Q) I’ve heard a lot of references to “renal denervation” and its use for resistant hypertension. What is it? Does it work? Is it common in the US?
Renal denervation is a minimally invasive endovascular procedure that ablates (or disrupts) the renal nerves in and around the renal arteries with radiofrequency energy.5 Renal denervation has been approved in the US and other countries and is being used clinically in Europe, Canada, and Australia.6
It is thought that renal denervation interrupts the efferent and afferent signals that stimulate the renin-angiotensin-aldosterone system (RAAS) and regulate whole-body sympathetic nervous system activity.5 Similar to surgical sympathectomy, renal denervation should theoretically lower blood pressure. However, Ezzahti et al found that renin levels did not decrease in patients following renal denervation.7
Drug-resistant hypertension is defined as blood pressure that remains greater than 140/90 mm Hg despite treatment with three or more antihypertensive medications, including a diuretic.8 Patients with resistant hypertension have increased cardiovascular risk.9 Clinical trials of renal denervation have focused on treatment of resistant hypertension, in the hope of reducing the associated morbidity and mortality.
Results of the Symplicity HTN-3 trial, which assessed the safety and efficacy of renal denervation, were anxiously awaited, since prior trials yielded mixed results. Although the Symplicity HTN-1 and Symplicity HTN-2 studies demonstrated a possible benefit of renal denervation to lower office measured blood pressure, other studies did not show a decrease in BP in patients who had undergone renal denervation.6,7 These early trials, however, were small and did not randomize patients to a sham procedure.10
The Symplicity HTN-3 trial included 535 patients at 88 centers in the US. Patients were randomly assigned to receive either renal denervation plus baseline antihypertensive medications or a sham procedure plus baseline antihypertensive medications.
The researchers found that the sham procedure was just as effective as the “true” renal denervation in decreasing systolic blood pressure in patients with resistant hypertension.10 In other words, renal denervation did not demonstrate efficacy for this purpose.
In response to the results of this well-designed trial, the FDA has halted approval to perform renal denervation in patients with resistant hypertension in the US. However, clinical investigation will continue among subgroups of hypertensive patients or separate populations.
Despite a lack of efficacy, renal denervation does appear to be well tolerated, as evidenced by safety data from Symplicity HTN-3. —JK
Jessica Knight, ACNP
University of New Mexico Hospital, Albuquerque
REFERENCES
5. Esler MD, Krum H, Schlaich M, et al. Renal sympathetic denervation for the treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial. Circulation. 2012;126(25):2976-2982.
6. Thukkani AK, Bhatt LD. Renal denervation therapy for hypertension. Circulation. 2013;128:2251-2254.
7. Ezzahti M, Moelker A, Friesema E, et al. Blood pressure and neurohormonal responses to renal nerve ablation in treatment-resistant hypertension. J Hypertens. 2014;32(1):135-141.
8. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: Diagnosis, evaluation, and treatment: A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51(6):1403-1419.
9. Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125(13):1635-1642.
10. Bhatt DL, Kandzari DE, O’Neill WW, et al; Symplicity HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393-1401.
The author would like to thank Eric Judd, MD, of the University of Alabama at Birmingham, for his advice on the preparation of this response.