Renal denervation: from establishing effectiveness to measuring success

Renal denervation has emerged as a new therapeutic option for blood pressure (BP) control and is now incorporated into contemporary hypertension guidelines. Here, we review the evolution of evidence for renal denervation, approaches to assessing treatment response, and emerging technological developments.

Early non-sham-controlled trials of renal denervation showed substantial reductions in BP, whereas the first sham-controlled trial, SYMPLICITY HTN-3, yielded neutral findings. To address its limitations, subsequent trials incorporated key design modifications - including strict restriction of changes in background antihypertensive medications, procedural standardization, and separate conduct of trials in "on-medication" and "off-medication" cohorts - and have since consistently demonstrated the efficacy of renal denervation. In these studies, efficacy was assessed primarily by reductions in systolic BP, with additional measures including reductions in diastolic BP and antihypertensive medication burden. Alternative ablative mechanisms (e.g., alcohol-mediated neurolysis) are currently under investigation, along with multi-organ denervation approaches aimed at augmenting BP reduction while providing additional metabolic benefits.

Evidence supporting renal denervation has continued to accumulate, demonstrating consistent BP reductions. The field is evolving, with new approaches using alternative ablative mechanisms or targeting multi-organ sympathetic pathways on the horizon.