Pirdehghan, Reza

Introduction: Resistant and uncontrolled hypertension pose persistent clinical and public health challenges. Renal denervation, a catheter-based procedure targeting renal sympathetic nerves, has emerged as a promising approach to lower blood pressure by reducing sympathetic overactivity. Hypothesis: A systematic review and meta-analysis of sham-controlled trials investigated whether renal denervation results in sustained blood pressure reduction across short-, medium-, and long-term follow-up. Methods: We searched PubMed, Embase, CENTRAL, and Web of Science through March 2025. The protocol was registered in PROSPERO (CRD420251015937). Randomized, sham-controlled trials of renal denervation in resistant/uncontrolled hypertension were included. Primary outcomes were ambulatory blood pressure (daytime, nighttime, and 24-hour); secondary outcomes included office and home blood pressure measurements. Follow-up durations were categorized into three groups: less than 6 months, 6–12 months, and greater than 12 months. Risk of bias was assessed using RoB-2. Results: Twenty trials (25 reports) with 2,167 RDN patients and 1,744 sham controls were included. Most trials had a low risk of bias. RDN significantly reduced 24-hour SBP (–3.29 mmHg, 95% CI: –5.91 to –0.67) and DBP (–1.42 mmHg, 95% CI: –2.29 to –0.55), despite high heterogeneity (I2 > 90%). Daytime DBP showed a significant reduction (–2.90 mmHg, 95% CI: –4.39 to –1.41), while other BP measures were less consistent. Home SBP was significantly reduced (–5.04 mmHg, 95% CI: –8.50 to –1.58). At 6–12 months, 24-hour SBP reduction persisted (–3.36 mmHg, 95% CI: –5.71 to –1.01), but DBP effects were nonsignificant. Long-term follow-up revealed nonsignificant changes in systolic blood pressure and diastolic blood pressure. Conclusions: Renal denervation modestly lowers BP in the short term (<6 months). Mid-term SBP reduction persists, but diastolic and long-term effects are inconsistent. These findings highlight the need for refined patient selection, optimized techniques, and longer follow-up trials.