Global SYMPLICITY Substudy Teases out Reasons for Non-response in Real-World Patients

PARIS, France—Renal denervation has spurred much controversy in recent months, with the sham-controlled SYMPLICITY HTN-3 trial demonstrating little value to the novel procedure and the Global SYMPLICITY registry showing its efficacy. A subanalysis of that registry, presented Thursday, May 22 in a Hot Line session at EuroPCR 2014, dove deeper into the data to determine predictors of patient response.

Felix Mahfoud, MD, of Klinik für Innere Medizin III (Homburg/Saar, Germany), reviewed the positive results of the Global SYMPLICITY registry, presented in March at the 2014 American College of Cardiology/i2 Scientific Session. The registry enrolled 1,000 patients with uncontrolled hypertension who were treated with the Symplicity Catheter System (Medtronic, Mountain View, CA) at 231 international sites in 37 countries. Overall, patients experienced significant reductions in office systolic BP at 3 and 6 months.

Univariate analysis confirmed that both baseline office systolic BP (P < .0001) and overall average systolic BP (P = .05) predicted response to renal denervation.

On multivariate analysis, higher baseline office systolic BP and the presence of 2 or more comorbidities predicted overall response to renal denervation. Within a cohort of patients that mirrored the SYMPLICITY HTN-3 trial, predictors of response included higher number of ablation attempts, male sex, and higher baseline office systolic BP, while greater numbers of baseline antihypertensive drugs were associated with non-response (table 1).

Table 1. Predictors of Response to Renal Denervation

Moreover, in an angiographic model of the SYMPLICITY HTN-3-like cohort, baseline office systolic BP (OR 0.96; 95% CI 0.93-0.99; P = .015) predicted response. Mean diameter of renal arteries, on the other hand, tended to predict non-response (OR 1.48; 95% CI 0.91-2.26; P = .072).

Customized Therapy Might Strengthen Results

“It’s an interesting indicator that potentially we need to customize therapy delivering the energy successfully to the renal sympathetic nerves” depending on patient artery size, Dr. Mahfoud observed.

Limitations of the study, he continued, included the fact that definitions of non-response are “arbitrary” but have precedence in the literature. Also, the subgroups were limited by their small size.

Panelist Thomas F. Lüscher, MD, of University Hospital (Zurich, Switzerland), commented that the patients resembling those of SYMPLICITY HTN-3 “actually responded better, which is more difficult to reconcile.”

Dr. Mahfoud said this was likely driven by baseline BP being higher in this group. However, in some cases patients with low office BP but high 24-hour blood pressure—referred to as ‘masked hypertension’—are included in the registry and “mix up the analysis.”

Chaim Lotan, MD, of Hadassah University Hospital (Jerusalem, Israel), another panelist, said the subanalysis raises a lot of questions related to the catheter’s ability to fully ablate. In larger renal arteries, he suggested, perhaps “the nerves are further away” than in smaller arteries.

Dr. Mahfoud agreed, saying, “If you want to target the entire circumference of a bigger renal artery you need more ablations than in a smaller one.” This will influence the development of new devices, Dr. Lüscher commented.

Ron Waksman, MD, of Medstar Washington Hospital Center (Washington, DC), asked about operator experience and the effect on procedural success. Dr. Mahfoud replied that the relationship is still unknown since the registry only included experienced physicians. However, certain operators do seem to perform better than others, he added.

Joost Daemen, MD, of Erasmus Medical Center (Rotterdam, the Netherlands), asked about the predictive value of age “since SYMPLICITY HTN-3 showed…a strong correlation that people above 65 respond significantly less.” Although the analysis was run in the study, Dr. Mahfoud said, it did not reach statistical significance. “But we had the same impression that age is a predictor of nonresponse,” he replied.

 

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Source:
Mahfoud F. Responder and non-responder to catheter-based renal denervation in the real world – insights from the Global SYMPLICITY registry. Presented at: EuroPCR; May 22, 2014; Paris, France.

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