CardioExchange Archive

We welcome Philip A. Kalra, MD, one of the investigators and the lead nephrologist for the UK-based ASTRAL trial, to talk about the group’s article in the November 12 issue of the New England Journal of Medicine: Revascularization versus Medical Therapy for Renal-Artery Stenosis (N Engl J Med 2009; 361:1953). We asked him our questions and encourage you to ask yours.

CardioExchange Editors: In ASTRAL, the rate of decline in renal function for patients with renal-artery stenosis (RAS) did not differ significantly between those randomized to percutaneous revascularization plus medical therapy and those randomized to medical therapy alone. How do you answer the criticism that the study explicitly excluded patients whose doctors felt that stenting would definitely help them?

Kalra: First, although clinicians were permitted to exclude patients they thought would definitely require revascularization, there was no explicit guidance to do that, nor any central adjudication. Second, not all clinicians have the same approach. For example, I was happy to enroll patients with critical bilateral RAS, provided that they had no evidence of deteriorating renal function. Therefore, the ASTRAL population is likely to represent a heterogeneous group of patients with significant anatomical RAS for whom it’s genuinely unclear whether revascularization will improve clinical outcomes. That’s a real-life question. Nonetheless, given the patient exclusions that did occur, ASTRAL probably had a high proportion of largely asymptomatic subjects, such as those being investigated for chronic kidney disease with hypertension, as opposed to more acute presentations such as heart failure or acute kidney injury. For example, only 12% of the ASTRAL population had clear evidence of decline in renal function prior to randomization.

CardioExchange Editors: Clinicians in the U.S. are starting to screen asymptomatic patients for RAS, with a plan for stenting in those who have “significant” disease. Are your results relevant to these patients?

Kalra: The ASTRAL results are probably more relevant to these patients than to any others. That includes people for whom RAS is an incidental finding (for example, during coronary angiography) and outpatients who are being investigated for stable chronic kidney disease, hypertension, or both. For such groups, I think that the ASTRAL data conclusively show no benefit of revascularization — in terms of renal function, blood-pressure control, adverse renal and cardiovascular events, or mortality.

CardioExchange Editors: Your group reported that the mean percent-stenosis of the treated arteries was 76% and that roughly 60% of patients had RAS >70%. But might many of those stenoses have  been hemodynamically unimportant?

Kalra: I have to acknowledge that there was no core-lab assessment of the angiograms, and so no robust validation of the percent-stenosis data. Given the prevalence of CT and MR angiography late in the trial, the degree of RAS was probably overestimated in some patients (a well-known problem with MRA assessment). Indeed, about 13% of patients randomized to revascularization did not undergo the procedure because the degree of RAS was found to be insignificant at definitive on-table angiography. Although we did not assess the hemodynamic significance of RAS lesions, the value of resistive-index assessment remains unclear, and transstenotic pressure gradients are not routinely measured in the UK. Nonetheless, some ASTRAL subjects are likely to have had hemodynamically insignificant lesions. But bear in mind that many such lesions are still being revascularized in clinical practice (witness so-called “drive-by stenting” during coronary angiography).

CardioExchange Editors: Given the ASTRAL findings, will the British National Health Service continue to support stenting?

Kalra: To date there has been no call for our major treatment-review bodies, such as the National Institute for Clinical Excellence (NICE), to review UK revascularization practice. That may be because renal revascularization is relatively uncommon in the UK — currently, about 250 to 600 total cases per year.

CardioExchange Editors: What would be your recommendation to the National Health Service, should NICE decide to revisit this matter?

Kalra: I would recommend that the option to perform renal revascularization in particular clinical subgroups be retained. Although evidence of benefit is limited, clinical consensus would support revascularization in some patients who have anatomically significant RAS and who present with one of the following characteristics:

• acute kidney injury
• sudden-onset heart failure
• critical bilateral RAS (or unilateral, if supplying a sole functioning kidney)
• clear evidence of deteriorating renal function, with no other cause identified, prior to consideration of stenting
• very severe hypertension that is unresponsive to multiple medications
• possibly, chronic heart failure

However, we need more evidence in some of these clinical scenarios. The forthcoming CORAL trial will provide further insights, and eventually a meta-analysis of data from both ASTRAL and CORAL may be a powerful resource. For now, I would suggest that U.S. regulatory bodies consider making recommendations similar to those I’ve offered here.
CardioExchange Editors: We’re very curious to hear from the CardioExchange community: What questions or perspectives do you have on the ASTRAL trial and its implications for clinical practice?