AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Renal Denervation versus Optimal Medical Therapy for Resistant Hypertension: Long-Term Cardiovascular Outcomes — A Systematic Review and Meta-Analysis of Sham-Controlled Trials
By Krishnan E, Hizomi A, Syed Khaja A et al.
Background: Resistant hypertension (RH) — uncontrolled BP on ≥3 maximally dosed agents including a diuretic — affects 12-15% of hypertensive adults and carries disproportionate MACE risk. Catheter-based renal denervation (RDN) has re-emerged after sham-controlled trials demonstrated significant ambulatory BP reductions. Whether these hemodynamic gains translate into long-term hard cardiovascular outcomes has not been pooled. This is the first meta-analysis restricted to sham-controlled RDN trials reporting MACE data beyond 12 months. Methods: Following PRISMA 2020, we searched MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through March 2025. Eligible studies were randomized sham-controlled trials of RDN in confirmed RH with ≥12-month follow-up and MACE reporting. Primary outcomes: MACE (CV death, non-fatal MI, non-fatal stroke) and 24-hour ambulatory systolic BP (ASBP) reduction. Secondary outcomes included antihypertensive pill burden, renal function, and procedural safety. Pooled MDs and RRs used random-effects models; ASBP-MACE dose-response assessed by meta-regression. Results: Sixteen sham-controlled trials (n=5,892; baseline ASBP 165.4 ± 14.2 mmHg; median follow-up 28 months) were included. RDN significantly reduced 24-hour ASBP (MD –8.7 mmHg, 95% CI –11.2 to –6.2; p<0.0001; I ² =31%). MACE was significantly lower with RDN (RR 0.76, 95% CI 0.64-0.90; p=0.002); stroke was reduced by 34% (RR 0.66, 95% CI 0.49-0.88; p=0.005). Meta-regression confirmed a significant ASBP-MACE dose-response (β=–0.021; p=0.003). Antihypertensive burden decreased by 0.8 agents (p<0.0001). Procedural serious adverse events occurred in 1.2%. Conclusions: Renal denervation produces durable BP reduction that translates into significant MACE and stroke reduction in sham-controlled trials. The ASBP-MACE dose-response confirms hemodynamic mediation of cardiovascular benefit. Current AHA resistant hypertension guidelines do not include RDN as a therapeutic option; this sham-controlled pooled evidence base supports formal guideline consideration as an adjunctive strategy in true RH. An adequately powered, outcomes-primary RDN trial is now the logical next step.