Final 3-year report of the Symplicity HTN-1 study is published online in the Lancet

The Symplicity HTN-1 (n=150) was the first multicenter, proof-of-concept and safety study for patients with resistant arterial hypertension (mean age 57 years) undergoing catheter-based renal denervation. Patients in the Symplicity HTN-1 study were heavily medicated, taking an average of five antihypertensive drugs, and were still poorly controlled (office blood pressure 175/98mmHg). The primary endpoint was peri-procedural and safety of the treatment (n=45) after 1 and 12 month published in 2009 at the Lancet (1). After four weeks, a significant reduction of systolic and diastolic office blood pressure by 14 and 10mmHg has been described, which increased to 27 and 17mmHg (p=0.026) after 12 months (1). The recently presented 36 months long-term follow-up indicates a sustained blood pressure lowering effect of 32 and 14mmHg (p<0.01, n=88), making a significant functional regrowth or re-innervation of the kidneys unlikely. A drop of 10mmHg and more in systolic blood pressure (response to treatment) were seen in 93% at the final report after 3 years. One new renal artery stenosis requiring stenting and three deaths unrelated to renal denervation occurred during the 3 years of follow-up.

(1) Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof-of-principle cohort study. Lancet 2009;373:1275-81.

Sebastian Ewen

Abstract

Background

Renal denervation (RDN) with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension. We assessed the long-term antihypertensive effects and safety.

Methods

Symplicity HTN-1 is an open-label study that enrolled 153 patients, of whom 111 consented to follow-up for 36 months. Eligible patients had a systolic blood pressure of at least 160 mm Hg and were taking at least three antihypertensive drugs, including a diuretic, at the optimum doses. Changes in office systolic blood pressure and safety were assessed every 6 months and reported every 12 months. This study is registered with ClinicalTrials.gov, numbers NCT00483808, NCT00664638, and NCT00753285.

Findings

88 patients had complete data at 36 months. At baseline the mean age was 57 (SD 11) years, 37 (42%) patients were women, 25 (28%) had type 2 diabetes mellitus, the mean estimated glomerular filtration rate was 85 (SD 19) mL/min per 1·73 m2, and mean blood pressure was 175/98 (SD 16/14) mm Hg. At 36 months significant changes were seen in systolic (−32·0 mm Hg, 95% CI −35·7 to −28·2) and diastolic blood pressure (−14·4 mm Hg, −16·9 to −11·9). Drops of 10 mm Hg or more in systolic blood pressure were seen in 69% of patients at 1 month, 81% at 6 months, 85% at 12 months, 83% at 24 months, and 93% at 36 months. One new renal artery stenosis requiring stenting and three deaths unrelated to RDN occurred during follow-up.

Interpretation

Changes in blood pressure after RDN persist long term in patients with treatment-resistant hypertension, with good safety.

Funding

Ardian LLC/Medtronic Inc.