Catheter-Based Renal Denervation for Resistant Hypertension
Catheter-Based Renal Denervation for Resistant Hypertension
Aim. The aim of this study was to determine long-term results of renal artery denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study.
Methods. SYMPLICITY HTN-2 randomized 106 subjects with treatment-resistant hypertension to renal denervation or medical therapy alone. At 6 months, 37 control subjects crossed over to renal denervation. Office blood pressure measurements, antihypertensive medication use, and safety events were followed every 6 months through 3 years.
Results. Follow-up was available at 36 months in 40 of 52 subjects in the initial renal denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal denervation at 6 months. Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg (95% CI: −40, −27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95% CI: −16, −10, P < 0.01). The systolic and diastolic blood pressure reduction at 36 months for the initial renal denervation group was −33 mmHg (95% CI: −40, −25, P < 0.01) and −14 mmHg (95% CI: −17, −10, P < 0.01), respectively. Procedural complications included one haematoma, and one renal artery dissection before energy delivery that was treated successfully. Later complications included two cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and three deaths.
Conclusion. Renal denervation resulted in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe, treatment-resistant hypertension without serious safety concerns.
The prevalence of hypertension is increasing worldwide at alarming rates. Furthermore, the prevalence of uncontrolled hypertension is also increasing, in spite of advances in pharmacotherapy. Patients with treatment-resistant hypertension (blood pressure ≥140/90 mmHg despite ≥3 antihypertensive medications, including a diuretic) often have other risk factors for cardiovascular disease and consequently are at even greater risk for end-organ damage and cardiovascular morbidities. When confounding causes, such as white-coat hypertension, non-adherence to drug therapy, and inappropriate drug selection or dosing, are eliminated, the estimated proportion of patients with treatment-resistant hypertension ranges from 5 to 16%.
Renal sympathetic outflow is commonly overactive in patients with essential hypertension; this has been demonstrated by measurements of norepinephrine spillover from renal sympathetic nerves. Pre-clinical work revealed that surgical sectioning of the renal nerves in experimental animal models of hypertension lowers blood pressure or can prevent development of hypertension.
Percutaneous catheter-based renal denervation (RDN) using the Symplicity™ Renal Denervation System (Medtronic, Inc., Santa Rosa, CA, USA) involves the application of low-power (~8 W) radiofrequency energy to the main renal arteries in a helical pattern of ablations (four to six per artery). The renal artery nerves passing to and from the kidneys transit in the adventitia of the renal artery or just beyond and are therefore within reach of energy delivery. The Symplicity generator uses a proprietary algorithm to monitor and control temperature, impedance, and power output to assure safe delivery of energy to each site. The SYMPLICITY HTN-1 proof-of-principle trial demonstrated the feasibility of this procedure and showed that subjects with severe, treatment-resistant hypertension experienced a significant reduction in blood pressure that was sustained over at least 3 years (−32/−14 mmHg at 36 months, P < 0.01).
The SYMPLICITY HTN-2 randomized clinical trial compared the safety and effectiveness of RDN plus medical management to medical management alone (control group) in subjects with severe treatment-resistant hypertension. At 6-month post-randomization, there was a significant decrease from baseline blood pressure for the initial RDN group (n = 49; −32/−12 mmHg, P < 0.0001) and no change in blood pressure from baseline in the control group (n = 51). No serious device or procedure-related adverse events were reported at the 6-month primary endpoint.
The SYMPLICITY HTN-2 trial allowed control subjects to crossover to receive RDN after the initial 6-month primary endpoint evaluation. We now report 36-month follow-up of the initially denervated subjects and 30-month follow-up of the control subjects who crossed over to RDN at 6 months.
Abstract and Introduction
Abstract
Aim. The aim of this study was to determine long-term results of renal artery denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study.
Methods. SYMPLICITY HTN-2 randomized 106 subjects with treatment-resistant hypertension to renal denervation or medical therapy alone. At 6 months, 37 control subjects crossed over to renal denervation. Office blood pressure measurements, antihypertensive medication use, and safety events were followed every 6 months through 3 years.
Results. Follow-up was available at 36 months in 40 of 52 subjects in the initial renal denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal denervation at 6 months. Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg (95% CI: −40, −27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95% CI: −16, −10, P < 0.01). The systolic and diastolic blood pressure reduction at 36 months for the initial renal denervation group was −33 mmHg (95% CI: −40, −25, P < 0.01) and −14 mmHg (95% CI: −17, −10, P < 0.01), respectively. Procedural complications included one haematoma, and one renal artery dissection before energy delivery that was treated successfully. Later complications included two cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and three deaths.
Conclusion. Renal denervation resulted in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe, treatment-resistant hypertension without serious safety concerns.
Introduction
The prevalence of hypertension is increasing worldwide at alarming rates. Furthermore, the prevalence of uncontrolled hypertension is also increasing, in spite of advances in pharmacotherapy. Patients with treatment-resistant hypertension (blood pressure ≥140/90 mmHg despite ≥3 antihypertensive medications, including a diuretic) often have other risk factors for cardiovascular disease and consequently are at even greater risk for end-organ damage and cardiovascular morbidities. When confounding causes, such as white-coat hypertension, non-adherence to drug therapy, and inappropriate drug selection or dosing, are eliminated, the estimated proportion of patients with treatment-resistant hypertension ranges from 5 to 16%.
Renal sympathetic outflow is commonly overactive in patients with essential hypertension; this has been demonstrated by measurements of norepinephrine spillover from renal sympathetic nerves. Pre-clinical work revealed that surgical sectioning of the renal nerves in experimental animal models of hypertension lowers blood pressure or can prevent development of hypertension.
Percutaneous catheter-based renal denervation (RDN) using the Symplicity™ Renal Denervation System (Medtronic, Inc., Santa Rosa, CA, USA) involves the application of low-power (~8 W) radiofrequency energy to the main renal arteries in a helical pattern of ablations (four to six per artery). The renal artery nerves passing to and from the kidneys transit in the adventitia of the renal artery or just beyond and are therefore within reach of energy delivery. The Symplicity generator uses a proprietary algorithm to monitor and control temperature, impedance, and power output to assure safe delivery of energy to each site. The SYMPLICITY HTN-1 proof-of-principle trial demonstrated the feasibility of this procedure and showed that subjects with severe, treatment-resistant hypertension experienced a significant reduction in blood pressure that was sustained over at least 3 years (−32/−14 mmHg at 36 months, P < 0.01).
The SYMPLICITY HTN-2 randomized clinical trial compared the safety and effectiveness of RDN plus medical management to medical management alone (control group) in subjects with severe treatment-resistant hypertension. At 6-month post-randomization, there was a significant decrease from baseline blood pressure for the initial RDN group (n = 49; −32/−12 mmHg, P < 0.0001) and no change in blood pressure from baseline in the control group (n = 51). No serious device or procedure-related adverse events were reported at the 6-month primary endpoint.
The SYMPLICITY HTN-2 trial allowed control subjects to crossover to receive RDN after the initial 6-month primary endpoint evaluation. We now report 36-month follow-up of the initially denervated subjects and 30-month follow-up of the control subjects who crossed over to RDN at 6 months.
Source...