Predictors of blood pressure response in the SYMPLICITY HTN-3 trial

Abstract

Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261.

Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure

“…16 We include here an analysis of the 6-month change in morning systolic BP based on the number of 4-quadrant ablations. Given the limited number of patients in HTN-Japan, patients with 1 (in either left or right) and 2 (in both the left and the right) renal arteries treated with 4-quadrant ablations were combined (denoted as at least 1 four-quadrant ablation) and compared with patients with no 4-quadrant ablations.…”

“…However, regardless of inherent racial differences, differences also existed between the 2 studies in terms of medications prescribed and the RDN procedure. Although patients in both SYMPLICITY HTN-3 and HTN-Japan received a similar number of antihypertensive medications, between baseline and 6 months, 39% of patients in SYMPLICITY HTN-3 underwent antihypertensive medication changes, 16 whereas only 7.3% of patients in HTN-Japan underwent antihypertensive medication changes (2 were in the RDN group and 1 was a control patient). 15 Some previous studies have examined the impact of RDN therapy on ABPM and its derived components.…”

“…Although recently reported results from the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3) 14 and SYMPLICITY HTN-Japan (HTN-Japan) 15 clinical trials did not demonstrate superiority of RDN over pharmacological management of hypertension based on superiority analyses of office BP or 24-hour ambulatory BP measurements (ABPM), 14,15 further evaluation of the SYMPLICITY HTN-3 trial identified several potential confounding factors that may have impacted the overall results, including insufficient ablation attempts, insufficient 4-quadrant ablations, and antihypertensive medication changes. 16 In contrast to the results of SYMPLICITY HTN-3, the recently reported prospective Renal Denervation for Hypertension (DENER HTN) 17 trial reported small but statistically significant reductions in ambulatory BP (though not office or home BP) in denervated patients compared with a nonblinded, randomized control group of patients with resistant hypertension treated with a stepped-care pharmacological strategy. These reductions included greater decreases in both daytime and nighttime ambulatory systolic BP in the denervated group.…”

Renal Denervation for the Treatment of Hypertension: Making a New Start, Getting It Right

“…In fact, post-hoc analysis has indicated that fewer than 25% of patients received complete bilateral treatment with ablations in a spiral pattern, with at least one ablation in each quadrant, as specified in the protocol. 6 • Another consequence of HTN-3, as experts pon-dered the unexpected result, was the growing real-ization that our previous understanding of the anatomy of the renal nerves might not have been entirely accurate. Indeed, further careful evaluation done largely since the trial was completed has established that many of the critical nerve fibers-including the afferent fibers that conduct messages to the central nervous system-come into close prox-imity to the renal arteries mainly at distal sites, often in the vicinity of the bifurcation of the arteries.…”

Renal Denervation in the Treatment of Resistant Hypertension: Results of a One-Year Observational Study

“…ст., в группе конт-роля (фальш-процедура) -11,7±25,9 мм рт. ст., то есть различия были статистически незначимыми [7]. Под-робный всесторонний анализ результатов Symplicity HTN-3 позволил выделить основные особенности ис-следования, которые определили негативные резуль-таты -это преимущественное воздействие на прокси-мальные отделы почечных артерий, значительная доля афроамериканцев, недостаточный опыт операторов и недоучет исходной комплаентности пациентов [8].…”