Renal denervation in 2025: long-term evidence supporting sympathetic modulation as a durable strategy for uncontrolled hypertension

Background: Renal denervation (RDN) has emerged as a promising device-based therapy for uncontrolled hypertension. Recent data from major cardiovascular conferences (EuroPCR, ESH, TCT 2025) provide unprecedented 3-year follow-up evidence on efficacy, safety, and clinical outcomes. Methods: We synthesize key findings from the SPYRAL HTN-ON MED 3-year final report, the Global Symplicity Registry DEFINE (GSR-DEFINE) real-world data, SPYRAL AFFIRM post-approval study, and pooled analyses on acute hypertensive events. Data sources are distiguisehed by level of evidence: randomized sham-controlled trials versus observational registry data. Results: At 3 years, SPYRAL HTN-ON MED demonstrated sustained office systolic blood pressure (SBP) reductions of -18.5 mmHg (RDN) versus -11.7 mmHg (sham), with treatment difference of -6.8 mmHg (p = 0.0002). The GSR-DEFINE registry (n = 3109) showed -20.5 mmHg office SBP reduction at 3 years with progressively increasing effect over time. Pooled analysis revealed a 43% reduction in acute hypertensive events with RDN. No renal artery stenosis or need for reintervention was observed through 3 years. Conclusion: These data support RDN as a potentially durable and safe adjunctive therapy for uncontrolled hypertension in appropriately selected patients. Benefits appear to extend to high-risk populations including patients with diabetes, chronic kidney disease, and prior stroke, though long-term cardiovascular outcome data remain awaited.