Archives of Cardiovascular Disease (2014) 107, 421—423
Available online at
ScienceDirect www.sciencedirect.com
SCIENTIFIC EDITORIAL
Renal denervation in hypertension: Simplicity, or complexity? Dénervation rénale dans l’hypertension artérielle : complexité après « Simplicity » Pierre Lantelme a,∗,b,c, Pierre-Yves Courand a,b,c, Giampiero Bricca a,b,c a
Fédération de cardiologie, European Society of Hypertension Excellence Centre, hôpital de la Croix-Rousse, hospices civils de Lyon, 103, Grande Rue de la Croix-Rousse, 69004 Lyon, France b Génomique fonctionnelle de l’hypertension artérielle, EA 4173, université Claude-Bernard Lyon 1, 69100 Villeurbanne, France c Hôpital Nord-Ouest, 69400 Villefranche-sur-Saône, France Received 18 June 2014; accepted 19 June 2014 Available online 13 August 2014
KEYWORDS Renal denervation; Hypertension; Ablation; Sympathetic nervous system
MOTS CLÉS Denervation rénale ; Hypertension ; Ablation ; Système nerveux sympathique
∗
Renal denervation for the treatment of resistant hypertension has prompted tremendous interest in the medical community, from hypertension specialists to interventional cardiologists. At the end of 2010, the amazing results of the Symplicity HTN-1 and -2 trials, showing a huge reduction in office blood pressure (BP) in patients with uncontrolled hypertension despite treatment with more than five medications on average, led many physicians to ‘dream’ that this non-pharmacological technique could be used in the future in less severe hypertension [1,2]. The ‘market’ is potentially huge, and many companies set up their own devices to perform renal denervation; numerous meetings and symposia were held, and many interventional cardiologists were ready to ‘denervate’ arteries. Everyone predicted a rapid rise in the number of patients treated with this technique. But, three years later, not as many patients as anticipated have been treated, at least not in France. This was probably due to economic considerations because the device was not reimbursed, but also to the position of the French Society of Hypertension, which was reluctant to disseminate this technique too rapidly in view of the limited scientific evidence. A consensus document on renal denervation was published in 2012 that delineated the mandatory steps that must be fulfilled, based on available data, before proposing this technique to a patient [3].
Corresponding author. Service de cardiologie, hôpital de la Croix-Rousse, 103, Grande Rue de la Croix-Rousse, 69004, Lyon, France. E-mail address: [email protected] (P. Lantelme).
http://dx.doi.org/10.1016/j.acvd.2014.06.006 1875-2136/© 2014 Elsevier Masson SAS. All rights reserved.
422 Early in this process, emphasis was placed on the need to perform renal denervation in specialized units trained in the management of hypertension, and not by ‘new comers’ unfamiliar with this specific area. Some highly specialized centres in France belonging to the European Hypertension Excellence Centre network fulfil such characteristics and were therefore positioned to become such centres. Another aspect that limits the number of procedures is the complexity of the selection of patients and the low number of indications, which prevented centres that did not have a well-organized network for the management of difficult hypertension before the emergence of renal denervation from recruiting sufficient cases. In parallel, some teams or protocols encouraged less rigorous use of renal denervation, for example, when the anatomy is less favourable (e.g. in a polar artery) or when renal function is altered. So far the results have been rather disappointing [4,5]. The past few weeks have been extremely harsh for renal denervation, first with the publication of the Symplicity HTN-3 results [6]. This double-blind randomized trial, required by the Food and Drug Administration before the technique could be introduced into the United States, was characterized primarily by the fact that the control group underwent a sham procedure; therefore all patients, treated or untreated, had an invasive procedure and were, along with their physicians, unaware of whether they had had a denervation. The results, obtained in more than 500 patients, were extremely disappointing because no significant BP difference between the active and the control arm was observed at the end of follow-up. At this stage, many investigators and opinion leaders claimed that the technique of renal denervation was ‘dead’. A few days ago, at the European Hypertension Meeting in Athens, the results of the French DENER-HTN study were presented [7]. This study was conducted in the network of the French Hypertension Excellence Centres and its major goal was to determine the effect of renal denervation on top of optimal medical therapy. The novel and important aspect of this study, in which lies its major strength, was the level of standardization of the treatment, with precise guidance given for the molecules and the doses at each step. Although not as impressive as the results of the Symplicity HTN-1 and -2 trial, the results were significant, with a reduction of daytime and nighttime systolic BP 6 mmHg greater than in the control arm despite the same level of medication (again in terms of molecules and doses). More importantly, it was the combination of a rigorously adjusted treatment and renal denervation that proved effective in improving BP control in these patients, emphasizing the importance of the ‘classic’ pharmacological approach of managing treatment, along with the more ‘fashionable’ technical approach of renal denervation. Why were these two recent trials so different in terms of their results and the benefit of the technique? The major differences are summarized briefly in Table 1 below. From our perspective the most significant difference is not the sham procedure, missing in the French study, but the fact that in DENER-HTN the patients were managed by specialized centres at every step: inclusion, work-up, procedure, and follow-up. Why is the absence of a sham procedure not so critical? We are dealing with patients with severe, resistant hypertension who are on maximal medical
P. Lantelme et al. Table 1 Comparison of the Symplicity HTN-3 and DENER-HTN studies.
Sham procedure Standardized treatment Specialized centres involved Trained operators Use of spironolactone Use of ambulatory blood pressure
Simplicity HTN-3
DENER-HTN
Yes No
No Yes
No
Yes
No (in >50% of cases)
Available online at
ScienceDirect www.sciencedirect.com
SCIENTIFIC EDITORIAL
Renal denervation in hypertension: Simplicity, or complexity? Dénervation rénale dans l’hypertension artérielle : complexité après « Simplicity » Pierre Lantelme a,∗,b,c, Pierre-Yves Courand a,b,c, Giampiero Bricca a,b,c a
Fédération de cardiologie, European Society of Hypertension Excellence Centre, hôpital de la Croix-Rousse, hospices civils de Lyon, 103, Grande Rue de la Croix-Rousse, 69004 Lyon, France b Génomique fonctionnelle de l’hypertension artérielle, EA 4173, université Claude-Bernard Lyon 1, 69100 Villeurbanne, France c Hôpital Nord-Ouest, 69400 Villefranche-sur-Saône, France Received 18 June 2014; accepted 19 June 2014 Available online 13 August 2014
KEYWORDS Renal denervation; Hypertension; Ablation; Sympathetic nervous system
MOTS CLÉS Denervation rénale ; Hypertension ; Ablation ; Système nerveux sympathique
∗
Renal denervation for the treatment of resistant hypertension has prompted tremendous interest in the medical community, from hypertension specialists to interventional cardiologists. At the end of 2010, the amazing results of the Symplicity HTN-1 and -2 trials, showing a huge reduction in office blood pressure (BP) in patients with uncontrolled hypertension despite treatment with more than five medications on average, led many physicians to ‘dream’ that this non-pharmacological technique could be used in the future in less severe hypertension [1,2]. The ‘market’ is potentially huge, and many companies set up their own devices to perform renal denervation; numerous meetings and symposia were held, and many interventional cardiologists were ready to ‘denervate’ arteries. Everyone predicted a rapid rise in the number of patients treated with this technique. But, three years later, not as many patients as anticipated have been treated, at least not in France. This was probably due to economic considerations because the device was not reimbursed, but also to the position of the French Society of Hypertension, which was reluctant to disseminate this technique too rapidly in view of the limited scientific evidence. A consensus document on renal denervation was published in 2012 that delineated the mandatory steps that must be fulfilled, based on available data, before proposing this technique to a patient [3].
Corresponding author. Service de cardiologie, hôpital de la Croix-Rousse, 103, Grande Rue de la Croix-Rousse, 69004, Lyon, France. E-mail address: [email protected] (P. Lantelme).
http://dx.doi.org/10.1016/j.acvd.2014.06.006 1875-2136/© 2014 Elsevier Masson SAS. All rights reserved.
422 Early in this process, emphasis was placed on the need to perform renal denervation in specialized units trained in the management of hypertension, and not by ‘new comers’ unfamiliar with this specific area. Some highly specialized centres in France belonging to the European Hypertension Excellence Centre network fulfil such characteristics and were therefore positioned to become such centres. Another aspect that limits the number of procedures is the complexity of the selection of patients and the low number of indications, which prevented centres that did not have a well-organized network for the management of difficult hypertension before the emergence of renal denervation from recruiting sufficient cases. In parallel, some teams or protocols encouraged less rigorous use of renal denervation, for example, when the anatomy is less favourable (e.g. in a polar artery) or when renal function is altered. So far the results have been rather disappointing [4,5]. The past few weeks have been extremely harsh for renal denervation, first with the publication of the Symplicity HTN-3 results [6]. This double-blind randomized trial, required by the Food and Drug Administration before the technique could be introduced into the United States, was characterized primarily by the fact that the control group underwent a sham procedure; therefore all patients, treated or untreated, had an invasive procedure and were, along with their physicians, unaware of whether they had had a denervation. The results, obtained in more than 500 patients, were extremely disappointing because no significant BP difference between the active and the control arm was observed at the end of follow-up. At this stage, many investigators and opinion leaders claimed that the technique of renal denervation was ‘dead’. A few days ago, at the European Hypertension Meeting in Athens, the results of the French DENER-HTN study were presented [7]. This study was conducted in the network of the French Hypertension Excellence Centres and its major goal was to determine the effect of renal denervation on top of optimal medical therapy. The novel and important aspect of this study, in which lies its major strength, was the level of standardization of the treatment, with precise guidance given for the molecules and the doses at each step. Although not as impressive as the results of the Symplicity HTN-1 and -2 trial, the results were significant, with a reduction of daytime and nighttime systolic BP 6 mmHg greater than in the control arm despite the same level of medication (again in terms of molecules and doses). More importantly, it was the combination of a rigorously adjusted treatment and renal denervation that proved effective in improving BP control in these patients, emphasizing the importance of the ‘classic’ pharmacological approach of managing treatment, along with the more ‘fashionable’ technical approach of renal denervation. Why were these two recent trials so different in terms of their results and the benefit of the technique? The major differences are summarized briefly in Table 1 below. From our perspective the most significant difference is not the sham procedure, missing in the French study, but the fact that in DENER-HTN the patients were managed by specialized centres at every step: inclusion, work-up, procedure, and follow-up. Why is the absence of a sham procedure not so critical? We are dealing with patients with severe, resistant hypertension who are on maximal medical
P. Lantelme et al. Table 1 Comparison of the Symplicity HTN-3 and DENER-HTN studies.
Sham procedure Standardized treatment Specialized centres involved Trained operators Use of spironolactone Use of ambulatory blood pressure
Simplicity HTN-3
DENER-HTN
Yes No
No Yes
No
Yes
No (in >50% of cases)
