Renal denervation in the antihypertensive arsenal - knowns and known unknowns

Abstract

Even though it has been more than a decade since renal denervation (RDN) was first used to treat hypertension and an intense effort on researching this therapy has been made, it is still not clear how RDN fits into the antihypertensive arsenal. There is no question that RDN lowers blood pressure (BP), it does so to an extent at best corresponding to one antihypertensive drug. The procedure has an excellent safety record. However, it remains clinically impossible to predict whose BP responds to RDN and whose does not. Long-term efficacy data on BP reduction are still unconvincing despite the recent results in the SPYRAL HTN-ON MED trial; experimental studies indicate that reinnervation is occurring after RDN. Although BP is an acceptable surrogate endpoint, there is complete lack of outcome data with RDN. Clear indications for RDN are lacking although patients with resistant hypertension, those with documented increase in activity of the sympathetic system and perhaps those who desire to take fewest medication may be considered.

FIGURE 1

Reduction in systolic and diastolic 24 h ambulatory blood pressure (mmHg) achieved by individual antihypertensive drugs and those observed in sham-RCTs comparing renal denervation to sham intervention. Shown data available in [9,127,128]. RCT, randomized controlled trial.

FIGURE 2

Sequential pairwise meta-analysis for mean change in 24-h ambulatory systolic blood pressure for sham-RCTs comparing renal denervation to sham intervention. Sequential pairwise meta-analysis for mean change in 24-h ambulatory systolic blood pressure is shown in the Figure for sham-RCTs comparing renal denervation to sham intervention. As heterogeneity was low, fixed effect meta-analysis was performed. The sham-RCTs were included in the sequential meta-analysis following the chronological order of publication and drawn boundaries were calculated using an adaptation of the continuous alpha-spending function. The sequential approach illustrates the trend of the accumulated evidence over time as the evidence becomes available in favor of renal denervation up to 6 months of follow-up. Crossing a boundary is indicative of strong evidence against the null hypothesis of equal mean differences between the interventions. As shown, the boundaries are already crossed following the addition of the 4th sham-RCT, with a summary mean difference favoring renal denervation of −2.76 (95% CI −4.93 to −0.59). Any additional sham-RCT available after that time-point, did not change the conclusive finding. CI, confidence interval; RCT, randomized controlled trial.