Long-Term Safety and Efficacy of Renal Denervation: 24-Month Results From the SPYRAL HTN-ON MED Trial

BACKGROUND: Six-month results from the SPYRAL HTN-ON MED trial (SPYRAL HTN-ON MED Study of Renal Denervation With the Symplicity Spyral Multi-Electrode Renal Denervation System) demonstrated that renal denervation (RDN) reduced office blood pressure (BP), and not 24-hour ambulatory systolic BP, compared with sham control in hypertensive patients. In this prespecified analysis of the ON MED trial, long-term changes in BP, antihypertensive drug use, and safety outcomes through 24 months are compared between RDN and sham control groups. METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, blinded trial enrolling 337 patients globally from 56 clinical centers. Eligible patients had an office systolic BP of 150 to 180 mm Hg, a diastolic BP ≥90 mm Hg, and a 24-hour ambulatory systolic BP of 140 to 170 mm Hg. Patients were randomized to RDN or a sham control procedure and were prescribed a stable regimen of 1 to 3 antihypertensive medications through 6 months. After 6 months, patients and physicians were unblinded with permitted changes to antihypertensive therapy, and control patients were permitted to cross over. Crossover patients had their last observations carried forward as part of the control group. Statistical analyses were conducted on the population as randomized. RESULTS: At 24 months, the RDN group experienced significantly greater mean reductions in ambulatory systolic BP (−12.1±15.3 mm Hg [n=176] versus −7.0±13.1 mm Hg [n=33]; difference: −5.7 mm Hg; P =0.039) and office systolic BP (−17.4±16.1 mm Hg [n=187] versus −9.0±19.4 mm Hg [n=35]; difference: −8.7 mm Hg; P =0.0034) compared with sham controls. At 24 months, antihypertensive medications increased significantly more in the sham group (1.7 versus 2.7) compared with the RDN group (1.8 versus 2.4; P =0.046). Sensitivity analyses accounting for missing sham patient BP values due to crossover yielded consistent results in favor of RDN for 24-hour ambulatory ( P =0.023) and office systolic BP ( P <0.0001). Clinically adverse events were rare, with no instances of renal artery stenosis through 24 months. CONCLUSIONS: RDN produced significantly greater ambulatory and office systolic BP reductions at 24 months compared with sham control, despite higher antihypertensive medication use in the control group. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02439775.