Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial

Michel Azizi; Helena Pereira; Idir Hamdidouche; Philippe Gosse; Matthieu Monge; Guillaume Bobrie; Pascal Delsart; Claire Mounier-Véhier; Pierre-Yves Courand; Pierre Lantelme; Thierry Denolle; Caroline Dourmap-Collas; Xavier Girerd; Jean Michel Halimi; Faiez Zannad; Olivier Ormezzano; Bernard Vaïsse; Daniel Herpin; Jean Ribstein; Bernard Chamontin; Jean-Jacques Mourad; Emile Ferrari; Pierre-François Plouin; Vincent Jullien; Marc Sapoval; Gilles Chatellier; DENERHTN Investigators

doi:10.1161/CIRCULATIONAHA.116.022922

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial

Circulation. 2016 Sep 20;134(12):847-57. doi: 10.1161/CIRCULATIONAHA.116.022922. Epub 2016 Aug 30.

Authors

Michel Azizi¹, Helena Pereira², Idir Hamdidouche², Philippe Gosse², Matthieu Monge², Guillaume Bobrie², Pascal Delsart², Claire Mounier-Véhier², Pierre-Yves Courand², Pierre Lantelme², Thierry Denolle², Caroline Dourmap-Collas², Xavier Girerd², Jean Michel Halimi², Faiez Zannad², Olivier Ormezzano², Bernard Vaïsse², Daniel Herpin², Jean Ribstein², Bernard Chamontin², Jean-Jacques Mourad², Emile Ferrari², Pierre-François Plouin², Vincent Jullien², Marc Sapoval², Gilles Chatellier²; DENERHTN Investigators

Collaborators

DENERHTN Investigators:
L Amar, A Lorthioir, J-Y Pagny, G Claisse, M Midulla, R Dauphin, J P Fauvel, O Rouvière, A Cremer, N Grenier, Y Lebras, H Trillaud, J F Heautot, A Larralde, F Paillard, P Cluzel, D Rosenbaum, D Alison, M Claudon, B Popovic, P Rossignol, J P Baguet, F Thony, J M Bartoli, J Drouineau, P Sosner, J P Tasu, S Velasco, H Vernhet-Kovacsik, B Bouhanick, H Rousseau, S Le Jeune, M Lopez-Sublet, L Bellmann, V Esnault, J P Baguet, H Vernhet-Kovacsik, I Durand-Zaleski, J P Beregi Chair, M Lièvre, A Persu

Affiliations

¹ From Paris-Descartes University, France (M.A., P.-F.P., V.J., M.S., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, France (M.A., G.B., P.-F.P.); INSERM, CIC1418, Paris, France (M.A., H.P., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Clinical Research Unit, France (H.P., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pharmacology, France (I.H., V.J.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Cardiology/Hypertension Department, France (P.G.); Institut Mutualiste Montsouris, Paris, France (M.M.); Centre Hospitalier Régional Universitaire de Lille, Hôpital Cardiologique, Médecine Vasculaire et HTA, France (P.D., C.M.-V.); Hôpital Croix-Rousse, Cardiology Department, European Society of Hypertension Excellence Centre, Hospices Civils de Lyon, and Université de Lyon, CREATIS UMR5220; INSERM U1044; INSA-Lyon; Université Claude Bernard Lyon 1; Hospices Civils de Lyon, France (P.-Y.C., P.L.); Hôpital Arthur Gardiner, Centre d'excellence en HTA Rennes-Dinard, France (T.D.); Centre Hospitalier Universitaire de Rennes, Service de Cardiologie et Maladies Vasculaires, France (C.D.-C.); Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié Salpétrière, France (X.G.); Hôpital Bretonneau, Tours, France (J.M.H.); CHU Nancy-Brabois, Nancy, France (F.Z.); CHU de Grenoble, France (O.O.); CHU de la Timone, Marseille, France (B.V.); CHU de Poitiers, Cardiologie, France (D.H.); CHRU Montpellier, France (J.R.); CHU Rangueil, Toulouse, France (B.C.); Hôpital Avicenne, Bobigny, France (J.-J.M.); Hôpital Pasteur, Nice, France (E.F.); INSERM, UMR 1129, Paris, France (V.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Vascular and Oncological Interventional Radiology Department, France (M.S.). michel.azizi@aphp.fr.
² From Paris-Descartes University, France (M.A., P.-F.P., V.J., M.S., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, France (M.A., G.B., P.-F.P.); INSERM, CIC1418, Paris, France (M.A., H.P., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Clinical Research Unit, France (H.P., G.C.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pharmacology, France (I.H., V.J.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Cardiology/Hypertension Department, France (P.G.); Institut Mutualiste Montsouris, Paris, France (M.M.); Centre Hospitalier Régional Universitaire de Lille, Hôpital Cardiologique, Médecine Vasculaire et HTA, France (P.D., C.M.-V.); Hôpital Croix-Rousse, Cardiology Department, European Society of Hypertension Excellence Centre, Hospices Civils de Lyon, and Université de Lyon, CREATIS UMR5220; INSERM U1044; INSA-Lyon; Université Claude Bernard Lyon 1; Hospices Civils de Lyon, France (P.-Y.C., P.L.); Hôpital Arthur Gardiner, Centre d'excellence en HTA Rennes-Dinard, France (T.D.); Centre Hospitalier Universitaire de Rennes, Service de Cardiologie et Maladies Vasculaires, France (C.D.-C.); Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié Salpétrière, France (X.G.); Hôpital Bretonneau, Tours, France (J.M.H.); CHU Nancy-Brabois, Nancy, France (F.Z.); CHU de Grenoble, France (O.O.); CHU de la Timone, Marseille, France (B.V.); CHU de Poitiers, Cardiologie, France (D.H.); CHRU Montpellier, France (J.R.); CHU Rangueil, Toulouse, France (B.C.); Hôpital Avicenne, Bobigny, France (J.-J.M.); Hôpital Pasteur, Nice, France (E.F.); INSERM, UMR 1129, Paris, France (V.J.); Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Vascular and Oncological Interventional Radiology Department, France (M.S.).

PMID: 27576780
DOI: 10.1161/CIRCULATIONAHA.116.022922

Abstract

Background: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control.

Methods: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients.

Results: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients.

Conclusions: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Keywords: ablation techniques; hypertension; kidney; medications; nervous system; sympathetic nervous system.

Publication types

Randomized Controlled Trial

MeSH terms

Antihypertensive Agents / therapeutic use*
Blood Pressure / drug effects*
Blood Pressure / physiology
Blood Pressure Determination / methods
Blood Pressure Monitoring, Ambulatory / methods
Female
Humans
Hypertension / drug therapy*
Hypertension / physiopathology
Kidney / drug effects*
Male
Medication Adherence
Middle Aged
Prospective Studies
Treatment Outcome

Substances

Antihypertensive Agents

Associated data

ClinicalTrials.gov/NCT01570777