Renal Denervation: New Evidence Supporting Long-Term Efficacy, Alternative Access Routes, and Cost-Effectiveness

Abstract

The treatment landscape for uncontrolled and resistant hypertension continues to evolve, with renal denervation (RDN) emerging as an increasingly validated third pillar of therapeutic options, in addition to lifestyle modification and pharmacological therapy [1, 2]. Three recent studies published in this issue provide important new insights into the long-term efficacy, procedural innovations, and economic value of RDN, while highlighting areas requiring further investigation.

Brouwers et al. provide valuable 10-year follow-up data on RDN in real-world practice, demonstrating sustained blood pressure reductions and favorable safety outcomes [3]. Their findings show significant reductions in both office (approximately 20 mm Hg) and ambulatory (approximately 15 mm Hg) systolic blood pressure measurements maintained up to 10 years post-procedure, without significant changes in antihypertensive medication numbers. The study highlights an important evolution in RDN technology—the transition from first to second-generation devices. The authors found that controlled blood pressure at 1 year was more frequently achieved with the second-generation device (78% vs. 13%), associated with more ablation spots, including branch renal artery ablation [3]. This finding lends evidence that technological improvements and more comprehensive denervation approaches may enhance therapeutic success.

Zuo et al. introduce an important procedural innovation by demonstrating the feasibility and comparable efficacy of upper extremity access (UEA)—either transradial or transbrachial—compared to traditional transfemoral access (TFA) for RDN [4]. This alternative approach addresses TFA's limitation in accessing renal arteries in patients with unfavorable vascular anatomy. About 30% of patients had vascular morphology better suited to UEA, highlighting this technical advance's clinical relevance.

Kario et al. provide the first comprehensive cost-effectiveness analysis of RDN in an Asian healthcare setting [5]. Their finding that RDN is cost-effective in the Japanese healthcare system, with an incremental cost-effectiveness ratio well below the willingness-to-pay threshold, adds important economic validation to the growing clinical evidence.

Each study reveals important limitations that should inform future research. The long-term follow-up data's relatively small sample size and single-center experience may limit broader generalizability. Selection bias may explain why patients treated with second-generation devices showed better early hypertension control, yet systolic blood pressure reductions at 5–10 years (from first-generation devices) were similar to those at 2–4 years (from both generations) [3].

Although Zuo's investigation of alternative access routes represents an important technical advance, the retrospective design and non-randomized allocation introduce potential selection bias. The 6F renal double curve guide catheter [6], compatible with second-generation devices, can access renal arteries with acute inferior take-off angles via TFA. According to our experience, RDN could be performed successfully via TFA in more than 98% of cases.

The cost-effectiveness analysis makes a significant contribution but relies on model-based projections and assumptions about long-term durability, highlighting the need for ongoing economic evaluation as more data becomes available [7].

Several critical areas require further investigation. Given blood pressure-lowering response rates of 65%–90% in randomized trials [8-10], patient selection remains challenging without reliable success predictors [11]. The impact of vascular anatomy on procedure planning and baseline characteristics on outcomes needs better characterization.

Procedural optimization represents another crucial area. Current ablation protocols vary significantly, and questions remain about optimal ablation spots [11]. Real-time assessment of denervation effectiveness is under investigation [12], though remaining elusive, and the role of imaging in procedure guidance needs further definition [13]. Device technology continues to evolve, but purpose-built devices for different access routes and integration of sensing/stimulation capabilities could further enhance procedural success.

The impact of RDN on cardiovascular endpoints needs better characterization, particularly in specific populations. Night-time blood pressure control has emerged as an interesting aspect of RDN therapy [14], requiring a better understanding of mechanisms and outcome measures optimization.

Healthcare system integration presents practical challenges requiring attention to implementation strategies, training requirements, quality metrics, and resource utilization optimization across different settings [15].

These studies make important contributions to understanding RDN in treating uncontrolled and resistant hypertension [3-5]. The demonstration of sustained efficacy, procedural innovations, and economic value strengthens RDN's position as a therapeutic option. However, questions remain regarding patient selection, procedural optimization, and long-term outcomes. Addressing these needs through focused research (Table 1) will be crucial for optimizing this promising therapy.