The five RADIANCE-HTN and SPYRAL-HTN randomised studies suggest that the BP lowering effect of RDN corresponds to the effect of one antihypertensive drug.

Renal denervation (RDN) may be a new treatment modality for patients with hypertension. Initially, efforts to test the efficacy of RDN in lowering blood pressure (BP) have focussed on patients with apparent treatment resistant hypertension (aTRH). The SYMPLICITY HTN2 trial [1] reported a major reduction in systolic BP with RDN in patients with aTRH using office-based BP measurement. However, using ambulatory BP, the state-ofthe art technique for measuring BP in patients with aTRH [2], BP reductions were less evident [1]. Further, since poor drug adherence, which is common in aTRH [3], was not monitored in SYMPLICITY HTN-2, interpretation of the study results could be confounded by the Hawthorne effect i.e. patients started taking their drugs as prescribed in response to the attention devoted to them [4]. SYMPLICITY HTN-3 [5] included a sham control group and ambulatory BP measurements that balanced the Hawthorne and white-coat, placebo, and regressionto-the–mean effects, resulting in a BP reduction of 2mmHg in the RDN treatment group compared to the sham control. Further, meta-analyses of the first generation of randomised controlled studies of RDN did not show BP lowering effects of RDN (Figures 1 and 2), whether or not SYMPLICITY HTN-3 was included [6], and whether or not a sham control (Figures 3 and 4) was a part of the design [7]. However, these disappointments [5–7] did not end the interest in RDN for many reasons. First, total abdominal sympathectomy resulting from surgical splanchnicectomy was highly effective in the treatment of severe hypertension in cohorts of patients reported in the 1930s [8] and 1950s [9,10]. Second, the meta-analyses showed that RDN did not lead to severe adverse events and could be considered safe [6,7]. Third, the role of the sympathetic nervous system in the pathophysiology of hypertension is strong [11,12]. Further, the procedural problems that contributed to the failure of early RDN trials to lower BP could be overcome [13,14]. Therefore, new protocols were designed to assess the antihypertensive efficacy of RDN. One new approach was to perform clinical studies in untreated hypertensive