A Perspective on the Delivery of Renal Denervation Therapy Based on Pre-Clinical Data

RENAL DENERVATION FIELDThe release of unexpected results from the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial (1,2) has stimulated continued lively discussions and many hypotheses among believers and skeptics of renal denervation (RDN) therapy as to the potential confounding factors leading to the unanticipated outcome.Post hoc evaluation of the data has furthered these discussions and provided important insights.Hypotheses range from selection criteria of hypertensive enrollees as "resistant to medication" (3) and the Hawthorne effect (4), to catheter design (5), operator inexperience, insufficient amount of therapy delivery (6), and/or imprecise location of delivery, among others.Regardless, the impact of the SYMPLICITY HTN-3 trial was notorious and immediate.A large proportion of already skeptical clinicians were sufficiently swayed, and referrals for the therapy vanished, research suddenly dwindled, scientists divided among believers and nonbelievers along the RDN hypertension therapy fault line, and several companies abruptly terminated their RDN product line.Most other companies involved in the RDN field turned their focus on other products.Meanwhile, believers in RDN (i.e., clinicians, researchers, scientist, engineers, investors, and companies), and most importantly, hopeful patient advocates, anxiously await as Boston Scientific (REDUCE-HTN:REINFORCE [Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension Study]; NCT02439749) and Medtronic (SPYRAL HTN Global Clinical Trial Program: SPYRAL HTN-OFF MED [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439749 and SPYRAL HTN-ON MED [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multielectrode Renal Denervation System in Patients With Uncontrolled Hypertension on Standard Medical Therapy]; NCT02439775) continue with the next phase of clinical trials.