Renal denervation: back to reality, finally!

In the review published in the present issue of European Heart Journal – Cardiovascular Pharmacotherapy, 1 Kjeldsen and co-authors provided a comprehensive state of the art on renal denervation (RDN), updated at September 2014. The article depicts accurately the rise and fall of the use of RDN in treatment-resistant hypertension (TRH), and the abrupt change in the scientific community's opinion provoked by the publication of the results of the Simplicity HTN-3 study. 2 It is now recognized that the enthusiasm raised after the publication of the first proof-of-concept studies was exaggerated and that more caution would have been more appropriate. The solitary role of the industry in promoting research on RDN, the heavy marketing campaign conducted before solid scientific evidence was obtained, and many pitfalls in the design of the early studies had been highlighted even before the publication of the Simplicity HTN-3 study. 3 , 4 Furthermore, some negative results were published as well. 5 , 6 The publication of the Simplicity HTN-3 study finally awakened from ‘el sueño de la razón’ the European regulatory authorities that allowed reimbursement of RDN on the basis of an amount of evidence that would have never been considered sufficient for an anti-hypertensive drug, and conceivably will put an end to indiscriminate, routine use of this procedure in many public and private cath labs. However, maybe the greatest merit of this trial is to have finally put the debate on RDN in the framework of a rational, scientific discussion. In this context, the authors of the present review are maybe archiving too quickly the limitations of the Simplicity HTN-3 study merely as justifications for the negative result. On the contrary, since the physiopathological background of RDN is sound and solid and the safety of the procedure has been established, in our opinion it is time to consider from the scientific point of view some crucial aspects that may have influenced the outcome, such as experience of the recruiting centers and of the operators, and quantity, technique and site of energy delivery, that have been overlooked in previous studies and advocated as causes of failure for the Simplicity HTN-3. We also sincerely hope that in the next future, with an only investigational use of RDN in the hands of referral centers, future trials will be aimed at identifying predictors of response to RDN, thus finally defining the correct indication for this procedure. In fact, despite TRH is the most ethical target population to test a novel treatment, it is not necessarily the most adequate from the pathophysiological point of view. While sympathetic overactivity is present in essential hypertension at every stage and conceivably plays a pathogenetic role, 7 accrued vascular and renal organ damage, which can be irreversible or reversible only after a long period of time, might perpetuate refractoriness to treatment even after removal of its cause. On the contrary, it is reasonable to hypothesize that newly diagnosed hypertensive patients in whom sympathetic overactivity is demonstrated could be a better target population for RDN than TRH. Kjeldsen and co-authors concluded with an overview of current literature about the use of drug monitoring in TRH, proposing it not only for diagnostic but also for therapeutic purposes, as recently supported by preliminary data. 8 There is still paucity of data about how to improve compliance to non-pharmacological and pharmacological treatment in resistant hypertensive patients, and probably a more empathic relationship with the patient might help. In this view, hypertension specialists should be careful not to negatively label the patient, and the use of therapeutic drug monitoring results should always be accompanied by counselling of methods to overcome barriers to adherence. 8 Treatment-resistant hypertension (TRH) patients that are intolerant to many anti-hypertensive drugs might probably still benefit from device-based therapies such as RDN.