Randomized Sham-Controlled Trial of Renal Sympathetic Denervation in Mild Resistant Hypertension

Abstract

R esistant hypertension is defined as a blood pressure (BP) of ≥140/90 mm Hg despite the intake of ≥3 antihypertensive drugs, including a diuretic at maximally tolerated doses. 1 Its prevalence has been reported to be 12.8% in a US population.2 Sympathetic overactivity contributes to the development and perpetuation in a subset of patients with resistant hypertension.3 Its negative effects include sodium and water retention, increased renin release, and alterations of renal blood flow. 3Afferent and efferent sympathetic nerves that travel in the renal artery walls mediate pathological interactions between the central nervous system and the kidneys. Recently, catheterbased disruption of these renal sympathetic nerve fibers using radiofrequency energy has been introduced as a new treatment against resistant hypertension. Initial nonrandomized and randomized, nonblinded trials demonstrated a dramatic reduction in systolic and diastolic BP after renal sympathetic denervation (RSD). 4,5 In contrast, in the recent sham-controlled Simplicity HTN-3 trial of patients with severe treatment-resistant hypertension, RSD led to no significant improvement in BP when compared with the sham group.6 Some think that the results of this trial with the so far most rigorous design commenced the beginning of the end of RSD for resistant hypertension. Proponents of RSD argue that the negative outcome is a consequence of inefficient denervation procedures and suboptimal selection of patients. One aspect that deserves further consideration is that patients recruited into the Simplicity HTN-3 study might represent a population at the most advanced spectrum of the disease with marked and in many cases long-standing hypertension. One could argue that in such patients, RSD might be less effective because of irreversible alterations of the anatomic structures and physiological processes supporting chronic BP elevations. The present trial was conducted to test the hypothesis that RSD is superior to a sham intervention in patients with only mild resistant arterial hypertension. Methods Design OverviewThe trial's main objective was to study a possible blood-pressure lowering effect of RSD in patients with resistant hypertension and mildly elevated BP. Eligible patients between 18 and 75 years of age were randomized to RSD or a sham procedure. Resistant hypertension with mildly elevated BP was defined as (1) a stable antihypertensive drug Abstract-Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat po...

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation

“…13 The average 24-hour SBP decrease after RD was 16 mm Hg in the DENERHTN trial as compared with 7 mm Hg in the SYMPLICITY HTN III trial, 14 despite lower baseline values (152 mm Hg versus 159 mm Hg, respectively). In another randomized sham-controlled trial, 15 RD reduced 24-hour SBP significantly more than did antihypertensive treatment in patients with RH (−8.3 mm Hg versus −3.5 mm Hg in the per-protocol analysis; P=0.04), this smaller BP lowering effect than in our study being accounted for by lower baseline 24-hour SBP values (140 mm Hg).…”

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension

“…These changes might be attenuated by the fact that only 19 patients were able to continue spironolactone treatment within 12 months. The fact that no additional changes in RDN (except for BP reduction) were observed, together with the current results of the perprotocol cohort and knowledge of the results of sham procedure studies, 5,9 questions the real long-term efficacy of RDN. Similarly, the results of later animal studies cast doubts upon the lasting effect of catheter-based RDN when reinnervation was proved even after 5.5 months.…”

“…However, this was slowed down in 2014 by publication of trials with negative results for RDN. [3][4][5][6] Apart from exceptions, 7 most of these studies failed to prove the satisfactory efficacy of RDN.…”

“…[3][4][5][6] Apart from exceptions, 7 most of these studies failed to prove the satisfactory efficacy of RDN. [3][4][5][6] Based on these results, the Czech Society for Hypertension does not recommend implementation of RDN in routine practice. 8 This study seeks to evaluate the efficacy of RDN in a prospective multicenter randomized trial with the acronym PRAGUE-15 in patients with true RH.…”

Recent advances in the pathophysiology of arterial hypertension - potential implications for clinical practice

“…Given that in hypervolemia in physiological conditions hypertension and hyperosmolality inhibit AVP secretion, these findings suggested that RH was associated with impaired biosynthesis and chronic stimulation of vasopressinergic neurons, subsequent circumferential renal nerves ablation was actually achieved. 85,86 On the contrary, the recently reported renal denervation for hypertension study, a prospective, open -label randomized controlled trial with blinded 24 -hour ambulatory BP endpoint evaluation in patients with RH demonstrated that effectiveness in BP lowering is greater when RDN is added to a standardized stepped -care antihypertensive treatment when compared to the same medication alone. 76 The 6 -month primary efficacy endpoint which was a reduction in daytime systolic BP was met (-15.8 mm Hg in the RDN vs -9.9 mm Hg in the control arm).…”