Vasodilatator Beta Blockers in Cardiovascular Disease

Abstract

Beta adrenergic agonists (β-blockers) have proven effects in cardiovascular area. However, their usage as first-line treatment had started to be questioned recently due to their side effects, mainly systemic hypertension. Therefore, third generation agents with less side effects and more β1 selectivity have started to be used in clinical cardiology in the last decades. Although these agents were targeted to be used for the treatment of chronic heart failure at the begining, they have started to be used as the first-line treatment for some other indications, mainly for hypertension, as they have a good efficacy and tolerability profile and have less metabolic side effects. In this article, vasodilatator β-blockers were reviewed in detail with the guidance of clinical trials performed in this area. Beta adrenerjik agonistler (β-blokerler), kardiyovasküler alanda etkinliğini kanıtlamış ajanlardır. Bununla birlikte, son dönemde başta sistemik hipertansiyon olmak üzere yan etki profilleri nedeniyle ilk basamak tedavide kullanımları sorgulanmaktadır. Bu temel altında klinik kardiyolojide son birkaç dekat içerisinde yan etkileri azaltılmış, β1 selektiviteleri artırılan üçüncü kuşak ajanlar klinik kullanılma girmiştir. Bu ajanların erken dönem klinik çalışmaları kronik kalp yetersizliği üzerine iken, artan etkinlikleri, tolerabiliteleri ve düşük metabolik yan etkileriyle, özelikle hipertansiyon olmak üzere, tekrar ilk basamak tedavideki yerlerini almaya başlamışlardır. Bu makalede vazodilatatör β-blokerler, klinik çalışmaları kılavuzluğunda gözden geçirilmiştir.

Keywords

• β-blocker, vasodilatator

Kardiyovasküler Hastalıklarda Vazodilatatör Beta Blokerler

Öz

Beta adrenerjik agonistler (β-blokerler), kardiyovasküler alanda etkinliğini kanıtlamış ajanlardır. Bununla birlikte, son dönemde başta sistemik hipertansiyon olmak üzere yan etki profilleri nedeniyle ilk basamak tedavide kullanımları sorgulanmaktadır. Bu temel altında klinik kardiyolojide son birkaç dekat içerisinde yan etkileri azaltılmış, β1 selektiviteleri artırılan üçüncü kuşak ajanlar klinik kullanılma girmiştir. Bu ajanların erken dönem klinik çalışmaları kronik kalp yetersizliği üzerine iken, artan etkinlikleri, tolerabiliteleri ve düşük metabolik yan etkileriyle, özelikle hipertansiyon olmak üzere, tekrar ilk basamak tedavideki yerlerini almaya başlamışlardır. Bu makalede vazodilatatör β-blokerler, klinik çalışmaları kılavuzluğunda gözden geçirilmiştir.

Anahtar Kelimeler

• β-bloker, vazodilatatör.

Kaynakça

1. Cruickshank JM, Prichard BNC. Beta-blockers in clinical practice. London: Churchill Livingstone; 1996.
2. Tamargo J, Delpón E. Optimization of [beta]-blockers' pharmacology. J Cardiovasc Pharmacology 1990;16(Suppl 5):S10-S18.
3. Frishman WH, Lazar EJ, Gorodokin G. Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents. Clin Pharmacokinet 1991;20:311-8.
4. Frishman WH. Carvedilol. N Engl J Med 1998;339:1759-65.
5. Benfield P, Sorkin EM. Esmolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1987;33:392-412.
6. Kjekshus J, Gilpin E, Cali G, Blackey AR, Henning H, Ross J Jr. Diabetic patients and beta-blockers after acute myocar- dial infarction. Eur Heart J 1990;11:43-50.
7. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998;339:489-97.
8. Poole-Wilson P. COMET study. European Congress of Cardiology. Vienna, September 2003.

9. von Arnim T. Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine. The TIBBS Investigators. J Am Coll Cardiol 1995;25:231-8.
10. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-90.
11. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996;334:1349-55.
12. Randomised, placebo-controlled trial of carvedilol in pati- ents with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet 1997;349:375-80.
13. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9-13.
14. Effect of metoprolol CR/XL in chronic heart failu- re: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7.
15. Effects of metoprolol CR in patients with ischemic and dila- ted cardiomyopathy : the randomized evaluation of strate- gies for left ventricular dysfunction pilot study. Circulation 2000;101:378-84.
16. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.
17. Doughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. J Am Coll Cardiol 1997;29:1060-6.
18. Goldstein S, Fagerberg B, Hjalmarson A, Kjekshus J, Waagstein F, Wedel H, et al. Metoprolol controlled relea- se/extended release in patients with severe heart failure: analysis of the experience in the MERIT-HF study. J Am Coll Cardiol 2001;38:932-8.
19. Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344:1659-67.
20. Torp-Pedersen C, Kİber L, Ball S, Hall A, Brendorp B, Ottesen M, et al. The incomplete bucindolol evaluation in acute myocardial infarction Trial (BEAT). Eur J Heart Fail 2002;4:495-9.
21. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7-13.
22. Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, et al. Randomized trial to deter- mine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215-25.