Late outcomes of renal denervation are more favourable than early ones: facts or fancies?

Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.