Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial

Esler MD, Böhm M, Sievert H, et al.

Eur Heart J. 2014 Jul 7;35(26):1752-9

Background

Patients with treatment-resistant hypertension (blood pressure (BP) > 140/90 mmHg despite >3 antihypertensive medications, including a diuretic), often have other cardiovascular (CV) risk factors, thus putting them at further risk for end-organ damage and CV morbidities [1]. Estimates of truly treatment-resistant hypertension range from 5 to 16% [2-6].
Renal sympathetic outflow is often overactive in patients with essential hypertension, and it was initially shown in experimental animal models that surgical sectioning of the renal nerves lowered BP [7,8].
Percutaneous catheter-based renal denervation (RDN) involves the application of low-power (~8W) radiofrequency energy to the main renal arteries in a helical pattern of ablations [9,10]. The SYMPLICITY HTN-1 proof-of-principle trial showed the feasibility of the procedure, and patients with severe treatment resistant hypertension had sustained BP reduction for at least 3 years [11-13].
The SYMPLICITY HTN-2 was a randomised clinical that compared the safety and effectiveness of RND plus medical management to medical management alone (control group) in patients with severe treatment-resistant hypertension [14,15]. A significant decrease from baseline BP was seen 6 months after patients were randomised to RDN (-32/-12 mmHg, P<0.0001), while no significant change in BP was seen in the control group. The SYMPLICITY HTN-2 trial allowed control subjects to crossover to get RDN after the initial 6-month primary endpoint evaluation. This publication reports the 36-month follow-up of the initial-RDN group (n=40), and 30-month follow-up of the crossover subjects who received RDN 6 months later (n=30).

Main results

• Baseline SBP was 178+18 mmHg in the RDN group and 191+20 mmHg in the crossover group.
• SBP and DBP measurements were significantly lower than the pre-procedure measurement at all time points (6, 12, 24, 30 and 36 months). Reduction in BP did not diminish during follow-up. After 30 months, change in SBP was -34 mmHg (95%CI: -40 to -27, P<0.01) and change in DBP was -13 mmHg (95%CI: -16 to -10, P<0.01). Reduction of BP was similar for the original RDN and the crossover subjects.
• Response rate of achieving an SBP reduction of > 20 mmHg was similar for original RDN subjects (72%) and crossover subjects (70%).
• Heart rate was slowed following RDN, and the decrease persisted until 36 months (mean decrease 4 bpm (95%CI: -8 to -0.1, P=0.04).
• At 30 months, the mean number of antihypertensive medications was lowered from 5.1+1.4 at baseline to 4.8+1.5 (P=0.06) medications.
• Complications associated with the procedure included one haematoma, and one renal artery dissection before energy delivery, which could be treated successfully. Between 12 and 26 months after the procedure, five hypertensive events requiring hospitalisation and one case of mild transient acute renal failure were reported. Three deaths occurred during follow-up, which were considered unrelated to the device or therapy.

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Conclusion

This report adds long-term data on the safety and efficacy of RDN, by confirming the durability of the antihypertensive effects of RDN as shown in the earlier SYMPLICITY HTN-1 trial, in patients with severe treatment-resistant hypertension. The long-term effect was obtained without increasing medication, and without serious long-term safety concerns.
These data were in contrast with the shorter-term SYMPLICITY HTN-3 trial, in which no significant difference was seen between RDN and a sham procedure. The better trained operators in the centres participating in SYMPLICTY HTN-2 may in part explain this difference. 

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