Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension - SYMPLICITY HTN-2

Jun 08, 2014
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Ardian
Date Presented:
01/01/2010
Date Updated:
06/08/2014
Original Posted Date:
06/08/2014
References

Description:

The goal of the trial was to compare a strategy of renal sympathetic denervation with standard therapy among patients with treatment-resistant hypertension.

Hypothesis:

Renal sympathetic denervation will improve blood pressure control.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • 18-85 years of age
  • Systolic blood pressure >160 mm Hg (>150 mm Hg for diabetics) despite the use of three or more antihypertensive medications

    Number of screened applicants: 190
    Number of enrollees: 106
    Duration of follow-up: 36 months
    Mean patient age: 58 years
    Percentage female: 35%

Exclusions:

  • eGFR <45 ml/min/1.73 m2
  • Type 1 diabetes
  • Contraindication to magnetic resonance imaging
  • Stenotic valvular heart disease
  • Pregnancy
  • History of myocardial infarction, unstable angina, or cerebrovascular accident in the previous 6 months
  • Renal artery stenosis, previous renal artery revascularization, or renal artery <4 mm diameter or <20 mm length

Primary Endpoints:

  • Change in systolic blood pressure at 6 months

Secondary Endpoints:

  • Acute procedural safety
  • Chronic procedural safety defined as a reduction in eGFR >25% or a new renal stenosis >60%
  • Composite of sudden death, death from heart failure, death from aortic or peripheral arterial disease, death from renal failure, myocardial infarction, heart failure, stroke, aortic or lower extremity revascularization procedure, lower limb amputation, dialysis, hospital admission for hypertensive crisis, or hospital admission for atrial fibrillation

Drug/Procedures Used:

Patients with treatment-resistant hypertension were randomized to renal sympathetic denervation (n = 52) versus standard medical therapy (n = 54).

Renal sympathetic denervation was performed with the Symplicity Catheter System, which delivers radiofrequency low-energy along both renal arteries.

In both groups, changes to baseline antihypertensive medication doses were not allowed unless deemed medically necessary. Antihypertensive agents could be added or withdrawn according to physician discretion.

Principal Findings:

Overall, 106 patients were randomized. There was no difference in baseline characteristics between the study groups except for estimated glomerular filtration rate (eGFR). In the renal denervation group, the mean age was 58 years, 35% were women, mean blood pressure was 178/97 mm Hg, and mean number of antihypertensive medications was 5.2. Mean eGFR was 77 ml/min/1.73 m2 in the denervation group versus 86 ml/min/1.73 m2 in the control goup. There were no serious device complications.

The renal denervation group experienced a 32/12 mm Hg reduction in blood pressure versus 1/0 mm Hg increase in the control group. The between-group difference in blood pressure at 6 months was 33/11 mm Hg (p < 0.0001).

The proportion of patients who experienced at least a 10 mm Hg drop in systolic blood pressure was 84% in the denervation group versus 35% in the control group (p < 0.0001). The proportion of patients who had drug reductions was 20% in the denervation group versus 6% in the control group (p < 0.04). Renal function was unchanged in both groups at follow-up.

At 6 months, 35 patients in the control group were allowed to crossover and have renal denervation. At 12 months, the renal denervation group had a 28/10 mm Hg reduction in blood pressure versus 24/8 mm Hg reduction in the control group that subsequently underwent denervation. At 30 months, among all patients who received renal denervation, the mean change in blood pressure was 34/13 mm Hg compared with baseline.

Between 12 and 36 months, there were five hypertensive events that required hospitalization, two cases of acute renal failure (one due to dehydration and one due to interstitial nephritis), and three deaths (one was due to cardiogenic shock after aortic valve replacement surgery and in two cases, the cause was unknown).

Interpretation:

Among patients with treatment-resistant hypertension, renal sympathetic denervation appears to be effective and safe. The patients enrolled in this study had uncontrolled hypertension (mean 178/97 mm Hg) despite being on more than five antihypertensive drugs.

At this time, results do not apply to patients with mild to moderate hypertension. Since renal nerves may theoretically re-grow, long-term follow-up of renal sympathetic denervation is needed; however, no significant safety concerns were observed to 36 months. Although renal denervation appeared to be effective in this trial, the SYMPLICITY HTN-3 trial failed to document a benefit from renal denervation compared with sham control at 6 months.

References:

Esler MD, Böhm M, Sievert H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J 2014;Jun 4:[Epub ahead of print].

Esler MD, Krum H, Schlaich M, Schmieder RE, Böhm M, Sobotka PA, on behalf of the Symplicity HTN-2 Investigators. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial. Circulation 2012;126:2976-82.

Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010;376:1903-9.

Presented by Dr. Murray Esler at the American Heart Association Scientific Sessions, Chicago, IL, November 17, 2010.

Keywords: Follow-Up Studies, Denervation, Acute Kidney Injury, Blood Pressure, Dehydration, Shock, Cardiogenic, Renal Artery, Sympathectomy, Nephritis, Interstitial, Glomerular Filtration Rate, Diabetes Mellitus, Hypertension


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