Renal nerve denervation for resistant hypertension : systematic review and meta-analysis

Abstract

Systemic hypertension is a major burden to the individual and society. Its association with major adverse cardiac and cerebral events and beneficial effects of antihypertensive therapy are undisputed. However, despite multidrug therapy, blood pressures are frequently sub-optimally controlled. Controversy regarding the effects of Renal Nerve Denervation (RND) for Resistant Hypertension (RH) has surfaced after a randomized, single-blind, multicenter, prospective, controlled clinical trial Simplicity HTN-3 in 2014 did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal artery denervation as compared with a sham control. Many other previous clinical data show that RND reduces blood pressure in patients with resistant hypertension however in results from Symplicity HTN-3 suggested that the effectiveness of RND is still controversial. Objective To evaluate the short-and long-term effects of renal nerve denervation in individuals with resistant hypertension on: • Patient-centered endpoints including blood pressure control; Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) • 24 hours Ambulatory Blood Pressure Monitoring (AMBP) Search method We searched research published since January 1, 2009 through computer (since the first report of RND in 2009) to the clinical studies published until 15 December 2015 in PubMed, Cochrane and Library in Clinicaltrial.gov database. The following keywords were employed: "hypertension" or "blood pressure" or "resistant hypertension" or "refractory hypertension" or "uncontrolled hypertension" or "susceptible drug-resistant hypertension" or "and" denervation "or" catheter-based renal denervation "or" renal sympathetic denervation "or" percutaneous renalsympathectomy "or" radiofrequency catheter-based renal sympathetic denervation "or renal nerve denervation. Selection Criteria Literature screening mainly according to the inclusion criteria and exclusion criteria, through literature reading of articles and abstract screening; to meet the inclusion criteria and exclusion standard. Clinical study full text study were done to extract relevant data; if reading the text found exactly the same research group, only selected the related literature. Data Collection and analysis Data were collected by one author (AKM) and checked by other author (AS). Potential eligible studies were excluded when the results presentation prevented adequate extraction of data. Main Results In this systematic review and meta-analysis, according to inclusion criteria and exclusion criteria, 38 clinical studies on RND were included. Total of 38 studies, 6 studies were Randomized Control Trials, 10 studies were prospective observational study with control group and remaining 22 studies were prospective observational studies without control group. Out of all 38 studies included 33 studies involving 2135 cases of patients reported the result of SBP at 6 months after RND, 27 studies involving 1377 patients reported the result of DBP 6 months after RND. The statistical result shows that RND can reduce 22.50 mmHg of SBP [95% confidence interval (CI: -24.14, -20.86), P<0.00001, Z=26.90] and 8.99 mmHg of DBP [95% Confidence interval (CI: -10.51, -7.46), P<0.00001, Z = 11.56].For 24 hoursambulatory blood pressure monitoring over all clinical research, RND can reduce the systolic blood pressure of 10.44 mmHg[95% confidence interval (CI: -12.85, -8.02), P=0.0002, Z=8.46]; RND can also reduce the diastolic blood pressure of 5.88 mmHg[95% confidence interval (CI: -6.71, -5.05), P < 0.00001, Z=13.88]. Authors Conclusions: The meta-analysis observed that RND could effectively reduce the systolic blood pressure in office and 24-hour ambulatory blood pressure monitoring in patients with resistant hypertension. These results suggest that the RND for patients with resistant hypertension can play a hypotensive effect; RND could exert protective effect on patients with resistant high blood pressure through its antihypertensive effect.