosis of > 70%, and 60% had a serum creatinine of ≥ 150 mmol per liter. Design and methods: ASTRAL was a randomized, unblinded study of patients with atherosclerotic renal artery disease who were assigned to percutaneous revascularization plus best medical therapy or best medical therapy alone. The primary outcome of the ASTRAL trial was the change of renal function over time, as determined by the mean slope of the reciprocal of serum creatinine. Secondary outcomes included blood pressure, time to first renal event (defined as: new onset of kidney injury, dialysis, renal transplantation, nephrectomy, or death from renal failure), time to first major cardiovascular event (defined as: myocardial infarction, stroke, death from cardiovascular cause, hospitalization for angina, fluid overload or congestive heart failure, coronary artery revascularization, or another peripheral arterial procedure), and all-cause mortality. Randomization was 1:1 via computer algorithm and was stratified by serum creatinine, glomerular filtration rate (GFR), severity of renal artery stenosis, kidney length on ultrasound, and rate of progression of renal impairment. Patients who were assigned to the revascularization plus medical therapy arm underwent percutaneous revascularization within 4 weeks. The procedure type (angioplasty alone or with stenting), was left to the discretion of the local operator. Distal protection devices were not used. Medical therapy in both arms consisted of antihypertensive drugs, statins, and antiplatelet agents. The trial was powered to detect a 20% reduction in the mean slope of the reciprocal of serum creatinine. Based on low crossover rates, it was determined that at least 750 patients would have to be enrolled. Analysis was by intention to treat. Continuous variables were subject to repeated measures analysis. Time-to-event data were expressed via Kaplan Meier curves and compared via log-rank testing. Prespecified subgroup analyses included baseline serum creatinine, GFR, severity of renal artery stenosis, kidney length, and progression of renal disease. Results: Of the 806 patients included, 403 were randomized to the revascularization arm and 403 to medical therapy only. The median follow-up was 34 months. Only 337 (83%) patients randomized to revascularization underwent the procedure, whereas 24 patients (6%) randomized to the medical therapy arm underwent revascularization. The number of antihypertensive medications used was greater in the medical therapy group than in the revascularization group at the 12-month follow-up: 2.97 versus 2.77 ( p = 0.03). The mean slope of the reciprocal of the serum creatinine concentration was —0.07 × 10— 3 liters per micromole per year in the revascularization group versus —0.13 × 10—3 liters per micromole per year in the medical-therapy group (difference of 0.06 × 10 —3 liters per micromole per year) (95% confidence interval [CI], —0.002 to 0.13, p = 0.06) with a trend favoring revascularization. After 5 years of follow-up, there was a trend toward lower mean systolic blood pressure (1.6 mmHg lower, p = 0.06) in the revascularization group. However, the mean diastolic blood pressure was significantly lower in the medical therapy group at long-term follow-up (divergence of slope of mean diastolic blood pressure: 0.61 mmHg per year, p = 0.03). There was no significant difference between renal events, time to first renal event, acute kidney injury, or development of end-stage renal disease in either group. Further, there was no difference in major cardiovascular events or overall survival in either group. The periprocedural complication rate within the revascularization group was 9% (31/359 patients). Fifty-five out of 280 patients (20%) had an adverse event by 1 month post procedure. Overall, there were 31 serious complications of revascularization in 23 patients. Per protocol analysis of patients suggested that there was no significant difference in outcomes between patients who received revascularization versus medical therapy. No differences between treatment groups were identified in any of the pre-specified subgroup analyses. Conclusions: Renal artery stenting combined with medical therapy did not improve renal function compared to medical therapy alone in patients with atherosclerotic renal artery disease.