Author + information
- John D. Bisognano, MD, PhD⁎ (, )
- George Bakris, MD,
- Mitra K. Nadim, MD,
- Luis Sanchez, MD,
- Abraham A. Kroon, MD, PhD,
- Jill E. Schafer, MS,
- Peter W. de Leeuw, MD, PhD and
- Domenic A. Sica, MD
- ↵⁎Department of Medicine, Cardiology Division, University of Rochester Medical Center, 601 Elmwood Avenue, Box 679-7, Rochester, New York 14642-8679
We thank Dr. Tsioufis and colleagues for their recent letter regarding the Rheos Pivotal Trial (1). We provide the following clarifications based on their original comments.
1. Was blood pressure (BP) adequately characterized in the Rheos Pivotal Trial? The BpTRU (BpTRU Medical Devices, Coquitlam, British Columbia, Canada) repeated-measures protocol (1) was used throughout the trial to measure BP. BpTRU was selected for its correlation with and low bias in estimating daytime ambulatory BP (2–4). Trial qualification requirements summarized in our paper are correct but incomplete: systolic blood pressure (SBP) ≥160 mm Hg according to the BpTRU protocol was mandatory, along with 2 office cuff readings of SBP ≥160 mm Hg within 3 months of enrollment. Resistant hypertension was assured by requiring 24-h average ambulatory SBP ≥135 mm Hg and ≥1 month of ≥3 concomitant antihypertensive medications.
Short-term assessment of baroreflex activation therapy (BAT) response was suboptimal, comprised by the BP difference between only 2 time points: months 0 and 6. Month 0 proved an inadequate baseline, whereas high intraindividual BP variability generated excess false-positive findings in the control group (1). Baseline measurement involving longitudinal BP free of surgical effects would presumably improve statistical power.
Dr. Tsioufis and colleagues postulate that ambulatory data would alleviate intrapatient BP variability. Although ambulatory BP could provide supportive findings, such as attenuation of morning surge, its correlation with BpTRU would make redundant much of the benefit. In any case, greater reduction of SBP and increased rate of attaining goal BP among patients receiving BAT stand as clear indicators of therapeutic benefit.
2. Are results uniformly consistent with the assertion that BP reductions ensue from BAT? Along with BpTRU measurements, data on vital signs, medications, and medication adherence were collected. Dr. Tsioufis and colleagues conjecture that BP reductions associated with BAT could result from intensified medical therapy. Between months 0 and 6, the number of prescribed medications decreased in groups A and B by 0.5 and 0.7, respectively (p ≤ 0.001). Medication remained reduced at month 12. No significant differences in number of medications or use of aldosterone antagonists were observed between groups A and B. Medication adherence was stable. Thus, increased medication was not responsible for the reductions in BP observed with BAT.
Dr. Tsioufis and colleagues suggest reductions in heart rate (HR) accompanying reduced BP could corroborate BAT efficacy. Despite the high prevalence of beta-blockers and sympatholytic agents, HR was significantly reduced among responders in group A (−4.2 beats/min; p = 0.01) but not in group B or among nonresponders in either group. More impressively, significant correlations were observed between reductions in BP and HR in group A at 6 and 12 months and in group B at 12 months (r = 0.21 to 0.26; all p ≤ 0.02) but not at 6 months. Thus, BP reductions with BAT were consistently correlated with reduced HR.
3. Is the risk-benefit profile of BAT appropriate for resistant hypertension? BP was clearly reduced among patients with resistant hypertension receiving BAT. Moreover, design of the next-generation implantable barostimulation device, the Barostim neo (CVRx, Inc., Minneapolis, Minnesota) emphasizes safety. To date, neo has demonstrated an excellent safety profile in 40 implanted patients in Europe and Canada. In addition to reaffirming the established clinical benefits of BAT, we expect to soon demonstrate safety of the Barostim neo in a randomized, controlled study of patients with resistant hypertension.
Please note: Dr. Bisognano is a consultant for, has received research support from, and is a member of the scientific advisory board of CVRx. Dr. Bakris is a consultant for CVRx, Takeda, Abbott, Relapysa, and Medtronic; and a principal investigator for Medtronic and Relapysa; Dr. Nadim is on the advisory board of CVRx. Ms. Schafer if a former employee of and a current paid consultant for CVRx. Dr. de Leeuw has received a research grant from CVRx. Dr. Sica is a consultant for CVRx. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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