O89 POOLED, LONG-TERM ANALYSIS OF THE GLOBAL SYMPLICITY CLINICAL TRIAL PROGRAM OF RADIOFREQUENCY RENAL DENERVATION FOR THE TREATMENT OF UNCONTROLLED HYPERTENSION

Background/Objective: The Global Symplicity Clinical program is the largest investigation of radiofrequency renal denervation (RDN) to treat uncontrolled hypertension (HTN) to date. Over 4,000 patients enrolled into Spyral First-in-Man, Global SYMPLICITY Registry DEFINE, and multiple randomized, controlled and sham controlled trials including HTN-Japan, Symplicity HTN-3, SPYRAL HTN-OFF and -ON MED studies. We leveraged the entire Symplicity Global Clinical program dataset to develop a multivariate, patient-level, mixed model assessing (1) long-term BP reductions after RDN, and (2) whether specific patient characteristics correlate with future BP reductions after the procedure. Methods: Repeated BP measurements from each patient in the Global Symplicity Clinical program were analyzed using linear mixed models fitted with 24-h ambulatory systolic (S)BP and office SBP as outcome variables. Baseline SBP, baseline number of antihypertensive (AH) medications, and AH medications over time were included as fixed effects. Additional patient characteristics were included as potential significant fixed effects. To account for multiple BP measurements per patient and multiple studies, nested random effects were included using an auto-regressive correlation structure. Results: Data from 4156 patients treated with either the first-generation Symplicity Flex or the next-generation Symplicity Spyral catheter. Estimated, office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic with a steep reduction after RDN through the first 6 months (Figure), followed by a steady reduction in SBP afterward through 36 months. Higher baseline SBP was correlated with greater BP reductions. AF history (-3.7 mmHg compared to no AF, p=0.0048) and increasing eGFR at baseline (-0.039 mmHg for every 1 ml/min increase in baseline eGFR, p=0.040) significantly correlated with lower 24-h ambulatory SBP. Conclusion: This is the most comprehensive analysis of radiofrequency RDN to date. Higher baseline SBP was strongly correlated with greater BP reductions. The results demonstrate the durability of RDN as an adjunctive therapy to treat HTN. Prospective studies need to validate whether certain patient characteristics are associated with improved response to RDN.