Resistant Hypertension and Renal Denervation. Considerations on the Results of the Symplicity HTN-3 Trial

Abstract

Resistant hypertension is undoubtedly a real clinical challenge, given that it increases cardiovascular events and has no effective treatment. Thus, it is easy to see why renal sympathetic denervation (RDN) has raised expectations among physicians treating patients with this serious disease. The SYMPLICITY HTN-1 trial was a proof-of-principle trial followed by the SYMPLICITY HTN-2 trial, which was a randomized unmasked trial that compared control patients and patients undergoing RDN therapy. Follow-up indicated significant and lasting reductions in blood pressure in the experimental group, thus raising expectations among physicians and patients. In fact, the European Society of Hypertension, the European Society of Cardiology, and an international panel of experts published position papers on RDN. In the same period, an RDN registry was set up in Europe with the participation of accredited centers. The registry has already collected data on more than 1500 patients. The recent publication of the SYMPLICITY HTN-3 trial, a single-blind, randomized, sham-controlled trial, confirmed that RDN is safe, but apparently lacks efficacy. Studies on RDN take the SYMPLICITY HTN-3 trial as the reference study and for this reason critics of the technique have suggested that the antihypertensive efficacy of RDN should be reconsidered in the light of its results. We consider that this viewpoint is questionable and analyze the reasons for our position. The SYMPLICITY HTN-3 trial followed an excellent design that randomized patients to RDN or a sham procedure. Analyses were based on the intention-to-treat principle. Thus, the trial included a control group to assess the possibility of a placebo effect. In fact, the SYMPLICITY HTN-1 and HTN-2 trials were accused of simply showing the placebo effect of the treatment on blood pressure. However, the conclusion that RDN lacks efficacy when compared with a sham procedure has been challenged. Firstly, there is insufficient evidence that blood pressure was stable during the RDN procedure in the SYMPLICITY HTN-3 trial in contrast to the SYMPLICITY HTN-1 and HTN-2 trials. The latter trials included long-term patients with high stable blood pressures