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(DEBuT-HT) confirmed safety and efficacy of the BAT system in 45 resistant
hypertensive patients who had significant reductions in blood pressure 3 months
after the initiation of therapy which were sustained at 2 years of follow-up [ 38 ].
Following these promising results, the randomized, double-blind placebo con-
trolled, Phase III Rheos pivotal trial in 265 patients with resistant hypertension was
successful in meeting the predetermined sustained efficacy end point with 81% of
the group having a reduction of systolic blood pressure of at least 10 mmHg at
12 months of the magnitude at least 50% of that obtained at month 6. However, the
efficacy criterion remained unmet because the proportion of patients with blood
pressure reduction at 6 months of at least 10 mmHg was only marginally greater in
the BAT group as compared to placebo. This result was likely due to a less-than
optimal trial design, as patients with inactive implants (placebo) had a larger reduc-
tion in systolic blood pressure than expected [ 39 ]. Notwithstanding, this trial
emphasized the promise of BAT for the treatment of resistant hypertension as all
patients receiving BAT had more than 30 mmHg reductions in their systolic blood
pressure at 12 months, and this reduction was sustained for an average of 28 months
follow-up [ 40 ]. Recent developments in the design and approach of BAT led to the
Barostim neo, comprising a miniaturized electrode implanted unilaterally, with
obvious benefits brought about by the reduction in the invasiveness of the implant
procedure. The Barostim neo has demonstrated efficacy in significantly reducing
systolic blood pressure by more than 25 mmHg in a trial on 30 resistant hyperten-
sive patients at 6 months of follow-up and demonstrated a benign short- and long-
term safety profile [ 41 ]. Stemming from this initial findings, a larger, FDA-approved
multicenter randomized double-blind pivotal clinical trial is ongoing (The US
Barostim Hypertension Pivotal Trial, NCT01679132), randomizing patients with
resistant hypertension to receiving optimal medical management therapy with or
without BAT.
The mechanisms involved in the blood pressure reduction by BAT have been
explored in animal models and largely confirmed in humans. These studies suggest
that global sympathoinhibition and concomitant suppression of renin secretion,
likely mediated by reductions in renal sympathetic nerve activity, are the key mech-
anisms whereby BAT lowers blood pressure [ 4 , 15 ]. Although the renal sympathetic
nerves provide the apparent link between suppression of central sympathetic out-
flow and the reduction in blood pressure, experimental [ 42 ] and clinical [ 43 ] evi-
dence indicate that BAT is capable of lowering blood pressure even when the renal
nerves are not present. Although the mechanisms responsible for the blood pressure
lowering effect of BAT in the absence of renal nerves are not evident and have not
been explored to date, several mechanisms have been identified as potential candi-
dates, including increased natriuretic peptides or renal interstitial pressure in an in
silico study using a complex and established mathematical model of human physi-
ology [ 44 ]. While these mechanisms warrant further investigation, it is conceivable
that global sympathetic suppression by BAT may activate redundant natriuretic fac-
tors whose role only becomes apparent when sympathoinhibition does not include
the renal nerves.
R. Iliescu and D.N. Şerban