Abstract Body: Background:
Resistant hypertension (RH)—defined as uncontrolled blood pressure (BP) despite adherence to three or more antihypertensive medications—remains a major contributor to cardiovascular risk. Over the past decade, catheter-based renal denervation (RDN) has evolved with improvements in ablation techniques and patient selection. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of RDN in patients with RH.

Methods:
We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) published from January 2010 to March 2025 that compared RDN to standard or optimized medical therapy. Two reviewers independently screened studies, extracted data and assessed risk of bias. A random-effects meta-analysis was performed. Primary outcomes were change in office and 24-hour ambulatory systolic BP. Secondary outcomes included major adverse cardiovascular events (MACE), renal function (eGFR), antihypertensive medication burden, and procedural safety. Heterogeneity was assessed and sensitivity analyses were conducted based on device type and follow-up duration.

Results:
18 RCTs enrolling a total of 4,215 patients met inclusion criteria. RDN significantly reduced office systolic BP (mean difference [MD]: -9.2 mmHg; 95% CI: -11.0 to -7.4; I2=57%; p<0.001) and 24-hour ambulatory systolic BP (MD: -7.1 mmHg; 95% CI: -8.3 to -5.9; I2=48%; p<0.001). A 25% relative reduction in MACE was observed with RDN compared to control (risk ratio [RR]: 0.75; 95% CI: 0.62–0.90; p=0.003; I2=21%). RDN also led to a notable reduction in medication burden (MD: -1.4 antihypertensives; 95% CI: -1.9 to -0.9; p<0.001). No significant differences were seen in procedural complications (RR: 1.03; 95% CI: 0.86–1.22; p=0.74) or decline in eGFR (MD: -0.6 mL/min/1.73 m2; 95% CI: -1.4 to +0.2; p=0.13). Among trials with ≥12 months follow-up, BP-lowering effects were sustained over time.

Conclusions:
RDN appears to be a safe and effective adjunct for lowering BP in patients with resistant hypertension. It is associated with meaningful reductions in systolic BP, fewer cardiovascular events, and a reduced need for antihypertensive medications, without compromising renal function or procedural safety. Ongoing large-scale studies are warranted to determine long-term benefits, cost-effectiveness, and real-world applicability.

Keywords:
Renal denervation, resistant hypertension, randomized controlled trials