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Effects of renal denervation on blood pressures in patients with hypertension: a systematic review and meta-analysis of randomized sham-controlled trials

A Comment to this article was published on 24 December 2021

A Comment to this article was published on 16 December 2021

An Editorial to this article was published on 10 December 2021

An Editorial to this article was published on 15 October 2021

Abstract

The efficacy of renal denervation has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after renal denervation in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of renal denervation on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 25 May 2021 to identify randomized, sham-controlled trials of renal denervation. The primary endpoint was change in 24 h ambulatory systolic blood pressure with renal denervation versus sham control. The secondary endpoints were daytime and nighttime systolic blood pressure, and office systolic blood pressure. A sub-analysis determined outcomes by medication, procedure, and device. From nine trials, 1555 patients with hypertension were randomized to undergo renal denervation (n = 885) or a sham procedure (n = 670). At 2–6 months after treatment, renal denervation significantly reduced 24 h ambulatory systolic blood pressure by 3.31 mmHg (95% confidence interval: −4.69, −1.94) compared with the sham procedure (p < 0.001). Renal denervation also reduced daytime SBP by 3.53 mmHg (−5.28, −1.78; p < 0.001), nighttime SBP by 3.20 mmHg (−5.46, −0.94; p = 0.006), and office SBP by 5.25 mmHg (−7.09, −3.40; p < 0.001) versus the sham control group. There were no significant differences in the magnitude of blood pressure reduction between first- and second-generation trials, between devices, or with or without medication. These data from randomized sham-controlled trials showed that renal denervation significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension. Future trials should investigate the long-term efficacy and safety of renal denervation.

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References

  1. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.

    PubMed  Google Scholar 

  2. Collaboration NCDRF. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet. 2017;389:37–55.

    Google Scholar 

  3. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

    PubMed  Google Scholar 

  4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.

    PubMed  Google Scholar 

  5. Katsurada K, Ogoyama Y, Imai Y, Patel KP, Kario K. New Horizons in the Treatment of Hypertension: renal denervation based on experimental rationale. Hypertens Res. 2021. https://doi.org/10.1038/s41440-021-00746-7. [Epub ahead of print].

  6. Nishi EE, Lopes NR, Gomes GN, Perry JC, Sato AYS, Naffah-Mazzacoratti MG, et al. Renal denervation reduces sympathetic overactivation, brain oxidative stress, and renal injury in rats with renovascular hypertension independent of its effects on reducing blood pressure. Hypertens Res. 2019;42:628–40.

    PubMed  Google Scholar 

  7. Morisawa N, Kitada K, Fujisawa Y, Nakano D, Yamazaki D, Kobuchi S, et al. Renal sympathetic nerve activity regulates cardiovascular energy expenditure in rats fed high salt. Hypertens Res. 2020;43:482–91.

    CAS  PubMed  Google Scholar 

  8. Page IH, Heuer GJ. The Effect of Renal Denervation on the Level of Arterial Blood Pressure and Renal Function in Essential Hypertension. J Clin Investig. 1935;14:27–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953;152:1501–4.

    CAS  PubMed  Google Scholar 

  10. Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroIntervention. 2012;8:57–61.

    PubMed  Google Scholar 

  11. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.

    PubMed  Google Scholar 

  12. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–9.

    PubMed  Google Scholar 

  13. Sievert H, Schofer J, Ormiston J, Hoppe UC, Meredith IT, Walters DL, et al. Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study. EuroIntervention. 2015;10:1213–20.

    PubMed  Google Scholar 

  14. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401.

    CAS  PubMed  Google Scholar 

  15. Schmieder RE, Mahfoud F, Mancia G, Azizi M, Bohm M, Dimitriadis K, et al. European Society of Hypertension position paper on renal denervation. 2021. J Hypertens. 2021;39:1733–41.

    CAS  PubMed  Google Scholar 

  16. Azizi M, Sanghvi K, Saxena M, Gosse P, Reilly JP, Levy T, et al. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet. 2021;397:2476–86.

    CAS  PubMed  Google Scholar 

  17. Kario K, Yokoi Y, Okamura K, Fujihara M, Ogoyama Y, Yamamoto E, et al. Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial. Hypertens Res. 2021. https://doi.org/10.1038/s41440-021-00754-7. [Epub ahead of print].

  18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906.

    PubMed  Google Scholar 

  19. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Google Scholar 

  20. Weber MA, Kirtane AJ, Weir MR, Radhakrishnan J, Das T, Berk M, et al. The REDUCE HTN: REINFORCE: Randomized, Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension. JACC Cardiovasc Interv. 2020;13:461–70.

    PubMed  Google Scholar 

  21. Desch S, Okon T, Heinemann D, Kulle K, Rohnert K, Sonnabend M, et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension. 2015;65:1202–8.

    CAS  PubMed  Google Scholar 

  22. Mathiassen ON, Vase H, Bech JN, Christensen KL, Buus NH, Schroeder AP, et al. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial. J Hypertens. 2016;34:1639–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018;391:2346–55.

    PubMed  Google Scholar 

  24. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018;391:2335–45.

    PubMed  Google Scholar 

  25. Böhm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020;395:1444–51.

    PubMed  Google Scholar 

  26. Krum H, Schlaich MP, Sobotka PA, Böhm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014;383:622–9.

    PubMed  Google Scholar 

  27. Mahfoud F, Bohm M, Schmieder R, Narkiewicz K, Ewen S, Ruilope L, et al. Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry. Eur Heart J. 2019;40:3474–82.

    PubMed  PubMed Central  Google Scholar 

  28. Denegri A, Naduvathumuriyil T, Luscher TF, Sudano I. Renal nerve ablation reduces blood pressure in resistant hypertension: Long-term clinical outcomes in a single-center experience. J Clin Hypertens (Greenwich). 2018;20:627–33.

    CAS  PubMed Central  Google Scholar 

  29. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387:957–67.

    PubMed  Google Scholar 

  30. Blood Pressure Lowering Treatment Trialists C. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397:1625–36.

    Google Scholar 

  31. Sakima A, Satonaka H, Nishida N, Yatsu K, Arima H. Optimal blood pressure targets for patients with hypertension: a systematic review and meta-analysis. Hypertens Res. 2019;42:483–95.

    PubMed  Google Scholar 

  32. Takami Y, Yamamoto K, Arima H, Sakima A. Target blood pressure level for the treatment of elderly hypertensive patients: a systematic review and meta-analysis of randomized trials. Hypertens Res. 2019;42:660–8.

    PubMed  Google Scholar 

  33. Mahfoud F, Schmieder RE, Azizi M, Pathak A, Sievert H, Tsioufis C, et al. Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future. Eur Heart J. 2017;38:3272–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang WY, Melgarejo JD, Thijs L, Zhang ZY, Boggia J, Wei FF, et al. Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes. JAMA. 2019;322:409–20.

    PubMed  PubMed Central  Google Scholar 

  35. Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, et al. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003;348:2407–15.

    PubMed  Google Scholar 

  36. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.

    CAS  PubMed  Google Scholar 

  37. Sega R, Facchetti R, Bombelli M, Cesana G, Corrao G, Grassi G, et al. Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation. 2005;111:1777–83.

    PubMed  Google Scholar 

  38. Soranna D, Zambon A, Corrao G, Zanchetti A, Parati G, Mancia G. Different effects of antihypertensive treatment on office and ambulatory blood pressure: a meta-analysis. J Hypertens. 2019;37:467–75.

    CAS  PubMed  Google Scholar 

  39. Kario K, Weber MA, Mahfoud F, Kandzari DE, Schmieder RE, Kirtane AJ, et al. Changes in 24-Hour Patterns of Blood Pressure in Hypertension Following Renal Denervation Therapy. Hypertension. 2019;74:244–49.

    CAS  Google Scholar 

  40. Kario K, Bohm M, Mahfoud F, Townsend RR, Weber MA, Patel M, et al. Twenty-Four-Hour Ambulatory Blood Pressure Reduction Patterns After Renal Denervation in the SPYRAL HTN-OFF MED Trial. Circulation. 2018;138:1602–4.

    PubMed  Google Scholar 

  41. Sardar P, Bhatt DL, Kirtane AJ, Kennedy KF, Chatterjee S, Giri J, et al. Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension. J Am Coll Cardiol. 2019;73:1633–42.

    PubMed  Google Scholar 

  42. Stavropoulos K, Patoulias D, Imprialos K, Doumas M, Katsimardou A, Dimitriadis K, et al. Efficacy and safety of renal denervation for the management of arterial hypertension: a systematic review and meta-analysis of randomized, sham-controlled, catheter-based trials. J Clin Hypertens (Greenwich). 2020;22:572–84.

    PubMed Central  Google Scholar 

  43. Dahal K, Khan M, Siddiqui N, Mina G, Katikaneni P, Modi K, et al. Renal Denervation in the Management of Hypertension: a Meta-Analysis of Sham-Controlled Trials. Cardiovasc Revasc Med. 2020;21:532–7.

    PubMed  Google Scholar 

  44. Kario K, Hoshide S, Mizuno H, Kabutoya T, Nishizawa M, Yoshida T, et al. Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis: Practitioner-Based Nationwide JAMP Study. Circulation. 2020;142:1810–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Fujiwara T, Hoshide S, Kanegae H, Kario K. Cardiovascular Event Risks Associated With Masked Nocturnal Hypertension Defined by Home Blood Pressure Monitoring in the J-HOP Nocturnal Blood Pressure Study. Hypertension. 2020;76:259–66.

    CAS  PubMed  Google Scholar 

  46. Hoshide S, Kanegae H, Kario K. Nighttime home blood pressure as a mediator of N-terminal pro-brain natriuretic peptide in cardiovascular events. Hypertens Res. 2021 (e-pub ahead of print 2021/07/11; https://doi.org/10.1038/s41440-021-00667-5.

  47. Kario K, Williams B. Nocturnal hypertension and heart failure: mechanisms, evidence, and new treatments. Hypertension. 2021;78:564–77.

    CAS  PubMed  Google Scholar 

  48. Kario K, Weber MA, Böhm M, Townsend RR, Mahfoud F, Schmieder RE, et al. Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial. Clin Res Cardiol. 2021;110:725–31.

    PubMed  Google Scholar 

  49. Persu A, Gordin D, Jacobs L, Thijs L, Bots ML, Spiering W, et al. Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis. J Hypertens. 2018;36:221–9.

    CAS  PubMed  Google Scholar 

  50. Azizi M, Daemen J, Lobo MD, Mahfoud F, Sharp ASP, Schmieder RE, et al. 12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation. JACC Cardiovasc Interv. 2020;13:2922–33.

    PubMed  Google Scholar 

  51. Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31:766–74.

    CAS  PubMed  Google Scholar 

  52. Kim S, Shin DW, Yun JM, Hwang Y, Park SK, Ko YJ, et al. Medication Adherence and the Risk of Cardiovascular Mortality and Hospitalization Among Patients With Newly Prescribed Antihypertensive Medications. Hypertension. 2016;67:506–12.

    CAS  PubMed  Google Scholar 

  53. Kario K, Yamamoto E, Tomita H, Okura T, Saito S, Ueno T, et al. Sufficient and Persistent Blood Pressure Reduction in the Final Long-Term Results From SYMPLICITY HTN-Japan- Safety and Efficacy of Renal Denervation at 3 Years. Circ J. 2019;83:622–9.

    CAS  PubMed  Google Scholar 

  54. Kim BK, Kim HS, Park SJ, Park CG, Seung KB, Gwon HC, et al. Long-term outcomes after renal denervation in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea). Hypertens Res. 2021;44:1099–104.

    CAS  PubMed  Google Scholar 

  55. Mahfoud F, Tunev S, Ewen S, Cremers B, Ruwart J, Schulz-Jander D, et al. Impact of Lesion Placement on Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation. J Am Coll Cardiol. 2015;66:1766–75.

    PubMed  Google Scholar 

  56. Pekarskiy SE, Baev AE, Mordovin VF, Semke GV, Ripp TM, Falkovskaya AU, et al. Denervation of the distal renal arterial branches vs. conventional main renal artery treatment: a randomized controlled trial for treatment of resistant hypertension. J Hypertens. 2017;35:369–75.

    CAS  PubMed  Google Scholar 

  57. Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man. J Am Coll Cardiol. 2014;64:635–43.

    PubMed  Google Scholar 

  58. Fengler K, Rommel KP, Blazek S, Besler C, Hartung P, von Roeder M, et al. A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN). Circulation. 2019;139:590–600.

    PubMed  Google Scholar 

  59. Townsend RR, Walton A, Hettrick DA, Hickey GL, Weil J, Sharp ASP, et al. Incidence of renal artery damage following percutaneous renal denervation with radio frequency renal artery ablation systems: Review and Meta-Analysis of published reports. EuroIntervention. 2020. https://doi.org/10.4244/EIJ-D-19-00902.

    Article  PubMed  Google Scholar 

  60. Sanders MF, Reitsma JB, Morpey M, Gremmels H, Bots ML, Pisano A, et al. Renal safety of catheter-based renal denervation: systematic review and meta-analysis. Nephrol Dial Transpl. 2017;32:1440–7.

    CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Dr Sawako Abe and Eriko Handa in Fukuoka University Medical Library. English language editing assistance was provided by Nicola Ryan, independent medical writer, funded by Jiichi Medical University.

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All authors contributed to the protocol. KT and MA conducted searches, screening and extraction, analyzed the data, YO and KT drafted the paper. KK helped conceive the study, provided valuable clinical expertize. HA designed the meta-analytic code, assisted with screening and extraction as well as providing valuable methodological expertize. SN, HS, HK, and MM provided valuable content expertize and assistance throughout the project. All authors provided valuable input when analyzing and interpreting the results, approved the final paper and provided valuable input in content.

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Correspondence to Hisatomi Arima or Kazuomi Kario.

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KK received speaker fees or works as a consultant to JIMRO Co., Ltd., and Terumo Co; research grant from Otsuka Medical Device Co., Ltd. outside the submitted work. Shinsuke Nanto MD PhD received speaker fees to JIMRO Co., Ltd., and Otsuka Medical Device Co.

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Ogoyama, Y., Tada, K., Abe, M. et al. Effects of renal denervation on blood pressures in patients with hypertension: a systematic review and meta-analysis of randomized sham-controlled trials. Hypertens Res 45, 210–220 (2022). https://doi.org/10.1038/s41440-021-00761-8

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