312
to prevent the thrombus formation and endothelium damage during RF RDN at the
ablation site. Furthermore, given the adventitial location of the renal SNS nerves,
saline irrigation might project ablation lesions deeper within the tissue, which
potentially may increase RDN effectiveness.
To date the most data concerning safety and effectiveness of RDN in treatment
of resistant hypertension comes from the Symplicity HTN-1, HTN-2, and HTN-3
trials. In these studies, RDN were done with single RF electrode catheter Symplicity.
Similar inclusion and exclusion criteria were used in all Symplicity trials, and these
studies involved patients in whom despite at least triple antihypertensive therapy
office systolic blood pressure (SBP) were not lower than 160 mmHg (150 mmHg in
the presence of diabetes type 2). In Symplicity HTN-3 trial besides the abovemen-
tioned office blood pressure criteria, additionally systolic 24 h ambulatory blood
pressure monitoring (ABPM) higher or equal 135 mmHg was required as inclusion
criterium. Exclusion criteria included eGFR <45 ml/min/1.73 m^2 , diabetes mellitus
type I, secondary causes of hypertension, and renovascular anatomical abnormali-
ties such as renal artery stenosis, previous angioplasty, or double and multiple renal
arteries. The first of these studies (Symplicity HTN-1) was a nonrandomized “proof
of concept” study [ 10 ]. In this study, 144 patients with resistant hypertension were
observed after RDN. A reduction of SBP by 27 mmHg and diastolic blood pressure
(DBP) by 17 mmHg at 6 months of follow-up was found. In the second study
(Symplicity HTN-2), 106 patients with resistant hypertension were randomly allo-
cated to RDN with previous treatment or to maintain previous treatment alone (con-
trol group) [ 11 ]. A SBP reduction of 32 and DBP reduction of 12 mmHg was
observed after renal denervation compared with the control group (1 and 0 mmHg,
respectively). Long-term data (36 months follow-up) from both abovementioned
studies showed that antihypertensive effect was maintained and even became
greater. Both these trials did not reveal any significant safety issues. However, there
were concerns about the design of the Symplicity HTN-1 and HTN-2 studies (lack
of ABPM and the unblinded design). To overcome these limitations, the prospec-
tive, single-blind, randomized, sham-controlled study was done (Symplicity HTN-
3) [ 12 ]. In this study, 535 patients with resistant hypertension were randomly
allocated to RDN or sham procedure (control group). Six months after procedure,
there was significant office SBP reduction from baseline in both groups (14 vs 12
mmHg, respectively), but between the active and control group, both office and 24
h ABPM did not differ significantly.
Results of the Symplicity HTN-3 study are difficult to interpret due to the num-
ber of methodological issues. Further analysis of data from Symplicity HTN-3 has
shown that only 19 patients (5%) had complete procedure of ablation that covered
360° of both renal arteries and only 68 patients complete procedure of ablation of
one renal artery. It might be linked to the fact that 60 of 111 operators performed
during the study only 1 or 2 renal denervation intervention. Office systolic BP in the
group with complete RDN procedure of both arteries was reduced by 24 ± 23 mmHg
in comparison to patients with incomplete RDN procedure where office SBP
decreased only by 14 ± 24. In contrast to previous studies conducted in Europe,
about 25% of patients in the Symplicity HTN-3 were African-Americans. There
M. Adamczak et al.