Predictors of blood pressure response in the SYMPLICITY HTN-3 trial.
OBJECTIVE
The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results.


RESULTS
Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern.


CONCLUSIONS
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.
Piedmont Heart Institute, Atlanta, GA, USA david.kandzari@piedmont.org.
David E
DE
Kandzari
Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
Deepak L
DL
Bhatt
Medtronic, Inc., Santa Rosa, CA, USA.
Sandeep
S
Brar
Emory University School of Medicine, Atlanta, GA, USA.
Chandan M
CM
Devireddy
Baker IDI Heart and Diabetes Institute, Monash University, Melbourne, Australia.
Murray
M
Esler
Medtronic, Inc., Santa Rosa, CA, USA.
Martin
M
Fahy
Wayne State University and the Detroit Medical Center, Detroit, MI, USA.
John M
JM
Flack
Baptist Cardiac and Vascular Institute, Miami, FL, USA.
Barry T
BT
Katzen
Emory University School of Medicine, Atlanta, GA, USA.
Janice
J
Lea
Stanford Hospital and Clinics, Palo Alto, CA, USA.
David P
DP
Lee
New York Presbyterian Hospital, Columbia University Medical Center and Cardiovascular Research Foundation, New York, NY, USA.
Martin B
MB
Leon
Stanford Hospital and Clinics, Palo Alto, CA, USA.
Adrian
A
Ma
Harvard Clinical Research Institute, Boston, MA, USA.
Joseph
J
Massaro
Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA Harvard Clinical Research Institute, Boston, MA, USA.
Laura
L
Mauri
University of Alabama at Birmingham, Birmingham, AL, USA.
Suzanne
S
Oparil
Division of Cardiology, Henry Ford Hospital, Detroit, MI, USA.
William W
WW
O'Neill
Duke University Medical Center, Durham, NC, USA.
Manesh R
MR
Patel
Prairie Heart Institute, Springfield, IL, USA.
Krishna
K
Rocha-Singh
The Ohio State University, Columbus, OH, USA.
Paul A
PA
Sobotka
Duke University Medical Center, Durham, NC, USA.
Laura
L
Svetkey
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Raymond R
RR
Townsend
The University of Chicago Medicine, Chicago, IL, USA.
George L
GL
Bakris
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D017115:Catheter Ablation / Q000379:methods; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney / Q000294:innervation*; D008297:Male; D008875:Middle Aged; D013562:Sympathectomy / Q000379:methods*; D016896:Treatment Outcome
Renal denervation; Resistant hypertension; SYMPLICITY