What Is Happening in the Area of Device‐Based Blood Pressure Treatment?

Despite the publication of the surprisingly negative results of the Symplicity 3-HTN trial,1 and the multiple publications that have tried to address possible reasons for why this was a negative trial at odds with the positive results in prior device trials that had been performed primarily in Europe and Australia, interest continues in this modality. Current renal denervation (RDN) studies have profited from the key issues identified in the Symplicity HTN-3 trial that were predictive of systolic blood pressure response to RDN, including total number of ablation attempts, energy delivery in a four-quadrant pattern, preserved kidney function at baseline, and using a standardized hypertension regimen.2, 3 RDN is accomplished by delivering radiofrequency energy, or ultrasound energy, or ablative drugs to the space around the kidney arteries. The current round of studies will probably take a year to complete, but will be useful, if they are positive, in demonstrating the efficacy of this approach to blood pressure reduction. An alternative approach to RDN is to place an electrode over the baroreceptors located in the carotid bifurcation and “pace” this area with an electric signal. This simulates elevated blood pressure and provides negative feedback to the brainstem, which lowers blood pressure. The Rheos Pivotal trial of this approach failed to meet two of five primary endpoints, one of which was short-term efficacy.4 Nonetheless, interest remains in this approach and trials are underway in Europe. One improvement in the technology, addressing the second of the two primary endpoint failures, is the simplification of the electrode and the observation that only one of the carotid artery bifurcations needs to be treated to see efficacy.5, 6 Finally, a European trial recently demonstrated that the ROX coupler device (ROX Medical, San Clemente, CA),7 placed percutaneously from a femoral puncture, which creates a 4-mm arteriovenous fistula between the iliac artery and vein, was an effective way to lower blood pressure, although about a quarter of the patients had some venous complications in the follow-up period manifested by unilateral leg swelling and the need for venoplasty.8 There are several challenges facing the device-based intervention approaches to blood pressure treatment. The first and the largest is selection of patients. Who will best benefit from one or the other of these approaches? Secondly, will there be a better way to detect whether denervation of the kidney artery is adequate. Unlike baroreceptor stimulation or the ROX coupler approaches, which lower blood pressure almost instantaneously, RDN takes a minimum of 2 to 3 months to have a discernible effect on blood pressure. Finally, and perhaps of greatest concern to patients, will be the durability of the responses. So far, the Global Symplicity Registry and the long-term follow-up of the Rheos device suggest that beneficial effects on blood pressure appear to last for at least three years.4, 9 Even if nothing further develops from this field, it has caused a rejuvenation of interest in renal physiology, which, from the vantage point of these two nephrologists (the authors), is much welcomed!