Effect of carvedilol rapid up-titration on malondialdehyde levels in patient with heart failure reduced ejection fraction

Abiseka Panji Baskoro; Habibie Arifianto; Trisulo Wasyanto; Heru Sulastomo; Ahmad Yasa; Niniek Purwaningtyas

doi:10.15562/bmj.v11i3.3765

Effect of carvedilol rapid up-titration on malondialdehyde levels in patient with heart failure reduced ejection fraction

Abiseka Panji Baskoro ,

Habibie Arifianto ,

Trisulo Wasyanto ,

Heru Sulastomo ,

Ahmad Yasa ,

Niniek Purwaningtyas ,

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DOI: https://doi.org/10.15562/bmj.v11i3.3765 |
Published: 2022-12-30

Abstract

Background: Malondialdehyde (MDA) is a marker that can assess the level of oxidative stress. Studies support that this marker can reflect the severity of heart failure. Carvedilol is a third-generation beta-blocker with antioxidant effects. Slow titration may contribute to the suboptimal dose use and therapeutic effect due to improved left ventricular systolic function and reduced dose-dependent mortality.

Aim: To determine the effect of rapid titration of carvedilol compared with standard titration according to standard guidelines on MDA levels in HFrEF (heart failure reduced ejection fraction) patients.

Methods: This study is a single-centre experimental study with a randomized, double-blind control trial conducted from October to December 2021. A total of 26 HFrEF patients undergoing treatment at UNS Hospital Sukoharjo were sequentially included in the study and then randomly divided into the rapid titration group carvedilol given an initial dose of 2 x 3.125 mg and increased every day with a target dose of 2 x 25 mg (or the maximum tolerated dose). The control group was given carvedilol dose titration according to standard guidelines. Blood plasma was taken on the first day before treatment and on the day the patient was discharged. MDA levels were checked by the ELISA method.

Results: The decrease in mean MDA levels was greater in the carvedilol rapid titration group than in the control group (2.84 ± 1.00 vs. 3.59 ± 2.55). However, these results were not statistically significant (p = 0.590). In the rapid titration group, carvedilol also showed a change in post-pre-MDA with a larger mean decrease (-0.55 ± 1.01) although not statistically significant (p = 0.157).

Conclusion: Rapid up-titration of carvedilol in patients with HFrEF during hospitalization can reduce MDA levels better than titration according to standard guidelines but is not statistically significant.

References

Pol AV, Gilst WH, Voors AA, et al. Treating oxidative stress in heart failure: past, present, and future. Eur J Heart Fail. 2018;21:425-435. http://doi.org/ 10.1002/ejhf.1320
Tsutsui H, Kinugawa S, and Matsushima S. Oxidative stress and heart failure. Am J Physiol Heart Circ. 2011;301:2181-2190.
Sarhene M, Wang Y, Wei J, et al. Biomarkers in heart failure: the past, current, and future. Heart Fail Rev. 2019;24:867-903. https://doi.org/10.1007/s10741-019-09807-z
Niriayo YL, Asgedom SW, Demoz GT, et al. Treatment optimization of beta blockers in chronic heart failure therapy. Nature. 2020;10: 1-8. https://doi.org/10.1038/s41598-020-72836-4
Viera JL and Mehra MR. Heart failure. In: Bhatt DL. Opie’s cardiovascular drugs. Philadelphia: Elsevier; 2021:147-230.
Nakamura K, Murakami M, Miura D, et al. Beta blockers and oxidative stress in patients with heart failure. Pharmaceuticals. 2011;4:1088-1100. https://doi.org/10.3390%2Fph4081088
Selles MM, Datino T, Alhama M, et al. Rapid carvedilol up-titration in hospitalized patients with left ventricular systolic dysfunction - data from the carvedilol in hospital. J Cardiovasc Med. 2010;11: 352-358. https://doi.org/10.2459/jcm.0b013e328334f48b
Arifianto H. Effect of Carvedilol Rapid Up Titration in Patients with Heart Failure with Reduced Ejection Fraction. 2022 https://clinicaltrials.gov/ct2/show/NCT05179070
Dahlan SM. Statistik deskriptif, bivariat, dan multivariat. In: Dahlan SM. Statistik untuk Kedokteran dan Kesehatan. Jakarta: Salemba Medika; 2013:2-49.
Masarone D, Martucci ML, Errigo V, et al. The use of B-blockers in heart failure with reduced ejection fraction. J Cardiovasc Dev Dis. 2021;8:1-11. https://doi.org/10.3390/jcdd8090101
McDonagh TA, Metra M, Adamo M, et al. Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;1-128. https://doi.org/10.1093/eurheartj/ehab368
Ouwerkerk W, Voors AA, Anker SD, et al. Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study. Eur Heart J; 2017;38:1883-1890. https://doi.org/10.1093/eurheartj/ehx026
Kumar M, Agrawal BK, Mishra A, et al. A comparative study of MDA level as a marker of oxidative stress in hypertensive patients and controls. Int J Med Sci Diag Res. 2020;9: 3-5. http://dx.doi.org/10.32553/ijmsdr.v4i9.669
Sunita R, Sahidan S, Hidayat, R, et al. Evaluation of malondialdehyde in type 2 diabetes mellitus patients as oxidative stress markers in Bengkulu population. Bioscientia Medicina. 2020;3: 45-54. https://doi.org/10.32539/bsm.v4i3.146
Reza JZ, Shahmoradi H, Mohammadyari, et al. Evaluation of malondialdehyde in type 2 diabetic patients with coronary artery disease. J Bio Today World. 2014;6: 129-132.
Negreva M, Georgiev S, Penev A, et al. Dynamics of oxidative status in patients with paroxysmal atrial fibrillation. Scr Sci Med. 2014;3:33-41. http://dx.doi.org/10.14748/ssm.v46i3.764
Shah AA, Khand F, and Khand TU. Effect of smoking on serum xanthine oxidase, malondialdehyde, ascorbic acid, and a tocopherol levels in healthy male subjects. Pak J Med Sci. 2015;1: 146-149. https://doi.org/10.12669%2Fpjms.311.6148
Singh UN, Kumar S, and Dhakal S. Study of oxidative stress in hypercholesterolemia. Int J Contemp Med. 2017;4: 1204-1207.
Olia JBH, Ansari MHK, Rasmi Y, et al. Evaluation of malondialdehyde level and total antioxidant capacity in patients with hyperthyroidism. Int J Res Med Sci; 2019;2:121-127.
Castro P, Perez O, Greig D, et al. Effects of Carvedilol on functional capacity, left ventricular function, catecholamines, and oxidative stress in patients with chronic heart failure. Rev Esp Cardiol; 2004;11:1053-1058.
Faragli A, Tano GD, Carlini CD, et al. In hospital heart rate reduction with beta blockers and ivabradine early after recovery in patients with acute decompensated heart failure reduces short term mortality and rehospitalization. Front Cardiovasc Med; 2021;8: 1-10. https://doi.org/10.3389/fcvm.2021.665202

[1] Pol AV, Gilst WH, Voors AA, et al. Treating oxidative stress in heart failure: past, present, and future. Eur J Heart Fail. 2018;21:425-435. http://doi.org/ 10.1002/ejhf.1320

[2] Tsutsui H, Kinugawa S, and Matsushima S. Oxidative stress and heart failure. Am J Physiol Heart Circ. 2011;301:2181-2190.

[3] Sarhene M, Wang Y, Wei J, et al. Biomarkers in heart failure: the past, current, and future. Heart Fail Rev. 2019;24:867-903. https://doi.org/10.1007/s10741-019-09807-z

[4] Niriayo YL, Asgedom SW, Demoz GT, et al. Treatment optimization of beta blockers in chronic heart failure therapy. Nature. 2020;10: 1-8. https://doi.org/10.1038/s41598-020-72836-4

[5] Viera JL and Mehra MR. Heart failure. In: Bhatt DL. Opie’s cardiovascular drugs. Philadelphia: Elsevier; 2021:147-230.

[6] Nakamura K, Murakami M, Miura D, et al. Beta blockers and oxidative stress in patients with heart failure. Pharmaceuticals. 2011;4:1088-1100. https://doi.org/10.3390%2Fph4081088

[7] Selles MM, Datino T, Alhama M, et al. Rapid carvedilol up-titration in hospitalized patients with left ventricular systolic dysfunction - data from the carvedilol in hospital. J Cardiovasc Med. 2010;11: 352-358. https://doi.org/10.2459/jcm.0b013e328334f48b

[8] Arifianto H. Effect of Carvedilol Rapid Up Titration in Patients with Heart Failure with Reduced Ejection Fraction. 2022 https://clinicaltrials.gov/ct2/show/NCT05179070

[9] Dahlan SM. Statistik deskriptif, bivariat, dan multivariat. In: Dahlan SM. Statistik untuk Kedokteran dan Kesehatan. Jakarta: Salemba Medika; 2013:2-49.

[10] Masarone D, Martucci ML, Errigo V, et al. The use of B-blockers in heart failure with reduced ejection fraction. J Cardiovasc Dev Dis. 2021;8:1-11. https://doi.org/10.3390/jcdd8090101

[11] McDonagh TA, Metra M, Adamo M, et al. Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;1-128. https://doi.org/10.1093/eurheartj/ehab368

[12] Ouwerkerk W, Voors AA, Anker SD, et al. Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study. Eur Heart J; 2017;38:1883-1890. https://doi.org/10.1093/eurheartj/ehx026

[13] Kumar M, Agrawal BK, Mishra A, et al. A comparative study of MDA level as a marker of oxidative stress in hypertensive patients and controls. Int J Med Sci Diag Res. 2020;9: 3-5. http://dx.doi.org/10.32553/ijmsdr.v4i9.669

[14] Sunita R, Sahidan S, Hidayat, R, et al. Evaluation of malondialdehyde in type 2 diabetes mellitus patients as oxidative stress markers in Bengkulu population. Bioscientia Medicina. 2020;3: 45-54. https://doi.org/10.32539/bsm.v4i3.146

[15] Reza JZ, Shahmoradi H, Mohammadyari, et al. Evaluation of malondialdehyde in type 2 diabetic patients with coronary artery disease. J Bio Today World. 2014;6: 129-132.

[16] Negreva M, Georgiev S, Penev A, et al. Dynamics of oxidative status in patients with paroxysmal atrial fibrillation. Scr Sci Med. 2014;3:33-41. http://dx.doi.org/10.14748/ssm.v46i3.764

[17] Shah AA, Khand F, and Khand TU. Effect of smoking on serum xanthine oxidase, malondialdehyde, ascorbic acid, and a tocopherol levels in healthy male subjects. Pak J Med Sci. 2015;1: 146-149. https://doi.org/10.12669%2Fpjms.311.6148

[18] Singh UN, Kumar S, and Dhakal S. Study of oxidative stress in hypercholesterolemia. Int J Contemp Med. 2017;4: 1204-1207.

[19] Olia JBH, Ansari MHK, Rasmi Y, et al. Evaluation of malondialdehyde level and total antioxidant capacity in patients with hyperthyroidism. Int J Res Med Sci; 2019;2:121-127.

[20] Castro P, Perez O, Greig D, et al. Effects of Carvedilol on functional capacity, left ventricular function, catecholamines, and oxidative stress in patients with chronic heart failure. Rev Esp Cardiol; 2004;11:1053-1058.

[21] Faragli A, Tano GD, Carlini CD, et al. In hospital heart rate reduction with beta blockers and ivabradine early after recovery in patients with acute decompensated heart failure reduces short term mortality and rehospitalization. Front Cardiovasc Med; 2021;8: 1-10. https://doi.org/10.3389/fcvm.2021.665202

Effect of carvedilol rapid up-titration on malondialdehyde levels in patient with heart failure reduced ejection fraction

Abstract

References

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