Radiofrequency renal denervation (RDN) did not significantly reduce blood pressure (BP) at 6 months compared to a sham procedure in patients on antihypertensive medications, new study results show.
David E. Kandzari, MD, of the Piedmont Heart Institute Atlanta, presented these findings Monday at the American Heart Association Scientific Sessions 2022 in Chicago.
Uncontrolled hypertension is common and is associated with adverse cardiovascular events. Prior data suggest that a 5-mmHg absolute reduction in office systolic BP leads to a 10% reduction in major cardiovascular events. RDN may reduce BP by targeting the sympathetic nervous system.
The SPYRAL HTN-OFF MED pivotal and SPYRAL HTN-ON MED pilot trials demonstrated significant and clinically relevant BP lowering after radiofrequency RDN in the absence and presence of antihypertensive medications. The effect of RDN was further explored in the SPYRAL HTN-ON MED trial by comparing RDN with Medtronic’s Symplicity Spyral Multi-electrode Renal Denervation System to a sham procedure.
The SPYRAL HTN-ON MED trial included patients with systolic blood pressure (SBP) ≥150 to 180 mmHg that was stable on up to three antihypertensive medications for at least 6 weeks. The primary efficacy endpoint was change in 24-hour systolic ambulatory blood pressure monitoring (ABPM) at 6 months, and the primary safety endpoint was major adverse events (MAE) at 1 month in the pooled SPYRAL HTN-ON MED and SPYRAL HTN-OFF MED study populations compared to a prespecified 7.1% performance goal.
The SPYRAL HTN-ON MED pilot study randomized 80 patients, while the SPYRAL HTN-ON MED expansion cohort randomized 257 patients. Of these 337 patients, 206 patients were randomized to the RDN arm and 131 to the sham-control arm. Their mean age was 55 years old, they were predominantly male (RDN 81.1%, sham control 78.6%), and a minority were Black (RDN 17%, sham control 19.1%). Baseline 24-hour systolic ABPM was similar between the groups (RDN 149.6 ± 7.0 mmHg vs. control 149.3 ± 7.0 mmHg), the and number of antihypertensive medications at baseline was similar (1.9 ± 0.8 in both arms). In the RDN arm, 99.5% of procedures were successful, with a mean of 2.3 ± 0.6 main renal arteries treated.
The primary efficacy endpoint, change in 24-hour systolic ABPM was not different between RDN (-6.5 mmHg) and control (-4.5 mmHg) 24-hour systolic ABPM: vs. (absolute difference: -1.9 mmHg, p=0.12).
The primary safety endpoint was met, with a mean MAE rate of 0.4% (upper one-sided 95% confidence interval: 1.9%; performance goal: 7.1%; p<0.0013) at 1 month in the pooled SPYRAL HTN-ON MED and OFF MED study populations. There was one MAE, a vascular complication requiring treatment, accounting for the 0.4% rate.
Looking at 6-month safety results in the pilot and expansion SPYRAL HTN-ON MED trials, there were two MAEs (both vascular complications requiring intervention) for a 1% rate in the RDN arm and two MAEs (one vascular complication requiring intervention and one new stroke) for a 1.6% rate in the control arm.
At 6 months, the number of antihypertensives used in each group was not different, but “medication burden,” based on number, class and dose of medication, was higher in the control group compared to RDN (3.5 vs. 2.9, p=0.04). There was no significant difference in adverse events between groups at 6 months.
Kandzari posited that results of the trial may have been altered by enrollment during the COVID-19 pandemic, which may be associated with lifestyle changes and, therefore, BP modulation. Disproportionate medication changes in the control arm compared to the RDN arm may have also predisposed the trial to a null result, Kandzari said.
The SPYRAL HTN trials are sponsored by Medtronic Vascular.
Note: This article has been updated to clarify that the primary safety endpoint was based on a pooled analysis of the SPYRAL HTN-ON MED and OFF MED trials and that the primary efficacy endpoint was based on a combination of the SPYRAL HTN-ON MED pilot trial and expansion cohort.