Proceedings From the 3rd European Clinical Consensus Conference for Clinical Trials in Device-based Hypertension Therapies

Felix Mahfoud; Michel Azizi; Sebastian Ewen; Atul Pathak; Christian Ukena; Peter J. Blankestijn; Michael Böhm; Michel Burnier; Gilles Chatellier; Isabelle Durand Zaleski; Guido Grassi; Michael Joner; David E. Kandzari; Ajay Kirtane; Sverre E. Kjeldsen; Melvin D. Lobo; Thomas F. Lüscher; John William McEvoy; Gianfranco Parati; Patrick Rossignol; Luis Ruilope; Markus P. Schlaich; Atif Shahzad; Faisal Sharif; Andrew S.P. Sharp; Horst Sievert; Massimo Volpe; Michael A.Weber; Roland E. Schmieder; Costas Tsioufis; William Wijns

Disclosures

Eur Heart J. 2020;41(16):1588-1599. 

In This Article

Abstract and Introduction

Introduction

Device-based hypertension treatment is a complementary and possibly alternative approach to conventional lifestyle changes combined with antihypertensive medications to achieve and maintain optimal blood pressure (BP) control. A series of clinical trials assessing novel technologies are currently ongoing for device-based hypertension treatment, including endovascular catheter-based renal denervation (RDN), baroreceptor activation therapy, endovascular baroreflex amplification, and cardiac pacemaker-mediated hypertension treatment.

Only a few years ago, RDN was written off as ineffective after results of the sham-controlled SYMPLICITY HTN-3 trial[1] failed to confirm early trials' reports of significant BP reductions in patients resistant to guideline-based combination drug therapy. However, the trial's design and execution has been questioned by many. Later-on, following recommendations provided by European and US expert groups,[2–4] defining optimal trial design and methodology and the population of patients to be included, three carefully designed, randomized sham-controlled RDN trials (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE-HTN SOLO)[5–8] reported consistent, plausible, and clinically meaningful ambulatory and office BP reductions in the short- (2 to 3 months) and mid-term (6 months) with radiofrequency (RF)- or highly focused ultrasound (US)-based RDN while reporting no serious adverse events. These exploratory phase II studies included selected patients with uncontrolled hypertension who were both on and off medications to demonstrate both biological proof of principle (off medications) but also context in routine clinical practice (on medications). With rigorous trial oversight and methods, these studies provided consistent and robust proof for BP lowering efficacy of RDN.

Against this background, the 3rd European Clinical Consensus Conference for device-based therapies for hypertension was held in July 2019 in Mainz, Germany. The aims were to identify key issues and provide consensus recommendations for the design and conduct of new, clinically more relevant, pragmatic trials to move forward with the investigation of device-based hypertension therapies, and to establish what evidence is needed for potential clinical adoption of these technologies (Figure 1). Considerations on how to interact with regulatory and reimbursement authorities were also discussed. The current document summarizes the discussion and consensus views. It focuses on research and development issues and is not a guide to clinical practice (Take home figure).

Figure 1.

Explanatory vs. pragmatic trial on the example of RDN. Adapted from Thorpe et al.9

Take home Figure.

Summary of research and development challenges in device-based hypertension treatment.

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