Renal Denervation: Is Reality Meeting Expectations?
Savard S, Frank M, Bobrie G, Plouin PF, Sapoval M, Azizi M. Eligibility for renal denervation in patients with resistant hypertension: when enthusiasm meets reality in real-life patients. J Am Coll Cardiol. 2012;60:2422-2424.
Michel Azizi, MD, PhD, is Professor of Vascular Medicine at Paris Descartes University and Head of the Clinical Investigation Center and Cardiovascular Consultant at the Hôpital Européen Georges Pompidou of Paris, France. Prof. Azizi is a member of the Clinical Research Commission of INSERM (Institut National de la Santé et de la Recherche Médicale). His main research interests include resistant hypertension and the physiology, genetics, and pharmacology of the renin-angiotensin-aldosterone system. He received the Jean Hamburger Prize for Medical Research in 2007 and the Peter van Zwieten Award of the European Society of Hypertension (ESH) in 2011.
Prof. Azizi is a member of the French Society of Cardiology, the ESH, and the European Society of Cardiology. He has published more than 120 papers in peer-reviewed journals. He has been an investigator on several trials of renal denervation, including the Symplicity HTN-2 trial and the ongoing REDUCE-HTN trial. He is co-principal investigator on the French DENER-HTN trial.
"Resistant hypertension" is usually defined as blood pressure that remains above goal despite lifestyle measures and concurrent use of 3 antihypertensive agents of different classes, prescribed at optimal doses, including a diuretic. Estimates of the prevalence of patients with truly resistant hypertension based on these criteria vary widely. Overall, observational studies and clinical trials suggest that 8%-30% of treated hypertension patients have resistant hypertension.
Until now, treatment of real resistant hypertension has been focused on pharmacologically blocking all possible mechanisms for blood pressure elevation, especially by using spironolactone at a low dose (25-50 mg once daily) as fourth-line therapy. In recent years, however, percutaneous catheter-based renal artery ablation (renal denervation) has emerged as a new approach to achieving blood pressure reduction in these patients. The rationale for its clinical use is based on the role of sympathetic overactivity in the maintenance of high blood pressure, especially in patients with resistant hypertension.
Therapeutic benefit in terms of office blood pressure reduction was demonstrated with the Symplicity renal denervation system (Medtronic, Minneapolis, Minnesota) in a proof-of-principle study (Symplicity HTN-1), followed by a small open-label randomized efficacy study (Symplicity HTN-2) that included about 50 patients per group. Blood pressure reduction achieved on ambulatory monitoring was less than in the office. The Symplicity system was launched in Europe in 2010 and is also currently available in Asia, Africa, Australia, and Canada. No renal denervation system has yet been approved in the United States.
Since the publication of the Symplicity HTN-2 trial in 2010, increasing excitement from the press and at medical conferences has been generated about the future of renal denervation systems. The Cleveland Clinic nominated renal denervation as the number-1 healthcare innovation of 2012. Four different new systems have become available in Europe since the launch of the Symplicity system, and many others are under development worldwide.
Global predictions of the numbers of patients who might benefit from renal denervation vary as widely as the estimates of the true rate of resistant hypertension. Up to 12 million potential patients have been suggested for Europe and North America. Several commentators have urged a cautious approach, however, given the limited evidence (a single open-label trial); the less impressive blood pressure-lowering effect when assessed by ambulatory monitoring; the absence of long-term efficacy and safety data; the emergence of adverse effects, such as de novo renal artery stenoses of unknown incidence, and whether the blood pressure reductions achieved with renal denervation translate into reductions in cardiovascular or renal events.
The increasing use of renal denervation led the ESH to issue a position paper reviewing clinical evidence and setting out eligibility criteria for the procedure. The authors of the paper also cautioned that until further clinical data become available, renal denervation should be used only in patients with resistant hypertension who have been carefully selected at specialist hypertension centers.
To try to identify the true proportion of hypertensive patients who might benefit from renal denervation with the Symplicity system in "real-life conditions," Prof. Azizi and colleagues retrospectively reviewed the medical records of all consecutive patients hospitalized for at least 1 day during 2011 at the Vascular Medicine and Hypertension Unit of the Hôpital Européen Georges Pompidou, Paris. Of a total of 3067 patients referred to the unit during that year, 1034 fulfilled the criteria for the analysis (age 18-79 years, hypertensive, complete in-hospital work-up, and hospitalized ≥1 day). Two hundred of these patients met the definition of resistant hypertension according to ESH criteria (office systolic/diastolic blood pressure ≥140 mm Hg and/or 90 mm Hg [or ≥130 mm Hg and/or 80 mm Hg in patients with diabetes] despite treatment with at least 3 drugs, including a diuretic, prescribed at the maximum tolerated dose).
After 113 patients had been excluded because of secondary hypertension (ie, hypertension associated with an underlying, identifiable cause), only 87 (43.5%) were identified as having essential resistant hypertension. In this group, Prof. Azizi and colleagues applied the ESH eligibility criteria for renal denervation, including systolic blood pressure ≥160 mm Hg or ≥150 mm Hg in patients with type 2 diabetes despite use of 3 or more antihypertensive drugs, including a diuretic, with out-of-office blood pressure measurements (daytime ambulatory or home) ≥135 mm Hg and/or 85 mm Hg, estimated glomerular filtration rate ≥45 mL/min per 1.73 m, and suitable renal artery anatomy. On the basis of these criteria, only 15 patients (17.2% of those with resistant hypertension) seemed to be fully eligible for renal denervation. This finding implies that the procedure is limited to "a highly selected fraction of patients with resistant hypertension, even in a specialist hypertension unit," the investigators concluded.
Prof. Azizi spoke with Linda Brookes for Medscape Cardiology about the study, and the potential for and problems facing the future application of renal denervation in resistant hypertension.
A Best Evidence Interview With Michel Azizi, MD, PhD
The Study
Savard S, Frank M, Bobrie G, Plouin PF, Sapoval M, Azizi M. Eligibility for renal denervation in patients with resistant hypertension: when enthusiasm meets reality in real-life patients. J Am Coll Cardiol. 2012;60:2422-2424.
About the Interviewee
Michel Azizi, MD, PhD, is Professor of Vascular Medicine at Paris Descartes University and Head of the Clinical Investigation Center and Cardiovascular Consultant at the Hôpital Européen Georges Pompidou of Paris, France. Prof. Azizi is a member of the Clinical Research Commission of INSERM (Institut National de la Santé et de la Recherche Médicale). His main research interests include resistant hypertension and the physiology, genetics, and pharmacology of the renin-angiotensin-aldosterone system. He received the Jean Hamburger Prize for Medical Research in 2007 and the Peter van Zwieten Award of the European Society of Hypertension (ESH) in 2011.
Prof. Azizi is a member of the French Society of Cardiology, the ESH, and the European Society of Cardiology. He has published more than 120 papers in peer-reviewed journals. He has been an investigator on several trials of renal denervation, including the Symplicity HTN-2 trial and the ongoing REDUCE-HTN trial. He is co-principal investigator on the French DENER-HTN trial.
Background to the Interview
"Resistant hypertension" is usually defined as blood pressure that remains above goal despite lifestyle measures and concurrent use of 3 antihypertensive agents of different classes, prescribed at optimal doses, including a diuretic. Estimates of the prevalence of patients with truly resistant hypertension based on these criteria vary widely. Overall, observational studies and clinical trials suggest that 8%-30% of treated hypertension patients have resistant hypertension.
Until now, treatment of real resistant hypertension has been focused on pharmacologically blocking all possible mechanisms for blood pressure elevation, especially by using spironolactone at a low dose (25-50 mg once daily) as fourth-line therapy. In recent years, however, percutaneous catheter-based renal artery ablation (renal denervation) has emerged as a new approach to achieving blood pressure reduction in these patients. The rationale for its clinical use is based on the role of sympathetic overactivity in the maintenance of high blood pressure, especially in patients with resistant hypertension.
Therapeutic benefit in terms of office blood pressure reduction was demonstrated with the Symplicity renal denervation system (Medtronic, Minneapolis, Minnesota) in a proof-of-principle study (Symplicity HTN-1), followed by a small open-label randomized efficacy study (Symplicity HTN-2) that included about 50 patients per group. Blood pressure reduction achieved on ambulatory monitoring was less than in the office. The Symplicity system was launched in Europe in 2010 and is also currently available in Asia, Africa, Australia, and Canada. No renal denervation system has yet been approved in the United States.
Since the publication of the Symplicity HTN-2 trial in 2010, increasing excitement from the press and at medical conferences has been generated about the future of renal denervation systems. The Cleveland Clinic nominated renal denervation as the number-1 healthcare innovation of 2012. Four different new systems have become available in Europe since the launch of the Symplicity system, and many others are under development worldwide.
Global predictions of the numbers of patients who might benefit from renal denervation vary as widely as the estimates of the true rate of resistant hypertension. Up to 12 million potential patients have been suggested for Europe and North America. Several commentators have urged a cautious approach, however, given the limited evidence (a single open-label trial); the less impressive blood pressure-lowering effect when assessed by ambulatory monitoring; the absence of long-term efficacy and safety data; the emergence of adverse effects, such as de novo renal artery stenoses of unknown incidence, and whether the blood pressure reductions achieved with renal denervation translate into reductions in cardiovascular or renal events.
The increasing use of renal denervation led the ESH to issue a position paper reviewing clinical evidence and setting out eligibility criteria for the procedure. The authors of the paper also cautioned that until further clinical data become available, renal denervation should be used only in patients with resistant hypertension who have been carefully selected at specialist hypertension centers.
To try to identify the true proportion of hypertensive patients who might benefit from renal denervation with the Symplicity system in "real-life conditions," Prof. Azizi and colleagues retrospectively reviewed the medical records of all consecutive patients hospitalized for at least 1 day during 2011 at the Vascular Medicine and Hypertension Unit of the Hôpital Européen Georges Pompidou, Paris. Of a total of 3067 patients referred to the unit during that year, 1034 fulfilled the criteria for the analysis (age 18-79 years, hypertensive, complete in-hospital work-up, and hospitalized ≥1 day). Two hundred of these patients met the definition of resistant hypertension according to ESH criteria (office systolic/diastolic blood pressure ≥140 mm Hg and/or 90 mm Hg [or ≥130 mm Hg and/or 80 mm Hg in patients with diabetes] despite treatment with at least 3 drugs, including a diuretic, prescribed at the maximum tolerated dose).
After 113 patients had been excluded because of secondary hypertension (ie, hypertension associated with an underlying, identifiable cause), only 87 (43.5%) were identified as having essential resistant hypertension. In this group, Prof. Azizi and colleagues applied the ESH eligibility criteria for renal denervation, including systolic blood pressure ≥160 mm Hg or ≥150 mm Hg in patients with type 2 diabetes despite use of 3 or more antihypertensive drugs, including a diuretic, with out-of-office blood pressure measurements (daytime ambulatory or home) ≥135 mm Hg and/or 85 mm Hg, estimated glomerular filtration rate ≥45 mL/min per 1.73 m, and suitable renal artery anatomy. On the basis of these criteria, only 15 patients (17.2% of those with resistant hypertension) seemed to be fully eligible for renal denervation. This finding implies that the procedure is limited to "a highly selected fraction of patients with resistant hypertension, even in a specialist hypertension unit," the investigators concluded.
Prof. Azizi spoke with Linda Brookes for Medscape Cardiology about the study, and the potential for and problems facing the future application of renal denervation in resistant hypertension.
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