Renal Denervation for Resistant Hypertension: A Meta-Analysis of Sham-Controlled Trials

Introduction/Background: Resistant and uncontrolled hypertension remain major drivers of cardiovascular morbidity despite multidrug pharmacotherapy, lifestyle intervention, and recognition of nonadherence and therapeutic inertia. Catheter-based renal denervation (RDN) has re-emerged after sham-controlled trials, but its blood pressure effect and safety profile require precise quantification. Research Questions/Hypothesis: We hypothesized that RDN reduces ambulatory and office blood pressure compared with sham control without increasing renal or procedural safety events. Methods/Approach: Randomized, sham-controlled adult trials of catheter-based RDN for hypertension were synthesized. Eligible trials evaluated first- or second-generation radiofrequency, ultrasound, or alcohol-mediated RDN in patients treated with or without antihypertensive medications. Outcomes included 24-hour and office systolic blood pressure (SBP), 24-hour and office diastolic blood pressure (DBP), medication-status interaction, vascular complications, renal artery stenosis >70%, hypertensive crisis, all-cause death, and estimated glomerular filtration rate. Summary data were pooled using study-level, pairwise, random-effects meta-analysis. Results/Data: A total of 10 trials comprising 2,478 participants were included. Compared with sham control, RDN reduced 24-hour SBP (mean difference [MD], -4.4 mm Hg; 95% CI, -6.1 to -2.7; P<0.00001) and office SBP (MD, -6.6 mm Hg; 95% CI, -9.7 to -3.6; P<0.0001). RDN also reduced 24-hour DBP (MD, -2.6 mm Hg; 95% CI, -3.6 to -1.5; P<0.00001) and office DBP (MD, -3.5 mm Hg; 95% CI, -5.4 to -1.6; P=0.0003). SBP effects did not differ significantly between trials performed with versus without concomitant antihypertensive medications for 24-hour SBP (P for interaction=0.62) or office SBP (P for interaction=0.73). RDN did not significantly increase vascular complications (OR, 1.69; 95% CI, 0.57 to 5.00; P=0.34), renal artery stenosis >70% (OR, 1.50; 95% CI, 0.06 to 36.97; P=0.80), hypertensive crisis (OR, 0.65; 95% CI, 0.30 to 1.38; P=0.26), or all-cause death (OR, 1.76; 95% CI, 0.34 to 9.20; P=0.50). Change in estimated glomerular filtration rate was comparable between groups (P for interaction=0.84). Conclusion(s): In sham-controlled randomized evidence, RDN produces statistically significant but modest reductions in ambulatory and office blood pressure without a significant short-term safety penalty. RDN should be considered an adjunctive option for carefully selected patients after confirmation of true uncontrolled hypertension, medication optimization, adherence assessment, lifestyle intervention, and exclusion of secondary causes.