Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension

Abstract

C atheter-based renal denervation (RDN) has been considered as a new hope for patients with resistant hypertension (RH). The first studies published by the same pioneering group of experts 1,2 triggered widespread enthusiasm, and the new method was quickly promulgated. 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.3-6 Based on these results, the Czech Society for Hypertension does not recommend implementation of RDN in routine practice. 8This study seeks to evaluate the efficacy of RDN in a prospective multicenter randomized trial with the acronym PRAGUE-15 in patients with true RH. Twenty-four-hour ambulatory blood pressure monitoring, exclusion of secondary hypertension, and evaluation of treatment compliance served as confirmation of true resistance. The efficacy of RDN was compared with intensified antihypertensive treatment, including the use of spironolactone. The 6-month results of the PRAGUE-15 study were previously published. 6 To date, only 1 properly designed study has published 12-month results 9 where RDN was compared with a sham procedure. Here we present the 1-year data, including the evaluation of renal artery changes after RDN and hormonal and hemodynamic parameters. See Editorial Commentary, pp 278-280Abstract-This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Renal denervation in the era of HTN-3. Comprehensive review and glimpse into the future

“…Eplerenone was offered as an alternative but was rejected by all patients due to financial costs. Twelve-month results were recently published 43 and corroborated that RDN was not superior to intensified drug-treatment during this period. Per-protocol analysis showed a significant reduction in 24-hour systolic BP, more accentuated in the pharmacological cohort, with evident betweengroup difference (P ¼ .04).…”

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients

“…In two trials, only ambulatory BP measurements[56] were available, while both office and ambulatory BP were collected in the seven remaining trials. The maximum length of follow-up was at least 6 months in all studies, and up to 12 months in three trials[161718] and 36 months in one trial. [19] There were five other trials[23569] designed not to alter antihypertensive medication during the follow-up.…”

“…[1619] There was no significant difference between the two groups [MD = 0.69 mmHg; 95% CI : −4.2–5.58; P = 0.78; Figure 6], and no heterogeneity of the pooled effect ( I 2 = 0%; P = 0.37).…”

Vascular Mineralocorticoid Receptors

“…46 In the PRAGUE-15 trial, spironolactone treatment reduced blood pressure more effectively than catheter-based renal denervation in patients with resistant hypertension on optimized background pharmacotherapy. 47 Although further trials are required to confirm these promising results in a larger population, a renaissance of MR antagonists for the treatment of arterial hypertension can be expected.…”