Abstract: We found 12 eligible studies (1149 participants). In four studies, renal denervation was compared to sham procedure; one study compared a proximal ablation to a complete renal artery denervation; in the remaining, renal denervation was tested against standard or intensified antihypertensive therapy. None of the included trials was designed to look at hard clinical end points as primary outcomes. When compared to control, there was low quality evidence that renal denervation did not reduce the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (4 studies, 823 participants; RR 1.15, 95% CI 0.36 to 3.72), or unstable angina (2 studies, 201 participants; RR 0.63, 95% CI 0.08 to 5.06), and moderate quality evidence that it had no effect on 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (5 studies, 797 participants; MD 0.28 mmHg, 95% CI -3.74 to 4.29), diastolic BP (4 studies, 756 participants; MD 0.93 mmHg, 95% CI -4.50 to 6.36), office measured systolic BP (6 studies, 886 participants; MD -4.08 mmHg, 95% CI -15.26 to 7.11), or diastolic BP (5 studies, 845 participants; MD -1.30 mmHg, 95% CI -7.30 to 4.69). Furthermore, low quality evidence suggested that this procedure produced no effect on either serum creatinine (3 studies, 736 participants, MD 0.01 mg/dL; 95% CI -0.12 to 0.14), estimated glomerular filtration rate (eGFR), or creatinine clearance (4 studies, 837 participants; MD -2.09 mL/min, 95% CI -8.12 to 3.95). Based on low-quality evidence, renal denervation significantly increased bradycardia episodes compared to control (3 studies, 220 participants; RR 6.63, 95% CI 1.19 to 36.84), while the risk of other adverse events was comparable or not assessable. Data were sparse or absent for all cause mortality, hospitalisation, fatal cardiovascular events, quality of life, atrial fibrillation episodes, left ventricular hypertrophy, sleep apnoea severity, need for renal replacement therapy, and metabolic profile. The quality of the evidence was low for cardiovascular outcomes and adverse events and moderate for lack of effect on blood pressure and renal function. In patients with resistant hypertension, there is low quality evidence that renal denervation does not change major cardiovascular events, and renal function. There was moderate quality evidence that it does not change blood pressure and and low quality evidence that it caused an increaseof bradycardia episodes. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardized procedural methods are necessary to clarify the utility of this procedure in this population.

Plain-language summary: Twelve studies of variable quality were identified that included a total of 1149 participants. There was high heterogeneity among studies for design, methods, and blinding of investigators. Most of the studies assessed the impact of renal denervation on surrogate (e.g. blood pressure control), rather than patient-centred outcomes (e.g. mortality or quality of life). Overall, there was no evidence of benefits of renal denervation over standard treatment on cardiovascular morbidity and mortality. Similarly, renal denervation had no tangible effects on blood pressure control and renal function. However, it was associated with an increased risk of episodes of bradycardia (very slow heart rate). The quality of the evidence was low for cardiovascular morbidity and adverse events and moderate for lack of effect on blood pressure and renal function. The evidence is current to 17 February 2016. Current evidence is inconclusive to support the use of renal denervation to improve cardiovascular and renal risk and blood pressure control in patients with resistant hypertension. Future studies targeting patient-centred outcomes, with longer duration and larger number of participants are needed to identify whether individuals can benefit from this procedure.