Renal Denervation for Treatment of Hypertension: a Second Start and New Challenges.

Abstract

Following the publication of the randomized controlled but open-label trial Symplicity HTN-2, catheter-based renal sympathetic denervation was proposed as a novel treatment for drug-resistant hypertension. Thousands of procedures were routinely performed in Europe, Australia and Asia, and many observational studies were published. A sudden shift from overoptimistic views to radical scepticism occurred later, when the large US randomized sham-controlled trial Symplicity HTN-3 failed to meet its primary blood pressure lowering efficacy endpoint. Experts are divided on the reasons accounting for the large discrepancy between the results of initial studies and those of Symplicity HTN-3. Indeed, the blood pressure lowering effect associated with renal denervation was overestimated in initial trials due to various patient and physician-related biases, whereas it could have been underestimated in Symplicity HTN-3, which was well designed but not rigorously executed. Still, there is a large consensus on the need to further study catheter-based renal denervation in more controlled conditions, with particular emphasis on identification of predictors of blood pressure response. US and European experts have recently issued very similar recommendations on design of upcoming trials, procedural aspects, drug treatment, patient population and inclusion-exclusion criteria. Application of these new standards may represent a second chance for renal denervation to demonstrate--or not--its efficacy and safety in various patient populations. With its highly standardized treatment regimen, the French trial DENERHTN paved the way for this new approach and may inspire upcoming studies testing novel renal denervation systems in different populations.