Catheter-based renal denervation (RDN) could lower blood pressure (BP) in patients with resistant hypertension over 3 years, said researchers, who presented their findings on Sunday at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 conference in Boston.
The researchers of the Medtronic-sponsored study described the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial as “adding to the totality of evidence” that supports the safety of RDN to 36 months after the procedure.
“From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive RDN had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control,” said the study, which was published simultaneously online in The Lancet.
Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center Harvard Medical School, Boston, added in a press release announcing the results, “Long-term follow-up from the SYMPLICITY HTN-3 trial showed that renal denervation is safe, and no late-emerging complications were found.
“In addition, significant reductions were seen in office and 24-hour blood pressure after three years, independent of medications.
“These findings indicate that durable blood pressure reductions with radio-frequency renal denervation in combination with maximal medical therapy can be safely achieved.”
These data support the growing body of evidence of favorable, durable and safe long-term results of RDN, in the presence of maximal medical therapy, with the potential for larger reductions in BP with longer durations of follow-up, Bhatt said during a press conference.
The catheter-based approach could also benefit patients with treatment-resistant hypertension or those who prefer to reduce pill burden or have suboptimal medication adherence in BP management.
SYMPLICITY HTN-3 study approach
The SYMPLICITY HTN-3 study design, 6- and 12-month outcomes, have been previously reported, with the latest 36-month follow-up results presented at TCT 2022.
Briefly, the study was a single-blind, multicenter, sham-controlled, randomized clinical trial, conducted in 88 sites across the U.S.
Adults aged 18–80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, were enrolled.
These individuals recorded a seated office systolic BP of 160 mm Hg or more and 24-hour ambulatory systolic BP of 135 mm Hg or more.
A total of 535 patients were then randomized 2:1 to RDN using the Symplicity Flex catheter (n=364) or sham control (n=171).
Unblinding occurred after 6 months, and eligible control patients could cross over to RDN. For the 101 patients who crossed over and received RDN, their most recent blinded pre-crossover BP measurement and medication data were used as controls. Treatment differences were adjusted for baseline BP.
The primary efficacy endpoint of the original study was the change in office systolic blood pressure (OSBP) from baseline to 6 months for the RDN group compared with the sham control.
The main outcome of the current study was the comparison of changes in blood pressure between the renal artery denervation group and the sham control group at 36 months.
6, 12 and 36-month findings
At 6 months, RDN was found to be safe but did not show any significant incremental blood pressure lowering benefit compared with a sham procedure.
At 12 months, RDN patients had significantly greater OSBP reductions compared with sham control after crossover imputation (-18.9 mmHg vs -6.3 mmHg, p<0.0001, respectively).
In addition, the number of antihypertensive drugs was similar between patients in the RDN and control groups (4.7±1.4 vs. 4.7±0.9, p=0.22).
The OSBP reductions continued each year following the procedure, and at 36 months, the reduction in BP following RDN was -26.4 mmHg (standard deviation (SD) 25.9) compared with -5.7 mmHg (SD 24.4) for the control group (adjusted treatment difference –22·1 mm Hg; 95% confidence interval [CI] –27·2 to –17·0; p≤0·0001).
Similar results were observed in other measures of blood pressure (office diastolic BP, 24-hour diastolic BP).
The change in 24-hour ambulatory systolic BP at 36 months was –15·6 mm Hg (standard deviation 20.8) in the renal artery denervation group and –0.3 mm Hg (15.1) in the sham-control group (adjusted treatment difference –16.5 mm Hg; 95% CI –20.5 to –12.5; p≤0.0001).
Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from RDN.
Researchers also compared the SYMPLICITY HTN-3 results to the SPYRAL HTN-ON MED trial results, where the SYMPLICTY HTN-3 trial used a first-generation catheter with one electrode that only treated the main renal artery.
SPYRAL HTN-ON MED utilized a second-generation catheter with four electrodes which circumferentially treated the main renal artery and branches.
The mean number of ablations for SPYRAL HTN-ON MED was 45.9 ±13.7 compared with 11.2±2.8 for SYMPLICITY HTN-3.
A comparison of BP in RDN patients between the two trials shows that patients in SPYRAL HTN-ON MED had similar long-term BP reductions through 3 years [OSBP: -28.5 mm Hg versus -25.2 mmHg (p=0.50) and 24 Hour SBP: -22.1 mmHg versus -15, mmHg (p=0.06)].
“In this final follow-up from the randomized SYMPLICITY HTN-3 trial, we show significant reductions in office and 24-hour ambulatory systolic and diastolic, night-time, morning, and daytime blood pressure, with no signal of late-emerging complications from RDN,” the research team concluded.
“This is the longest safety analysis of the RDN procedure in a randomized trial setting and highlights the procedure’s overall safety.
“These findings add to the growing body of evidence supporting the reductions in blood pressure that are safely achievable with catheter-based renal artery denervation and suggest that the clinical effect of renal artery denervation does not wane over time but might increase.”
Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet 2022 Sep 18 (Article in press).
Image Credit: Jason Wermers/CRTonline.org