Predictors of blood pressure response in the SYMPLICITY HTN-3 trial

Abstract

Aims: 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.

Methods and 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.

Keywords: Renal denervation; Resistant hypertension; SYMPLICITY.

Figure 1

Change in office systolic blood pressure at 6 months for non-African-American and African-American subgroups (A) and for non-African-American and African-American subgroups according to baseline vasodilator use (B). P-values shown are for the difference between the 6-month change from baseline for the RDN group and the sham group. All 6-month change from baseline values are significant (P < 0.001).

Figure 2

The impact of number of ablation attempts on difference in 6-month change in office systolic blood pressure (A), 24-h ambulatory systolic blood pressure (B), and heart rate (C) between treated and matched sham patients. Baseline characteristics of the sham patients were propensity scored matched with the RDN patients. The SBP change measures for the RDN and matched sham patients, 95% confidence intervals, and P-values for the difference in change between the groups are shown.

Figure 3

Systolic blood pressure change at 6 months according to the ablation pattern. Change in office, ambulatory, and home systolic blood pressure at 6 months are shown based on delivery of ablations in four quadrants of the renal artery for both kidneys, one kidney, or neither kidney. A four-quadrant ablation is defined as one superior, one inferior, and two anterior/posterior ablations delivered.