Renal sympathetic denervation for treatment of resistant hypertension

The challenge

It is estimated that between 30 and 40 percent of adults are currently affected by hypertension. Although there are numerous safe and effective antihypertensive drugs available for treatment, from 20 to 30 percent of adults being treated do not have adequate control of their hypertension, and this number is growing.

Approximately 13 percent of adults with hypertension are considered to be treatment resistant because their hypertension is uncontrolled despite taking a three-drug regimen that includes a diuretic. Not surprisingly, factors such as cost, adverse effects, drug interactions, and noncompliance play a role in limiting the effectiveness of current therapies.

Looking back in time for answers

The search for a solution to this dilemma led researchers to look back in history. A 1931 publication documented that surgically disrupting the sympathetic nerves connecting the kidneys with the central nervous system, via a procedure called splanchnicectomy, helped reduce blood pressure. The use of surgical procedures (splanchnicectomy and even nephrectomy) to treat severe hypertension continued through the early 1950s, until medical therapies became widely available.

Decades later, with the incidence of drug-resistant hypertension rising and the availability of less invasive techniques, researchers began looking at interventions with renewed interest. With catheter-delivered radiofrequency ablation already in use for the treatment of complex ventricular arrhythmias, certain cancers and other disorders, this option is now being studied as a possible intervention for resistant hypertension.

How catheter-based denervation works

During a catheter-based denervation procedure, the physician places a standard 6F sheath in the femoral artery with the patient under local anesthesia, and advances an electrode-tipped catheter into the renal artery with fluoroscopic guidance. Once positioned, the catheter delivers low-level radiofrequency energy through the renal artery wall to disrupt the surrounding renal nerves, working in a spiral pattern to avoid single segment injury. Both left and right renal arteries are treated, and the total procedure time is 30 to 40 minutes.

Early results

Early studies in animals and in humans suggested that the renal nerves play a role in blood pressure regulation. A series of pilot studies as well as a clinical trial (Symplicity HTN-2) involving patients with uncontrolled hypertension then showed that a catheter-based system can safely denervate the kidney and produce notable and sustained reductions in blood pressure.

The Symplicity HTN-2 trial, conducted in Australia and Europe, involved 106 patients who were randomly assigned to either the treatment group (receiving renal denervation and maintenance of baseline medications) or the control group (maintenance of baseline medications). Participants were patients with uncontrolled hypertension who had office-based systolic blood pressure of 160 mm Hg or higher despite treatment with three or more antihypertensive medications.

Published in November 2010, the trial showed a -32/-12 mm Hg change for the renal denervation group at six months, compared with a +1/0 mm Hg change for the control group (P<.001), with no adverse device effects and no serious device- or procedure-related complications.

These blood pressure changes, observed six months after intervention, have also been observed to persist at two years in the latest follow-up study. Additionally, data from these studies suggest an improvement in glycemic control with the intervention.

What's next?

Mayo Clinic has been selected to participate in the Symplicity HTN-3: Renal Denervation in Patients With Uncontrolled Hypertension trial, a multicenter, prospective, single-blind, randomized controlled study of the safety and effectiveness of renal denervation in patients with uncontrolled hypertension.

This study will enroll approximately 1,060 subjects into the screening phase, of whom approximately 530 will be randomized. Subjects who meet all criteria after the screening period will undergo a renal artery angiogram to evaluate renal artery anatomy, and eligible subjects will be randomly assigned at a 2-1 ratio to either the intervention group or the control group.

Symplicity HTN-3 trial

Inclusion criteria

  • Age 18-80 years
  • Office systolic blood pressure ≥160 mm Hg on ≥3 medications, including a diuretic
  • Glomerular filtration rate >45 mL/min
  • No history of renal artery stenosis

Exclusion criteria

  • Type 1 diabetes mellitus
  • Chronic oxygen use
  • Primary pulmonary hypertension
  • Pregnancy
  • Known secondary cause of hypertension

Patient flow

  • Two screening visits over two weeks to confirm resistant hypertension
  • Angiography in catheterization lab
  • Randomization on table to denervation or angiography alone (2-to-1)
  • Follow-up visits at one, three and six months
  • Three to four more visits over next two years
  • Sham group offered denervation at six months

Intervention group subjects will receive the renal denervation procedure and continue baseline antihypertensive medications without changes for six months.

Control group subjects will undergo angiography alone (sham procedure) and continue baseline antihypertensive medications without changes for six months, after which they will have the option to have the renal denervation procedure.

Subjects will be unaware of their randomization assignment because of a combination of conscious sedation, sensory isolation, and lack of familiarity with procedural details and duration.

New data from the Symplicity HTN-3 trial will help establish whether therapeutic renal denervation using a catheter-based approach is a safe and effective therapy for patients with uncontrolled hypertension.

To schedule a consultation for evaluation and treatment of a patient with resistant hypertension, please call 507-284-9991. To enroll a patient in the Symplicity HTN-3 study, please call 507-266-3802.

Points to remember

  • Between 20 and 30 percent of adults being treated for hypertension with medications do not achieve adequate blood pressure control.
  • Researchers are exploring whether ablation of the renal sympathetic nerves using catheter-delivered radiofrequency energy is an effective intervention for uncontrolled hypertension.
  • Mayo Clinic is enrolling patients in the Symplicity HTN-3 trial, a multicenter study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension.