Nassar, Mostafa

Background: Resistant hypertension (RH), defined as uncontrolled blood pressure (BP) despite ≥3 antihypertensive agents at maximally tolerated doses, remains a significant therapeutic challenge. Device-based renal denervation (RDN), using either radiofrequency (RF) or ultrasound (US) ablation, has shown promise in reducing BP. While both methods have demonstrated efficacy versus sham controls in randomized controlled trials (RCTs), direct comparisons remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of RF- and US-based RDN in patients with resistant hypertension. Methods: Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through April 2025 for RCTs comparing RDN versus sham in RH. Eligible trials reported systolic or diastolic BP outcomes via ambulatory, office, or home measurements. Pooled mean differences (MD) and risk ratios (RR) were calculated using a random-effects model. Subgroup analyses were conducted by RDN modality and follow-up duration. Results: Seventeen RCTs met inclusion criteria. RDN significantly reduced ambulatory systolic BP (MD: −3.14 mmHg; 95% CI: −5.30 to −0.98; p=0.004) and diastolic BP (MD: −1.40 mmHg; 95% CI: −2.45 to −0.35; p=0.009) compared to sham. RF-based RDN showed consistent statistically significant reductions in both SBP and DBP across ambulatory and in-office measurements. In contrast, US-based RDN demonstrated variable efficacy, with only daytime DBP showing a marginal benefit (MD: −1.32 mmHg; p=0.04). Safety outcomes, including mortality, acute kidney injury, hypertensive crisis, and hypotension, were similar between groups. Conclusion: RDN offers a significant BP-lowering effect in resistant hypertension, with RF-based RDN yielding more consistent benefits across diverse measurement settings. US-based RDN showed limited but promising effects. Both techniques demonstrated acceptable safety profiles. Further head-to-head trials are needed to confirm long-term comparative effectiveness.