• Renal Disease
• Interventional Techniques & Devices
• Cardiology Clinical Trials
• Hypertension & Kidney Disease
• Hypertensive Disease

• Renal Disease
• Interventional Techniques & Devices
• Cardiology Clinical Trials
• Hypertension & Kidney Disease
• Cardiology & Cardiovascular Medicine
• Hypertensive Disease

Multiple factors associated with the Renal Denervation in Patients With Uncontrolled Hypertension trial [SYMPLICITY HTN-3; NCT01418261] may have contributed to its failure to meet the primary endpoint of change in office blood pressure at Month 6, according to George L. Bakris, MD, University of Chicago Medicine, Chicago, Illinois, USA, who presented data from a sub-analysis of this trial.

The sham arm of the SYMPLICITY HTN-3 trial demonstrated a greater than expected reduction in systolic blood pressure (SBP) [Bhatt DL et al. N Engl J Med 2014]. This may in part explain the lack of efficacy for the primary endpoint of the trial. The purpose of this sub-analysis was to determine the significance of several potential confounders that may have driven the effect observed in the sham arm, including procedural changes, change in antihypertensive therapy, variability in adherence, and differences in patient populations according to different geographic regions.

In the prospective, sham-controlled, SYMPLICITY HTN-3 trial, 535 patients with severe resistant hypertension were randomly assigned in a 2:1 fashion to undergo renal denervation (RDN) or a sham procedure. Resistant hypertension was defined as patients who had been prescribed 3 or more antihypertensive medications at maximally tolerated doses. There was no significant difference in change in SBP between the 2 arms at 6 months, as the sham arm demonstrated a significant change in SBP from baseline (p<0.001).

In the sub-analysis, procedural variability was analyzed such that the mean number of ablations in patients who underwent RDN was matched 1:1 using propensity scores. Patients were categorized according to 4 quadrant ablations in both, one, or neither renal artery. As the number of ablations increased, there was a trend toward a progressive decrease in office SBP in the patients who underwent RDN. There was, however, a similar, trend in the patients who underwent the sham procedure, with BP decreasing with an increasing number of ablations.

Baseline predictors of BP improvement in patients in the sham arm included the use of alpha-blockers, higher baseline office BP readings, the use of aldosterone antagonists, and the total number of intervention attempts. However, vasodilator use was inversely associated with response in both the sham and RDN arms. A secondary analysis of potential racial differences demonstrated that black patients were less likely to improve in the sham arm compared with patients who were not black.

Geographic location also led to some notable differences. Patients who lived in the Northeastern United States (Boston-New York region) demonstrated a change in office BP, albeit to a lesser extent in ambulatory BP. However, the results for patients living in the Southwestern, Southern, or Western United States reflected that of the original trial. It is unclear as to why there was a difference based on geographic location.

Dr. Bakris concluded by stating that there were some limitations in the SYMPLICITY HTN-3 trial that may have led to the neutral results with RDN for the primary endpoint. He further suggested that the limitations discussed in his presentation were exploratory and were meant to be hypothesis-generating.

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