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Efficacy and Safety of Azelnidipine as an Antihypertensive Compared to Amlodipine: A Systematic Review and Meta-analysis

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Abstract

Introduction

Azelnidipine is one of the newer Calcium Channel Blockers (CCB) approved in China, Japan, and India. Some studies have found that the blood pressure-lowering effect of azelnidipine is more than amlodipine, and others found the effect similar.

Aim

This meta-analysis was conducted to evaluate the efficacy of azelnidipine in managing hypertensive patients by lowering Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) as compared to amlodipine.

Methods

PubMed/MEDLINE, Google Scholar, PROQUEST, and International Clinical Trial Registry Platform (ICTRP) were searched for published articles to evaluate the clinical efficacy of azelnidipine in the management of hypertension patients. Data were extracted from the selected 11 randomized clinical trials (RCTs). The risk of bias 2 (RoB2) tool was used for the quality assessment of the included studies, and the random-effects model was used to estimate the effect size.

Results

There were no statistically significant differences in the reduction of SBP (Mean Difference, MD: − 1.07; 95% CI: − 4.10, 1.95, p-value: 0.49) and DBP (MD: 0.27; 95% CI: − 2.66, 3.20, p-value: 0.86) between both the drugs. In terms of HR reduction, there was a statistically significant difference (MD: − 3.63; 95% CI: − 5.27, − 2.00, p-value: < 0.0001) between both drugs. Egger’s test excluded any publication bias for the included studies (p = 0.21). Meta-regression excluded the effect of the duration of treatment on outcome parameters.

Conclusion

Though no significant difference between azelnidipine and amlodipine was found, in terms of reduction in SBP and DBP, azelnidipine reduced heart rate significantly compared to amlodipine.

PROSPERO Registration

CRD42023390361.

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Change history

  • 08 October 2023

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References

  1. Fuchs FD, Whelton PK. High blood pressure and cardiovascular disease. Hypertension. 2020;75:285–92.

    Article  CAS  PubMed  Google Scholar 

  2. Hypertension [Internet]. World Heart Federation. https://world-heart-federation.org/what-we-do/hypertension/ [cited 2023 Jan 7].

  3. Tocci G, Battistoni A, Passerini J, Musumeci MB, Francia P, Ferrucci A, Volpe M. Calcium channel blockers and hypertension. J Cardiovasc Pharmacol Ther. 2015;20:121–30.

    Article  CAS  PubMed  Google Scholar 

  4. Vukadinović D, Scholz SS, Messerli FH, Weber MA, Williams B, Böhm M, Mahfoud F. Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials. J Hypertens. 2019;37:2093–103.

    Article  PubMed  Google Scholar 

  5. Chen BL, Zhang YZ, Luo JQ, Zhang W. Clinical use of azelnidipine in the treatment of hypertension in Chinese patients. Ther Clin Risk Manag. 2015;11:309–18.

    PubMed  PubMed Central  Google Scholar 

  6. Wellington K, Scott LJ. Azelnidipine. Drugs. 2003;63:2613–21.

    Article  CAS  PubMed  Google Scholar 

  7. CDSCO. Recommendations of the SEC [Internet]; 2020. https://www.cdsco.gov.in/opencms/resources/UploadCDSCOWeb/2018/UploadCommitteeFiles/73rdSECCardiovascular%20&%20Renal6fe20.pdf [cited 2022 Dec 24].

  8. Shokoji T, Fujisawa Y, Kiyomoto H, Rahman M, Sun GP, Fan YY, Kimura S, Kohno M, Abe Y, Nishiyama A. Effects of a new calcium channel blocker, azelnidipine, on systemic hemodynamics and renal sympathetic nerve activity in spontaneously hypertensive rats. Hypertens Res. 2005;28:1017–23.

    Article  CAS  PubMed  Google Scholar 

  9. Nakamoto M, Ohya Y, Sakima A, Yamazato M, Takishita S. Azelnidipine attenuates cardiovascular and sympathetic responses to air-jet stress in genetically hypertensive rats. Hypertens Res. 2007;30:359–66.

    Article  CAS  PubMed  Google Scholar 

  10. Nakamura T, Sugaya T, Kawagoe Y, Suzuki T, Ueda Y, Koide H, Inoue T, Node K. Azelnidipine reduces urinary protein excretion and urinary liver-type fatty acid binding protein in patients with hypertensive chronic kidney disease. Am J Med Sci. 2007;333:321–6.

    Article  PubMed  Google Scholar 

  11. Takenaka T, Seto T, Okayama M, Kojima E, Nodaira Y, Sueyoshi K, Kikuta T, Watanabe Y, Inoue T, Takane H, Ohno Y, Suzuki H. Long-term effects of calcium antagonists on augmentation index in hypertensive patients with chronic kidney disease: a randomized controlled study. Am J Nephrol. 2012;35:416–23.

    Article  CAS  PubMed  Google Scholar 

  12. Zhao X, Wu F, Jia S, Qu P, Li H, Zhao X, Cao B, Lin Y, Wang M. Azelnidipine and amlodipine: a comparison of their effects and safety in a randomized double-blinded clinical trial in Chinese essential hypertensive patients. Clin Exp Hypertens. 2010;32:372–6.

    Article  CAS  PubMed  Google Scholar 

  13. Yamagishi T. Efficacy of azelnidipine on home blood pressure and pulse rate in patients with essential hypertension: comparison with amlodipine. Hypertens Res. 2006;29:767–73.

    Article  CAS  PubMed  Google Scholar 

  14. Tawaramoto K, Kaneto H, Hashiramoto M, Kawasaki F, Tatsumi F, Shimoda M, Kamei S, Matsuki M, Mune T, Kaku K. Azelnidipine, but not amlodipine, reduces urinary albumin excretion and carotid atherosclerosis in subjects with type 2 diabetes: blood pressure control with olmesartan and azelnidipine in Type 2 diabetes (BOAT2 study). Diabetol Metab Syndr. 2015;7:80.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Motoki H, Koyama J, Izawa A, Tomita T, Miyashita Y, Takahashi M, Ikeda U. Impact of azelnidipine and amlodipine on left ventricular mass and longitudinal function in hypertensive patients with left ventricular hypertrophy. Echocardiography. 2014;31:1230–8.

    Article  PubMed  Google Scholar 

  16. Kuramoto K, Ichikawa S, Hirai A, Kanada S, Nakachi T, Ogihara T. Azelnidipine and amlodipine: a comparison of their pharmacokinetics and effects on ambulatory blood pressure. Hypertens Res. 2003;26:201–8.

    Article  CAS  PubMed  Google Scholar 

  17. Kojima T, Miyauchi K, Yokoyama T, Yokoyama K, Kurata T, Suwa S, Kawamura M, Tamura H, Okazaki S, Inoue K, Fujiwara Y, Sumiyoshi M, Tanimoto K, Nakazato Y, Yamagami S, Hiro T, Komiyama N, Daida H. Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo University (ALPS-J). Circ J. 2011;75:1071–9.

    Article  CAS  PubMed  Google Scholar 

  18. Inomata J, Murai H, Kaneko S, Hamaoka T, Ikeda T, Kobayashi D, Usui S, Furusho H, Sugiyama Y, Takata S, Takamura M. Differential effects of azelnidipine and amlodipine on sympathetic nerve activity in patients with primary hypertension. J Hypertens. 2014;32:1898–904.

    Article  CAS  PubMed  Google Scholar 

  19. Fukao K, Shimada K, Hiki M, Kiyanagi T, Hirose K, Kume A, Ohsaka H, Matsumori R, Kurata T, Miyazaki T, Daida H. Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between azelnidipine and amlodipine on glucose tolerance and endothelial function—a crossover trial (AGENT). Cardiovasc Diabetol. 2011;10:1–12.

    Article  Google Scholar 

  20. Eguchi K, Tomizawa H, Ishikawa J, Hoshide S, Fukuda T, Numao T, Shimada K, Kario K. Effects of new calcium channel blocker, azelnidipine, and amlodipine on baroreflex sensitivity and ambulatory blood pressure. J Cardiovasc Pharmacol. 2007;49:394–400.

    Article  CAS  PubMed  Google Scholar 

  21. An updated guideline for reporting systematic reviews [Internet]. Equator Network; 2020. https://www.equator-network.org [cited 2022 Dec 24].

  22. PROSPERO [Internet]. University of York. https://www.crd.york.ac.uk/prospero/ [cited 2023 Jan 17].

  23. Cochrane Handbook for Systematic Reviews of Interventions | Cochrane Training [Internet]. https://training.cochrane.org/handbook [cited 2022 Dec 24].

  24. RoB 2: A revised Cochrane risk-of-bias tool for randomized trials | Cochrane Bias [Internet]. https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials [cited 2022 Dec 24].

  25. Cochrane Handbook for Systematic Reviews of Interventions | Cochrane Training [Internet]. https://training.cochrane.org/handbook#how-to-cite [cited 2023 Aug 20].

  26. Xiao Y, Hu G. The effects of azelnidipine and amlodipine in treatment of mild to moderate hypertension: a systematic review. Int J Clin Exp Med. 2017;10:11273–81.

    Google Scholar 

  27. Shinomiya K, Mizushige K, Fukunaga M, Masugata H, Ohmori K, Kohno M, Senda S. Antioxidant effect of a new calcium antagonist, azelnidipine, in cultured human arterial endothelial cells. J Int Med Res. 2004;32:170–5.

    Article  CAS  PubMed  Google Scholar 

  28. Sofy AA, Abdelsattar AT, Mohammed OM, Shareef MA, Alamodi AA, Nso N, Payton M, Masoud AT. Amlodipine compared with benidipine in the management of hypertension: a systematic review and meta-analysis. High Blood Press Cardiovasc Prev. 2020;27(6):527–37.

    Article  CAS  PubMed  Google Scholar 

  29. Ram CVS. Therapeutic usefulness of a novel calcium channel blocker azelnidipine in the treatment of hypertension: a narrative review. Cardiol Ther. 2022;11:473–89.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Community Medicine and Family Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India

    Debkumar Pal

  2. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India

    Shampa Maji & Rituparna Maiti

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  1. Debkumar Pal
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Corresponding author

Correspondence to Shampa Maji.

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Conflict of interest

None to declare.

Ethical approval

We took approval from the Institutional Ethics Committee before conducting this study. Reference Number: T/IM-NF/Pharm/22/141.

Funding

None to declare.

Availability of data

All data of this work are available through contacting the corresponding author.

Author contributions

Debkumar Pal: Concept and design, Literature Search, Study selection and data collection, Data extraction and management, and drafting of the manuscript, Final approval of the manuscript. Shampa Maji: Literature Search, Study selection and data collection, Data Analysis and interpretation of data, Critical revision of the manuscript for important intellectual content, Final approval of the manuscript. Rituparna Maiti: Study selection and data collection, data extraction and management, Data Analysis and interpretation of data, Critical revision of the manuscript for important intellectual content, Final approval of the manuscript.

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Pal, D., Maji, S. & Maiti, R. Efficacy and Safety of Azelnidipine as an Antihypertensive Compared to Amlodipine: A Systematic Review and Meta-analysis. High Blood Press Cardiovasc Prev 30, 401–410 (2023). https://doi.org/10.1007/s40292-023-00601-5

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