Radiofrequency Renal Denervation for Uncontrolled Hypertension: A Sham-Controlled Meta-Analysis

Introduction/Background: Uncontrolled hypertension remains a major modifiable cause of cardiovascular and renal disease. Catheter-based renal denervation may lower blood pressure by reducing renal sympathetic activity, but sham-controlled evidence is needed. Research Question/Hypothesis: This meta-analysis evaluated whether radiofrequency renal denervation reduces ambulatory and office blood pressure compared with sham control in adults with uncontrolled hypertension. Methods/Approach: We performed a systematic review and meta-analysis of randomized sham-controlled trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidance. PubMed/MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, reference lists, and relevant reviews were searched. Eligible studies enrolled adults with uncontrolled hypertension and compared contemporary radiofrequency renal denervation with a sham procedure. The primary outcome was change in 24-hour ambulatory systolic blood pressure. Secondary outcomes included office systolic blood pressure, ambulatory and office diastolic blood pressure, escape criteria, and short-term safety. Mean differences (MDs) and risk ratios (RRs) were pooled using random-effects models. Results/Data: Three multicenter randomized sham-controlled trials including 491 participants were included. Townsend et al. and Böhm et al. evaluated patients not receiving antihypertensive medications, whereas Kandzari et al. enrolled patients receiving 1 to 3 antihypertensive drugs. All trials used the Symplicity Spyral system; follow-up ranged from 3 to 6 months. Renal denervation reduced 24-hour ambulatory systolic blood pressure versus sham control (MD -4.50 mmHg, 95% CI -6.60 to -2.41; p<0.0001; I 2 =0%). Office systolic blood pressure was also lower with renal denervation (MD -6.74 mmHg, 95% CI -9.45 to -4.02; p<0.00001; I 2 =0%). Reductions favored renal denervation for 24-hour ambulatory diastolic blood pressure (MD -3.45 mmHg, 95% CI -4.67 to -2.24; p<0.00001; I 2 =0%) and office diastolic blood pressure (MD -4.33 mmHg, 95% CI -5.79 to -2.87; p<0.00001; I 2 =0%). Escape criteria were met by 20 of 242 renal denervation patients and 35 of 249 sham-control patients (RR 0.58, 95% CI 0.35 to 0.97; p=0.04; I 2 =0%). Adverse events were rare or absent, with no major device-related or procedure-related safety signal. Conclusion(s): In randomized sham-controlled trials of adults with uncontrolled hypertension, radiofrequency renal denervation was associated with consistent reductions in ambulatory and office blood pressure and fewer escape-criteria events compared with sham control. Safety findings were reassuring, but limited trial numbers and follow-up preclude conclusions about rare events or long-term cardiovascular outcomes.