Renal denervation as a treatment for drug-resistant hypertension—already approved in many parts of the world and seemingly headed for approval here in the U.S.—remains a controversial topic with a lot of uncertainty. To shed some light on the issue, CardioExchange’s Dr. John Ryan posed some questions to Dr. Murray David Esler, a pioneer in the field.
Dr. Ryan: In the two-year follow up from Symplicity HTN-1 and Symplicity HTN-2, there was sustained reduction in systolic blood pressure of 25 to 30 mmHg. For how long do you suspect this reduction can be maintained? Does re-innervation of the kidneys result in the blood pressure increasing again or will the kidneys be more resistant?
Dr. Esler: The patient with the longest follow up is now at 5 1/2 years. In this patient, and others with long-term follow up, there has been no loss of antihypertensive effect of renal denervation over time. It was anticipated that sympathetic reinnervation of the kidneys might perhaps cancel out the BP lowering effects, but the stability of blood pressure lowering in these patients argues against substantial reinnervation. It would be possible to test for reinnervation, using renal norepinephrine spillover measurements, which quantified the initial renal denervation, but this has not been done to-date.
Dr. Ryan: The data on renal artery denervation currently demonstrate the reduction in blood pressure, but we have no published clinical endpoints (heart attack, strokes, mortality): What effect would you expect devervation to have on real patient outcomes?
Dr. Esler: If it can be maintained, the degree of blood pressure reduction achieved with renal denervation in drug-resistant hypertension—approximately 30 mm Hg systolic—would predict a substantial reduction in risk of cardiovascular endpoints. With a starting systolic BP of 180 mm Hg, this would be perhaps a 40% reduction in risk. This does remain conjectural, although likely, in the absence of renal denervation trials which have directly tested for reduction in clinical outcomes.
Dr. Ryan: From a societal standpoint, introducing healthy lifestyle and weight loss is likely preferable to renal artery denervation for reducing hypertension. However, practitioners may be tempted to choose denervation with the view that behavioral modification is so difficult. Are you concerned that patients may undergo renal artery denervation before other treatments are tried? How would you prevent any overuse, if at all?
Dr. Esler: Non-pharmacologic antihypertensive measures must remain the starting point for patients with hypertension, but will often not be enough. Renal denervation should be reserved for patients in whom behavior modification combined with adequate and skillful antihypertensive drug prescribing cannot achieve BP reduction to target. There are no clinical trial data to support renal denervation in hypertension outside of this setting. In countries where the “genie is out of the bottle”, and clinical use is authorized, prevention of overuse will be difficult. In some instances government regulations will confine the use of renal denervation to drug-resistant hypertension. Insurer or governmental reimbursement rules should be framed to prevent overuse.
Dr. Ryan: Many expect this intervention to be a ‘cure’ for hypertension. Based on your experience, do you believe that this procedure will ultimately result in many previously hypertensive patients no longer requiring antihypertensive medication?
Dr. Esler: The available evidence is that renal denervation will not cure drug-resistant hypertension, which of course would be hoping for too much. Approximately 40% to 50% of patients do achieve target BP (140 mm Hg systolic), but this requires the denervation procedure plus continuation of perhaps 3-4 of their tablets. The denervation is ancillary to antihypertensive medication. I share a dream with some other researchers that renal deveration might in fact cure milder grades of hypertension, so that drug-naive patients might never have to receive medication. We are just beginning to establish trials to test this, but the idea is perhaps fanciful.