Ressource pédagogique : Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 : Resistant hypertension trials: Can renal denervation therapy lower blood pressure?

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Title : Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 : Resistant hypertension trials: Can renal denervation therapy lower blood pressure? Speaker: Felix MAHFOUD, Homburg, GER Discussant: Michel AZIZI, Paris, FRA Abstract : Renal Denervation: Caution is still required Despite the availability of multiple classes of orally active antihypertensive treatments, resistant hypertension remains an important public health issue in 2012. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments. A new catheter system using radiofrequency energy has been developed, allowing a percutaneous endovascular approach to renal denervation and providing patients with resistant hypertension with a new therapeutic option. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected uncontrolled hypertensive patients with suitable renal artery anatomy. The available evidence suggests a favorable blood pressure (BP)-lowering effect in the short-term and a low incidence of immediate local and endovascular complications. This follow-up period is, however, too short for the detection of rare or late-onset adverse events. Published studies are subjected to several limitations inherent to their openlabel design subject to expectation, performance and evaluation biases, potentially jeopardizing their internal validity and decreasing the degree of BP reduction we can expect to be achieved. Furthermore, the evaluation of the BP effect of renal denervation was mainly based on office BP measurement, a primary outcome that is subjected to observer bias. As expected, the BP-lowering effects of renal denervation, as assessed by ambulatory BP monitoring in few patients were smaller than those evaluated by office BP measurement. Finally, the external validity of the studies is also limited because they included a small sample of highly selected patients (mainly obese, Caucasian patients with resistant hypertension despite treatment with ?5 antihypertensive drugs, a glomerular filtration rate >45 ml/ min and a suitable renal artery anatomy) making it difficult to extrapolate the results to the general population of patients with resistant hypertension. In this context, there are strong arguments against the widespread and uncontrolled use of this procedure in routine practice: an unknown benefit/risk ratio, inconsistency and unpredictability of the BP response, absence of markers of primary success of the procedure, absence of cost-effectiveness evaluation, higher risk when renal denervation is performed by interventionalists less skilled at patient selection and performance of the procedure. The best way to ensure the rigorous follow-up of patients after renal denervation would therefore be to include them in clinical trials or international registries. L’auteur n’a pas transmis de conflit d’intérêt concernant les données diffusées dans cette vidéo ou publiées dans la référence citée. 9th Global Cardiovascular Clinical Trialists Forum • Paris 2012 HYPERTENSION TRIALIST WORKSHOP: AUTONOMIC MODULATION THERAPY Chairpersons: George BAKRIS, Chicago, USA - Sverre E. KJELDSEN, Oslo, NOR Resistant hypertension is usually defined as uncontrolled hypertension despite the intake of at least 3 antihypertensive drugs in full doses including a diuretic. Most investigators would also claim that this also implies 24-hours systolic blood pressure remaining above 135 (or 140) mmHg. Over the years some evidence has accumulated that raised sympathetic nervous system activity is involved in the pathogenesis of hypertension and particularly so in more severe hypertension. - Ablation of the renal nerves located in the adventitia of renal arteries has emerged as a novel treatment modality and a catheter manufactured by Adrian/Medtronic has been CE approved in Europe based on one RCT (SYMPLICITY -2). A much larger trial is ongoing (SIMPICITY 3). Several other producers have applied for approval. - CVRx have developed Barostim based on carotid baroreceptors stimulation and have gathered some early experience with encouraging results that led to CE mark. - These techniques have rapidly been taken up in several countries including in a large number of centers in Germany. - Beyond resistant hypertension, various devices providing autonomic modulation therapy are entering the clinical development stages also in heart failure, CKD and diabetes. - Vagal stimulation developed by Medtronic (Biocontrol) and Boston Scientific are being tested in the INOVATE-HF and NECTAR-HF respectively in systolic heart failure. - Spinal Cord stimulation is considered by many in small proof of concept trials (St Jude SCS HEART) (Medtronic DEFEAT-HF) - Understanding the differences in the clinical and regulatory environments in the United States and Europe helps explain why much early device testing takes place outside of the United States, and why the introduction of new devices into clinical practice is usually significantly delayed in the United States when compared with Europe. - Both phenomena are direct results of inherent differences in the criteria for approval and the process required to obtain approval. In particular, the European CE Mark process requires demonstration of safety only (and not efficacy) and relies heavily on non-governmental notified bodies to regulate the approval and post-approval process. In contrast, the approval of a new high-risk device in the United States requires demonstration of both safety and efficacy and is more highly regulated by a central governmental agency (CDRH/FDA). The aim of this workshop is to assemble primary investigators of a number of important ongoing trials and discuss preliminary results, strengths and limitations of the current trials, efficacy and safety endpoint related issues, as well as issues related to optimal trial design, approvability and implementation into daily clinical practice. Device companies: CVRx, Medtronic, St. Jude, Marquette, Boston Scientific, Vessix Vascular, ReCor Medical, Adrian, Biosense, Maya Medical. Réalisation, production : Canal U/3S et CERIMES Keyword : Cardiovascular Clinical Trialists, Paris, 2012, Cardiovascular prevention, cardiovascular pharmacology, modulation therapy

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