Name Rosa de Jager
Date defended June 27, 2017
(Co-) Supervisors Prof. Dr M.L. Bots, Prof. Dr M.C. Verhaar, Dr P.J. Blankestijn
Title of thesis Renal denervation: under pressure?

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Thesis summary
Worldwide, 871 million people suffers from hypertension (an office systolic blood pressure (BP) of ≥140 and/or diastolic BP ≥90 mmHg). Only 35% of the patients known with hypertension reaches guideline targets. The remaining 65% percent is defined as having resistant hypertension, in other words, not responding on pharmacological treatment. Experimental and clinical studies suggested that an overactivated sympathetic nervous system together with the kidneys play an important role in the development of resistant hypertension. Recently, percutaneous renal denervation (RDN) has been introduced as new therapeutic option for resistant hypertension. The procedure itself is comparable with percutaneous transluminal angioplasty. RDN means literally disruption of the renal nerves, which is performed with radiofrequency energy. The hypothesis is that RDN lowers BP in resistant hypertensive patients. Aims The primary aim of this thesis is to determine the BP lowering effect of percutaneous RDN. Secondary aim was to explore which factors influence the effect of RDN on BP. Methods To answer our primary aim, we conducted an open-label randomized controlled multicenter trial in the Netherlands from 2013 till 2016 (the SYMPATHY trial, number: NCT01850901). Our primary endpoint was the BP lowering effect of RDN compared to usual care six months after treatment in patients with resistant hypertension. Furthermore, two new secondary objectives were added: 1) to study the adherence to BP lowering drugs at baseline and 2) to study the change in adherence during the conduct of the study and the effect this change had on the observed change in BP after RDN. Medication adherence was objectively assessed with stored blood, sampled at baseline and follow-up, without knowledge of patients and physicians. We collected patient characteristics, biochemical parameters and peri-procedural complications during follow-up. With these data and the data of our Dutch RDN registry, we were able to answer which factors influence the BP lowering effect of RDN. Results In SYMPATHY, one hundred thirty-nine patients were randomized (95 RDN). Our primary analysis showed no beneficial effect of RDN on daytime systolic BP, compared to usual care alone after six months (mean difference of 2 [-6.1 to 10.2] mmHg in favor of control group). Our data suggested that RDN was a safe procedure. Sixty-eight percent of the patients was (partially) non-adherent to their prescribed BP lowering drugs (N=67). The more pills were prescribed, the less pills were detected in blood. The level of adherence influenced the magnitude and direction of the effect of RDN on BP. Women with a history of hypertensive disorders of pregnancy (HDP) were highly prevalent among the resistant hypertensive population and were likely to have a better response after RDN. Conclusions RDN was not superior to usual care to lower BP in apparent resistant hypertensive patients. Poor adherence was common in patients with apparent resistant hypertension. Medication changes considerably affected the magnitude and direction of the RDN effect on BP. Resistant hypertensive women with previous HDP might have a larger decline in BP after RDN than women without previous HDP.