Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Arterial Hypertension—clinical trials update 2023

Hypertension Research volume 46, pages 2159–2167 (2023)Cite this article

Abstract

Arterial hypertension is associated with increased morbidity and mortality and research in the field is highly dynamic. This summary reviews the most important clinical trials published in 2022 and early 2023. Findings on new pharmacological approaches to treat resistant hypertension are presented and new knowledge about the optimal timing of the antihypertensive medication intake is discussed. It is focused on optimal blood pressure treatment targets and the problem of treatment and guideline inertia is acknowledged. Information about pregnancy-related hypertension is presented and blood pressure control following percutaneous thrombectomy after ischemic stroke is discussed. Finally, novel clinical data on device-based approaches to treat hypertension are summarized.

The hypertension trials update summarizes the most important clincal trials on hypertension research in 2022 and early 2023. CTD – chlorthalidone, CV – cardiovascular, HCT – hydrochlorothiazide, SBP – systolic blood pressure, RDN – renal denervation *depicts systolic blood pressure only.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dicker D, Nguyen G, Abate D, Abate KH, Abay SM, Abbafati C, et al. Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1684–735. https://doi.org/10.1016/S0140-6736(18)31891-9

    Article  Google Scholar 

  2. Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marzcak L, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015. JAMA. 2017;317:165–82. https://doi.org/10.1001/jama.2016.19043

    Article  PubMed  Google Scholar 

  3. Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104. https://doi.org/10.1093/eurheartj/ehy339

    Article  PubMed  Google Scholar 

  4. Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR et al. Resistant hypertension: detection, evaluation, and management: A scientific statement from the American Heart Association. Hypertension. 2018;72. https://doi.org/10.1161/HYP.0000000000000084

  5. Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P. Prevalence of apparent treatment-resistant hypertension in the United States. Hypertension. 2019;73:424–31. https://doi.org/10.1161/HYPERTENSIONAHA.118.12191

    Article  CAS  PubMed  Google Scholar 

  6. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125:1635–42. https://doi.org/10.1161/CIRCULATIONAHA.111.068064

    Article  PubMed  PubMed Central  Google Scholar 

  7. Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ. 2012;345:e7473. https://doi.org/10.1136/bmj.e7473

    Article  PubMed  Google Scholar 

  8. Williams B. Resistant hypertension: an unmet treatment need. Lancet. 2009;374:1396–8. https://doi.org/10.1016/S0140-6736(09)61600-7

    Article  PubMed  Google Scholar 

  9. Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52:1749–57. https://doi.org/10.1016/j.jacc.2008.08.036

    Article  PubMed  Google Scholar 

  10. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol. 2018;71:e127–e248. https://doi.org/10.1016/j.jacc.2017.11.006

    Article  PubMed  Google Scholar 

  11. Götzinger F, Kunz M, Lauder L, Böhm M, Mahfoud F. Arterial hypertension - clinical trials update 2022. Hypertens Res. 2022;45:1140–6. https://doi.org/10.1038/s41440-022-00931-2

    Article  PubMed  Google Scholar 

  12. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–9. https://doi.org/10.1016/S0140-6736(10)62039-9

    Article  PubMed  Google Scholar 

  13. Bhatt DL, Vaduganathan M, Kandzari DE, Leon MB, Rocha-Singh K, Townsend RR, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet. 2022;400:1405–16. https://doi.org/10.1016/S0140-6736(22)01787-1

    Article  PubMed  Google Scholar 

  14. Esler MD, Böhm M, Sievert H, Rump CL, Schmieder RE, Krum H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J. 2014;35:1752–9. https://doi.org/10.1093/eurheartj/ehu209

    Article  PubMed  PubMed Central  Google Scholar 

  15. Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023;46:108–18. https://doi.org/10.1038/s41440-022-01070-4

    Article  CAS  PubMed  Google Scholar 

  16. Freeman MW, Halvorsen YD, Marshall W, Pater M, Isaacsohn J, Pearce C, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. New Eng J Med. 2023;388:395–405. https://doi.org/10.1056/NEJMoa2213169

    Article  CAS  PubMed  Google Scholar 

  17. Fagard RH, Thijs L, Staessen JA, Clement DL, de Buyzere ML, de Bacquer DA. Night–day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens. 2009;23:645–53. https://doi.org/10.1038/jhh.2009.9

    Article  CAS  PubMed  Google Scholar 

  18. Kario K. Morning surge in blood pressure and cardiovascular risk. Hypertension. 2010;56:765–73. https://doi.org/10.1161/HYPERTENSIONAHA.110.157149

    Article  CAS  PubMed  Google Scholar 

  19. Kario K, Hoshide S, Mizuno H, Kabutoya T, Nishizawa M, Yoshida T, et al. Nighttime hemodynamic phenotype. A novel risk factor for cardiovascular disease, especially heart failure: the practitioner-based nationwide JAMP study. Clin Res Cardiol. 2023;112:98–110. https://doi.org/10.1007/s00392-022-02051-w

    Article  PubMed  Google Scholar 

  20. Hermida RC, Calvo C, Ayala DE, Fernández JR, Covelo M, Mojón A, et al. Treatment of non-dipper hypertension with bedtime administration of valsartan. J Hypertens. 2005;23:1913–22. https://doi.org/10.1097/01.hjh.0000182522.21569.c5

    Article  CAS  PubMed  Google Scholar 

  21. Ho CLB, Chowdhury EK, Doust J, Nelson MR, Reid CM. The effect of taking blood pressure lowering medication at night on cardiovascular disease risk. A systematic review. J Hum Hypertens. 2021;35:308–14. https://doi.org/10.1038/s41371-020-00469-1

    Article  PubMed  Google Scholar 

  22. Mackenzie IS, Rogers A, Poulter NR, Williams B, Brown MJ, Webb DJ, et al. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. Lancet. 2022;400:1417–25. https://doi.org/10.1016/S0140-6736(22)01786-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. SPRINT Research Group, Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Enl J Med. 2015;373:2103–16. https://doi.org/10.1056/NEJMoa1511939

    Article  CAS  Google Scholar 

  24. Jaeger BC, Bress AP, Bundy JD, Cheung AK, Cushman WC, Drawz PE, et al. Longer-term all-cause and cardiovascular mortality with intensive blood pressure control. JAMA Cardiol. 2022;7:1138 https://doi.org/10.1001/jamacardio.2022.3345

    Article  PubMed  Google Scholar 

  25. Agarwal R. Hydrochlorothiazide versus chlorthalidone: What is the difference. Circulation. 2022;146:1641–3. https://doi.org/10.1161/CIRCULATIONAHA.122.061029

    Article  PubMed  Google Scholar 

  26. Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide. Hypertension. 2011;57:689–94. https://doi.org/10.1161/HYPERTENSIONAHA.110.161505

    Article  CAS  PubMed  Google Scholar 

  27. Ishani A, Cushman WC, Leatherman SM, Lew RA, Woods P, Glassman PA, et al. Chlorthalidone vs. Hydrochlorothiazide for hypertension–cardiovascular events. N Engl J Med. 2022;387:2401–10. https://doi.org/10.1056/NEJMoa2212270

    Article  CAS  PubMed  Google Scholar 

  28. Pathak A, Poulter NR, Kavanagh M, Kreutz R, Burnier M. Improving the management of hypertension by tackling awareness, adherence, and clinical inertia: a symposium report. Am J Cardiovasc Drugs. 2022;22:251–61. https://doi.org/10.1007/s40256-021-00505-6

    Article  PubMed  Google Scholar 

  29. Ali DH, Kiliç B, Hart HE, Bots ML, Biermans MCJ, Spiering W, et al. Therapeutic inertia in the management of hypertension in primary care. J Hypertens. 2021;39:1238–45. https://doi.org/10.1097/HJH.0000000000002783

    Article  CAS  PubMed  Google Scholar 

  30. Ferrari P, Hess L, Pechere-Bertschi A, Muggli F, Burnier M. Reasons for not intensifying antihypertensive treatment (RIAT). J Hypertens. 2004;22:1221–9. https://doi.org/10.1097/00004872-200406000-00024

    Article  CAS  PubMed  Google Scholar 

  31. Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension. Hypertension.2021;77:692–705. https://doi.org/10.1161/HYPERTENSIONAHA.120.15781.

    Article  CAS  PubMed  Google Scholar 

  32. Mahfoud F, Kieble M, Enners S, Kintscher U, Laufs U, Böhm M, et al. Use of fixed-dose combination antihypertensives in Germany between 2016 and 2020: an example of guideline inertia. Clin Res Cardiol. 2023;112:197–202. https://doi.org/10.1007/s00392-022-01993-5

    Article  PubMed  Google Scholar 

  33. Schmieder RE, Wassmann S, Predel HG, Weisser B, Blettenberg J, Gillessen A, et al. Improved persistence to medication, decreased cardiovascular events and reduced all-cause mortality in hypertensive patients with use of single-pill combinations: results from the START-study. Hypertension. 2023;80:1127–35. https://doi.org/10.1161/HYPERTENSIONAHA.122.20810

    Article  CAS  PubMed  Google Scholar 

  34. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2:e323–e333. https://doi.org/10.1016/S2214-109X(14)70227-X

    Article  PubMed  Google Scholar 

  35. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Obstet Gynecol. 2013;122:1122-31. https://doi.org/10.1097/01.AOG.0000437382.03963.88

  36. Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, et al. Treatment for mild chronic hypertension during pregnancy. N Eng J Med. 2022;386:1781–92. https://doi.org/10.1056/NEJMoa2201295

    Article  CAS  Google Scholar 

  37. Feigin VL, Stark BA, Johnson CO, Roth GA, Bisignano C, Abady GG, et al. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20:795–820. https://doi.org/10.1016/S1474-4422(21)00252-0

    Article  CAS  Google Scholar 

  38. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49. https://doi.org/10.1161/STR.0000000000000158

  39. Feske SK. Ischemic stroke. Am J Med. 2021;134:1457–64. https://doi.org/10.1016/j.amjmed.2021.07.027

    Article  PubMed  Google Scholar 

  40. Yang P, Song L, Zhang Y, Zhang X, Chen X, Li Y, et al. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial. Lancet. 2022;400:1585–96. https://doi.org/10.1016/S0140-6736(22)01882-7

    Article  PubMed  Google Scholar 

  41. Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009;361:932–4. https://doi.org/10.1056/NEJMc0904179

    Article  CAS  PubMed  Google Scholar 

  42. Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J. 2012;33:1058–66. https://doi.org/10.1093/eurheartj/ehs041

    Article  CAS  PubMed  Google Scholar 

  43. Mahfoud F, Kandzari DE, Kario K, Townsend RR, Weber MA, Schmieder RE, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. 2022;399:1401–10. https://doi.org/10.1016/S0140-6736(22)00455-X

    Article  CAS  PubMed  Google Scholar 

  44. Kandzari DE, Böhm 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. https://doi.org/10.1016/S0140-6736(18)30951-6

    Article  PubMed  Google Scholar 

  45. Kario K, Mahfoud F, Kandzari DE, Townsend RR, Weber MA, Schmieder RE, et al. Long-term reduction in morning and nighttime blood pressure after renal denervation: 36-month results from SPYRAL HTN-ON MED trial. Hypertens Res. 2023;46:280–8. https://doi.org/10.1038/s41440-022-01042-8

    Article  CAS  PubMed  Google Scholar 

  46. Azizi M, Saxena M, Wang Y, Jenkins JS, Devireddy C, Rader F, et al. Endovascular ultrasound renal denervation to treat hypertension. JAMA. 2023;329:651 https://doi.org/10.1001/jama.2023.0713

    Article  PubMed  Google Scholar 

  47. Mahfoud F, Mancia G, Schmieder RE, Ruilope L, Narkiewicz K, Schlaich M, et al. Cardiovascular risk reduction after renal denervation according to time in therapeutic systolic blood pressure range. J Am Coll Cardiol. 2022;80:1871–80. https://doi.org/10.1016/j.jacc.2022.08.802

    Article  CAS  PubMed  Google Scholar 

  48. 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. https://doi.org/10.1016/S0140-6736(20)30554-7

    Article  PubMed  Google Scholar 

  49. 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. https://doi.org/10.1016/S0140-6736(21)00788-1

    Article  CAS  PubMed  Google Scholar 

  50. 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. https://doi.org/10.1016/S0140-6736(18)31082-1

    Article  PubMed  Google Scholar 

  51. Barbato E, Azizi M, Schmieder RE, Lauder L, Böhm M, Brouwers S et al. Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. Published online February 15, 2023. https://doi.org/10.1093/eurheartj/ehad054

Download references

Author information

Authors and Affiliations

  1. From the Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital Saarland, 66424, Homburg, Germany

    Felix Götzinger, Michael Kunz, Lucas Lauder, Michael Böhm & Felix Mahfoud

Authors
  1. Felix Götzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Kunz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucas Lauder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Böhm
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Felix Mahfoud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Felix Götzinger.

Ethics declarations

Conflict of interest

FG received speaker honoraria from AstraZeneca and is supported by the German Heart Foundation/German Foundation of Heart Research. LL received speaker honoraria from Medtronic and ReCor Medical. MB is supported by Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Deutsche Forschungsgemeinschaft (DFG) (TRR 219 Project-ID 322900939, S-01, M-02 and M-06), Medtronic, Novartis, ReCor Medical, Servier, and Vifor. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), DFG (SFB TRR 219 Project-ID 322900939) and by the German Heart Foundation/German Foundation of Heart Research and has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, and ReCor Medical. MK has nothing to declare.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Götzinger, F., Kunz, M., Lauder, L. et al. Arterial Hypertension—clinical trials update 2023. Hypertens Res 46, 2159–2167 (2023). https://doi.org/10.1038/s41440-023-01359-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01359-y

Keywords

This article is cited by

Search

Advanced search

Quick links