SYMPLICITY I: One- and Three-Year Results Following Sympathetic Renal Denervation in Refractory Hypertension - SYMPLICITY I

Sep 03, 2013
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
Ardian Inc., Palo Alto, CA
Date Published:
01/01/2011
Date Updated:
09/03/2013
Original Posted Date:
09/03/2013
References

Description:

The Symplicity® catheter system has been shown in first-in-man studies to be an effective tool for radiofrequency (RF) ablation of the renal sympathetic nervous system in patients with refractory hypertension. The current trial sought to study the efficacy of blood pressure (BP) lowering with this approach at 12 months.

Hypothesis:

RF ablation resulting in renal sympathetic denervation would be associated with a significant reduction in systolic BP (SBP) and diastolic BP (DBP) in patients with refractory hypertension at 12 months.

Study Design

Patients Enrolled: 153
Mean Follow Up: 36 months
Mean Patient Age: 57 years
Female: 39%

Patient Populations:

  • Severe resistant hypertension (SBP ≥160 mm Hg on three or more antihypertensive medications, including a diuretic)
  • Glomerular filtration rate ≥45 ml/min

Exclusions:

  • Known secondary causes of hypertension
  • Type 1 diabetes mellitus
  • Currently on minoxidine, clonidine, or rilmenidine
  • Renovascular abnormalities, such as significant renal artery stenosis, prior renal stenting or angioplasty, or dual renal arteries
  • Pregnancy

Primary Endpoints:

  • Change in SBP and DBP at 12 months, as compared with baseline

Drug/Procedures Used:

Symplicity® catheter system is used to conduct 4-6 RF ablations in each renal artery.

Concomitant Medications:

Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (92%), beta-blockers (82%), calcium-channel blockers (74%), and diuretic (93%)

Principal Findings:

A total of 153 patients with resistant hypertension were enrolled. The mean baseline BP was 176/98 mm Hg. The mean number of antihypertensive medications at baseline was 5.1 per patient. The mean procedure time was 38 minutes, with an average of four ablations in each renal artery. A 6F guide was utilized in 55 patients and 8F in 98 patients. Complications were noted in four patients (one renal artery dissection, and three femoral pseudoaneurysms).

As compared with baseline, there was a significant reduction in SBP and DBP at 12 months (25 and 11 mm, p < 0.0001), which was noted as early as 1 month (20 and 10 mm, p < 0.0001), and sustained throughout follow-up. At 2 years (n = 105), BP was reduced by 32/14 mm Hg in the treatment arm (p < 0.001). At 3 years, follow-up data were available for 88 patients. BP was reduced by 32/14 mm Hg in the treatment arm (p < 0.001). The overall response rate was 80% (defined as ≥10 mm decrease in SBP) at 1 year, 82% at 2 years, and 93% at 3 years. There was no change in heart rate over the 3 years of follow-up. There was no change in Na or K levels over time, but estimated glomerular filtration rate declined from 85.2 ml/min at baseline to 74.3 ml/min at 3 years; there appeared to be a gradual decline over time. Four cases of renal artery stenosis were noted.

Interpretation:

The results of this first-in-man (Phase II) trial indicate that RF ablation resulting in renal sympathetic denervation results in a significant reduction in SBP and DBP at 12 months. This response appeared to be robust up to 3 years of follow-up, although no control group was present. Further long-term data and randomized controlled trials are necessary. Surgical sympathectomy has been known for a long time, but is currently reserved for only the most intractable hypertension. Even if this technique proves to be effective, it is thus unknown how widely acceptable this technique will be.

References:

Presented by Dr. Henry Krum at the European Society of Cardiology Congress, Amsterdam, Holland, September 3, 2013.

Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011 May;57(5):911-7.

Presented by Dr. Henry Krum at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, CA, September 25, 2009.

Keywords: Aneurysm, False, Follow-Up Studies, Renal Artery Obstruction, Sympathetic Nervous System, Sympathectomy, Glomerular Filtration Rate, Heart Rate, Hypertension, Systole


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