Towards Establishing Renal Denervation as the Third Pillar in Hypertension Treatment: The RADIANCE-HTN TRIO Trial

Abstract

Hypertension remains the leading modifiable risk factor for major adverse cardiovascular outcomes with a global burden of 10.8 million deaths directly attributable to uncontrolled blood pressure in 2019 (BP) [1]. Lifestyle modification and pharmacotherapy represent the two major strategies applied in general practice to lower BP, and rightly so. Sustained efforts to comply with a healthy lifestyle and adherence with prescribed antihypertensive therapy, even more so when the two are combined, have substantial BP lowering efficacy in most persons affected. Importantly, BP lowering per se is one of the most impactful interventions in medicine with a recent patientlevel data meta-analysis demonstrating that a 5 mmHg office systolic BP reduction is associated with a 10% reduction in major cardiovascular events [2]. The big catch is that while the above has been known for years, we have barely made any progress in achieving BP control rates which are stagnating below 50% globally. The need for the development of alternative approaches to lower BP is obvious and provided the background for revisiting an old therapeutic concept, namely targeting the renal nerves which, through their regulatory role on blood flow, sodium and water homeostasis, and renin release, integrate 3 major mechanisms of BP control. The general principles of catheter-based ablation strategies to target these renal nerves located in the adventitia surrounding the renal arteries were easily applicable and indeed first tested in Australia. The SYMPLICITY HTN-1 and 2 studies provided first proof-of-concept and RCT data to demonstrate the safety and efficacy of endoluminal radiofrequency (RF) ablation as a means to lower BP in patients with resistant hypertension. SYMPLICITY HTN-3, the first sham-controlled study failed to show BP lowering efficacy beyond that of a sham-procedure owing predominantly to an unprecedented sham-effect, operator inexperience, and patient selection and adherence issues. Nevertheless, subsequent sham-controlled trials applying next generation ablation technologies, improved study design, assessment of medication adherence, and ambulatory BP as the primary outcome measures, uniformly demonstrated clinically relevant BP reductions with RDN in both untreated (SPYRAL HTN-OFF MED [3], RADIANCE-HTN SOLO [4] and hypertensive patients on concomitant medication (SPYRAL HTN-ON MED). These findings unequivocally proof the validity of the underlying concept but also & Markus P. Schlaich [email protected]