Summary
The Renal Denervation in Patients With Uncontrolled Hypertension trial [SYMPLICITY HTN-3; NCT01418261] was the first randomized, blinded, sham-controlled clinical trial of renal denervation for treatment-resistant hypertension. In addition to the blinding and sham control, post hoc analyses have identified potential factors that may account for the negative results, including the patient population and procedural variability, which are discussed in this 12-month post hoc analysis.
- Hypertensive Disease
- Interventional Techniques & Devices
- Cardiology Clinical Trials
- Hypertensive Disease
- Interventional Techniques & Devices
- Cardiology Clinical Trials
- Cardiology
The Renal Denervation in Patients With Uncontrolled Hypertension trial [SYMPLICITY HTN-3; NCT01418261] was the first randomized, blinded, sham-controlled clinical trial of renal denervation for treatment-resistant hypertension. The 6-month results confirmed the safety of renal denervation but the primary efficacy end point was not met [Bhatt DL et al. N Engl J Med. 2014]. In addition to the blinding and sham control, post hoc analyses have identified potential factors that may account for the negative results, including the patient population and procedural variability. Deepak L. Bhatt, MD, MPH, Brigham and Women's Hospital, Boston, Massachusetts, USA, presented the 12-month post hoc analysis of the SYMPLICITY HTN-3 trial.
After 2 screening visits, potential subjects with refractory hypertension underwent renal angiogram and eligible patients were randomized to renal denervation (n = 364) or a sham procedure (n = 171) [Bhatt DL et al. N Engl J Med. 2014]. Medication changes were not permitted for 6 months. The primary efficacy end point of office systolic BP (SBP) at 6 months was significantly reduced from baseline in the denervation (n = 353; P < .001) and sham (n = 171; P < .001) groups but was not significantly different between the 2 groups (P = .26).
All clinicians and patients were unblinded to randomization after the 6-month evaluation. Sham control patients were permitted to crossover to renal denervation following the 6-month primary assessment if they continued to meet the study inclusion criteria. Study follow-up will continue for up to 5 years.
A total of 322 patients (91%) in the denervation group completed the 12-month postdenervation follow-up. Among the sham patients, 101 crossed over to renal denervation; of these, 93 (96.9%) completed the 12-month postdenervation follow-up. A total of 48 sham patients (77%) completed the 12-month follow-up.
SBP and diastolic BP (DBP) reductions from baseline in the denervation group were −15.3 and −6.6 mm Hg, respectively, at 6 months (P < .001) and −18.9 and −7.8 mm Hg (P < .001), respectively, at 12 months. SBP and DBP reductions from baseline in the crossover group at 6 months were −17.7 and −7.1 mm Hg, respectively. In matched denervation patients (n = 319), the changes in office SBP and DBP at 6 months were −15.5 and −6.6 mm Hg, respectively, and −18.9 and −7.8 mm Hg, respectively, at 12 months (P = .025 for SBP difference; Figure 1).
Change in Office BP at 6 and 12 Months for Matched Denervation Patients
BP, blood pressure; DBP, diastolic blood pressure; RDN, renal denervation; SBP, systolic blood pressure; SE, standard error.
BP changes are vs patient baseline, not RDN vs Control. Error bars = 1.96 SE.
Reproduced with permission from DL Bhatt, MD.
SBP and DBP reductions from baseline in the non-crossover sham group were 32.9 and 13.3 mm Hg, respectively, at 6 months (P < .001) and 21.4 and 8.2 mm Hg, respectively, at 12 months (P < .001; Figure 2).
Change in Office BP at 6 and 12 Months for Noncrossover Sham Patients
BP, blood pressure; DBP, diastolic blood pressure; RDN, renal denervation; SBP, systolic blood pressure; SE, standard error.
BP changes are vs patient baseline, not RDN vs Control. Error bars = 1.96 SE.
Reproduced with permission from DL Bhatt, MD.
Figure 3 shows the relationship between office SBP changes and number of ablations attempted for combined denervation patients at 6 months.
SBP Changes and No. of Ablations Attempted at 6 Months
SBP, systolic blood pressure.
Denervation and crossover subjects combined.
Reproduced with permission from DL Bhatt, MD.
The 12-month results of the SYMPLICITY HTN-3 trial are consistent with the previously reported 6-month findings. The safety of renal sympathetic denervation was maintained, but BP reductions were similar to those in patients receiving the sham procedure. The positive correlation of the total number of ablations and the circumferential pattern of ablations on systolic BP reduction was maintained and enhanced with the addition of the 6-month crossover subject data. These post hoc observations suggest hypotheses related to optimization of the denervation procedure that may inform the design of future renal denervation trials.
- © 2014 MD Conference Express®
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