Sartans in hypertension treatment: advantages of candesartan use

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Abstract

Aim. To present a scientific review of angiotensin II (AT II) receptor blockers (sartans) clinical pharmacology, in particular pharmacologic and clinical characteristics of candesartan. Materials and methods. A literature search for Russian and foreign publications since year 1999 was conducted in Russian and international databases (PubMed, eLibrary and others) in order to write this review. Results. In the last years AT II receptor blockers or sartans have been widely used for arterial hypertension treatment. Despite general characteristics of this antihypertensive medications group such as mechanism of action, possibility of administration one time a day, good tolerance, and minimal adverse effects, there are clinical and pharmacological differences between medications that determine their effectiveness. It is shown that candesartan kinetics of interaction with AT receptors is specific, that results in more expressed hypotensive effect and high trough/peak index of hypotensive effect. Candesartan pharmacokinetics and hypotensive effect do not depend on CYP2C9 metabolizing ferment genetic polymorphism. According to several metaanalyses results candesartan has advantages in level of blood pressure (BP) decrease that results in BP-dependent advantages. In a large observational study candesartan showed better results of influence on arterial hypertension cardiovascular outcomes in comparison with losartan, that demonstrates possible BP-independent clinical and pharmacological advantages. At present sartan therapy is becoming more affordable because of generics development. Hyposart (manufacturer - pharmaceutical company Polpharma, Poland) has an acknowledged place among candesartan generics. It has shown complete equivalence to original medication in bioequivalence studies, what is important in evidence-based medicine. Conclusion. Candesartan is one of the most powerful medications of AT II receptor blockers group that is proved by its clinical and pharmacological characteristics. Advantages of its hypotensive effect and long-term effectiveness were demonstrated in several studies and metaanalyses and are associated with BP-dependent and BP-independent effects determined by receptor interaction characteristics.

About the authors

Marina V. Leonova

Interregional Public Organization “Association of Clinical Pharmacologists in Russia”

Email: anti23@mail.ru
Corr. Memb. of RANS, D. Sci. (Med.), Prof., clinical pharmacologist, Member

References

  1. Turnbull F. Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362 (9395): 1527-35.
  2. Law M.R, Morris J.K, Wald N.J. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.
  3. Ettehad D, Emdin C.A, Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387 (10022): 957-67.
  4. ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 39: 3021-104.
  5. Vauquelin G, Fierens F, Van Liefde I. Long-lasting angiotensin type 1 receptor binding and protection by candesartan: comparison with other biphenyl-tetrazole sartans. J Hypertens 2006; 24 (Suppl. 1): S23-S30.
  6. Van Liefde I, Vauquelin G. Sartan - AT1 receptor interactions: In vitro evidence for insurmountable antagonism and inverse agonism. Mol Cell Endocrinol 2009; 302 (2): 237-43.
  7. Michel M.C, Foster C, Brunner H.R, Liu L. A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists. Pharmacol Rev 2013; 65: 809-48.
  8. Conlin P.R. Angiotensin II antagonists in the treatment of hypertension: more similarities than differences. J Clin Hypertens (Greenwich) 2000; 2 (4): 253-57.
  9. Heran B.S, Wong M.M.Y, Heran I.K, Wright J.M. Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. Cochrane Database Sys Rev 2008; 4: CD003822.
  10. Zheng Z, Shi H, Jia J et al. A systematic review and meta-analysis of candesartan and losartan in the management of essential hypertension. J Renin Angiotensin Aldosterone Syst 2011; 12 (3): 365-74.
  11. Lewington S, Clarke R, Qizilbash N et al; Prospective Studies Collaboration. Age-specific relevance of usual BP to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 14: 1903-13.
  12. Paz M.A, de-La-Sierra A, Sáez M et al. Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine (Baltimore) 2016; 95 (30): e4071.
  13. Meredith P.A, Elliott H.L. FDA guidelines on trough: peak ratios in the evaluation of antihypertensive agents. J Cardiovasc Pharmacol 1994; 23 (Suppl. 5): S26-S30.
  14. Сидоренко Б.А., Преображенский Д.В., Соплевенко А.В. и др. Кандесартан - новый блокатор АТ1-ангиотензивновых рецепторов: особенности фармакологии и опыт использования при артериальной гипертензии. Кардиология. 2004; 1: 55-65. .
  15. Lacourciere Y, Asmar R. for the Candesartan/Losartan study investigators. A Comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Am J Hypertens 1999; 12: 1181-7.
  16. Wang B, Wang J, Huang S-Q et al. Genetic Polymorphism of the Human Cytochrome P450 2C9 Gene and Its Clinical Significance. Cur Drug Metab 2009; 10: 781-834.
  17. Israili Z.H. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens 2000; 14 (Suppl. 1): S73-S86.
  18. Yasar U, Forslund-Bergengren C, Tybring G et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther 2002; 71 (1): 89-98.
  19. Hong X, Zhang S, Mao G et al. CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population. Eur J Clin Pharmacol 2005; 61 (9): 627-34.
  20. Hallberg P, Karlsson J, Kurland L et al. The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. J Hypertens 2002; 20 (10): 2089-93.
  21. Hanatani T, Fukuda T, Ikeda M et al. CYP2C9*3 influences the metabolism and the drug-interaction of candesartan in vitro. Pharmacogenomics 2001; 1: 288-92.
  22. Cabaleiro T, Román M, Ochoa D et al. Evaluation of the Relationship between Sex, Polymorphisms in CYP2C8 and CYP2C9, and Pharmacokinetics of Angiotensin Receptor Blockers. Drug Metab Dispos 2013; 41: 224-9.
  23. Kjeldsen S.E, Stalhammar J, Hasvold P et al. Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension. J Hum Hypertens 2010; 24: 263-73.
  24. Russell D, Stålhammar J, Bodegard J et al. Cardiovascular events in subgroups of patients during primary treatment of hypertension with candesartan or losartan. J Clin Hypertens (Greenwich) 2011; 13 (3): 189-97.
  25. Отчет о результатах исследования CNDN-01 «Открытое, рандомизированное, перекрестное исследование сравнительной фармакокинетики и биоэквивалентности препаратов Гипосарт, таблетки 32 мг, Фармацевтический завод "Польфарма" АО (Польша), и Атаканд®, таблетки 32 мг, "АстраЗенека АБ" (Швеция), с участием здоровых добровольцев». М., 2013.

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