Atriyum Fibrilasyonunun İlaç Tedavisindeki Yenilikler

Yıl 2015, Cilt: 18 Sayı: 3, 139 - 145, 01.12.2015

Yusuf Türkmen Cengizhan Türkoğlu Mustafa Yıldız

Öz

Atriyum
fibrilasyonu (AF) klinikte en sık görülen aritmi cinsidir. Hastalara getirdiği
sağlık sorunları ve mortalite yanı sıra komplikasyonları ekonomik kayıplara
neden olmaktadır. Sağlık sorunlarının başında serebrovasküler ve
kardiyovasküler hastalıklar gelmektedir. Dolayısıyla AF’li hastaların ritmini yeniden
sinüs ritmine döndürmek ve tromboembolik olaylara karşı etkin koruma sağlamak
oldukça önemlidir. Bu amaçla, günümüzde kullanılmakta olan ritim düzenleyici ve
pıhtı oluşumunu önleyici ilaçlar söz konusu ise de, bunlardan elde edilen
yararlar ve kullanım kolaylığı istendiği düzeyde değildir. Hem antiaritmik
ilaçların yan etkileri hem de antikoagülanların dar terapatik sınırları olması
nedeniyle, AF tedavisinde yeni ilaçlara gereksinim duyulmaktadır. Bu amaçla
birçok ilacın AF üzerindeki etkileri araştırılmaktadır. Bu derlemede AF’nin
ilaç tedavisindeki yenilikler ele alınmıştır.

Anahtar Kelimeler

Atriyal fibrilasyon, yeni ilaçlar

Novel Medications in the Treatment of Atrium Fibrillation

Öz

Atrial
fibrillation (AF) is the most commonly encountered arrhythmia. Besides serious
health problems and mortality incurred by patients, its complitacions bring
about substantial economical losses. Among the most important health-related
consequences are cerebrovascular and cardiovascular diseases. Therefore,
convertion of AF to sinus rhythm and effective prevention from thromboembolic
events are of particular importance. Despite the current availability of many
rhythm control and anticoagulant medications, their efficacy and accessibility
are not at a desired level. Due to adverse effects of antiarrhythmic drugs and
narrow therapeutic range of anticoagulant drugs, there have been an increasing
need for novel medications. There is ongoing research on the effects of many
madications on AF. This paper reviews novel medicaitons in AF treatment.

Anahtar Kelimeler

Atrial fibrillation, novel drugs

Kaynakça

• 1. Uyarel H, Onat A, Yüksel H, Can G, Ordu S, Dursunoğlu D. Türk halkında kronik atriyal fibrilasyon insidansı, prevalansı ve mortalitesine ilişkin tahminler. Türk Kardiyol Dern Arş 2008;36:214-22.
• 2. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationship between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004;109:1509-13.
• 3. Knobloch K, Brendel J, Rosenstein B, Bleich M, Busch AE, Wirth KJ. Atrial-selective antiarrhythmic actions of novel Ikur vs. Ikr, Iks, and IKAch class Ic drugs and beta blockers in pigs. Med Sci Monit 2004;10BR221-8.
• 4. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-66.
• 5. El-Armouche A, Boknik P, Eschenhagen T, Carrier L, Knaut M, Ravens U, et al. Molecular determinants of altered Ca2+ handling in human chronic atrial fibrillation. Circulation 2006;114:670-80.
• 6. Blaauw Y, Gögelein H, Tieleman RG, van Hunnik A, Schotten U, Allessie MA. “Early” class III drugs for the treatment of atrial fibrillation: efficacy and atrial selectivity of AVE0118 in remodeled atria of the goat. Circulation 2004;110:1717-24.
• 7. Bosch RF, Nattel S. Cellular electrophysiology of atrial fibrillation. Cardiovasc Res 2002;54:259-69.
• 8. Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S. Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 1999;84:776-84.
• 9. Courtemanche M, Ramirez RJ, Nattel S. Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: insights from a mathematical model. Cardiovasc Res 1999;42:477-89.
• 10. Peukert S, Brendel J, Pirard B, Strübing C, Kleemann HW, Böhme T, et al. Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel. Bioorg Med Chem Lett 2004;14:2823-7.
• 11. Matsuda T, Masumiya H, Tanaka N, Yamashita T, Tsuruzoe N, Tanaka Y, et al. Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K+ channel Kv1.5 current. Life Sci 2001;68:2017-24.
• 12. Gögelein H, Brendel J, Steinmeyer K, Strübing C, Picard N, Rampe D, et al. Effects of the atrial antiarrhythmic drug AVE0118 on cardiac ion channels. Naunyn Schmiedebergs Arch Pharmacol 2004;370:183-92.
• 13. Du YM, Zhang XX, Tu DN, Zhao N, Liu YJ, Xiao H, et al. Molecular determinants of Kv1.5 channel block by diphenyl phosphine oxide-1. J Mol Cell Cardiol 2010;48:1111-20.
• 14. Bilodeau MT, Trotter BW. Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology. Curr Top Med Chem 2009;9:436-51.
• 15. Wirth KJ, Paehler T, Rosenstein B, Knobloch K, Maier T, Frenzel J, et al. Atrial effects of the novel K(+)-channel-blocker AVE0118 in anesthetized pigs. Cardiovasc Res 2003;60:298-306.
• 16. Wettwer E, Hála O, Christ T, Heubach JF, Dobrev D, Knaut M, et al. Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation. Circulation 2004;110:2299-306.
• 17. Rivard L, Shiroshita-Takeshita A, Maltais C, Ford J, Pinnock R, Madge D, at al. Electrophysiological and atrial antiarrhythmic effects of a novel IKur/Kv1.5 blocker in dogs. Heart Rhythm 2005;2(Suppl):S180.
• 18. Shiroshita-Takeshita A, Maltais C, Ford J, Madge D, Pinnock R, Nattel S. Electrophysiological and atrial antiarrhythmic effects of a novel IKur/Kv1.5 blocker in dogs with atrial tachycardia remodeling. Heart Rhythm 2006;3(Suppl):S183.
• 19. Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415:219-26.
• 20. Hashimoto N, Yamashita T, Tsuruzoe N. Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation. Pharmacol Res 2006;54:136-41.
• 21. Duggan ST, Scott LJ. Intravenous vernakalant: a review of its use in the management of recent-onset atrial fibrillation. Drugs 2011;71:237-52.
• 22. Camm AJ, Capucci A, Hohnloser SH, Torp-Pedersen C, Van Gelder IC, Mangal B, et al. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol 2011;57:313-21.
• 23. Naccarelli GV, Wolbrette DL, Samii S, Banchs JE, Penny-Peterson E, Stevenson R, Gonzalez MD. Vernakalant: pharmacology electrophysiology, safety and efficacy. Drugs 2008;44:325-9.
• 24. Roy D, Pratt CM, Torp-Pedersen C, Wyse DG, Toft E, Juul-Moller S, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation 2008;117:1518-25.
• 25. Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007;357:987-99.
• 26. Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am Heart J 2008;156:527.e1-9.
• 27. Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol 2010;21:597-605.
• 28. Pogge EK, Haber SL. Elevated international normalized ratio associated with use of dronedarone and warfarin. Ann Pharmacother 2011;45:e46.
• 29. Hohnloser SH, Dorian P, Straub M, Beckmann K, Kowey P. Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter. Am J Cardiol 2004;44:99-104.
• 30. Krishnamoorthy S, Lip GY. Novel antiarrhythmic drugs in atrial fibrillation: focus on tedisamil. Expert Opin Investig Drugs 2009;18:1191-6.
• 31. Shiroshita-Takeshita A, Sakabe M, Haugan K, Hennan JK, Nattel S. Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs. Circulation 2007;115:310-8.
• 32. Macia E, Dolmatova E, Cabo C, Sosinsky AZ, Dun W, Coromilas J, et al. Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide. Circ Arrhythm Electrophysiol 2011;4:344-51.
• 33. Pederson OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999;100:376-80.
• 34. Madrid AH, Bueno MG, Rebollo JM, Marín I, Peña G, Bernal E, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002;106:331-6.
• 35. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005;45:1243-8.
• 36. Ozaydın M, Varol E, Aslan SM, Küçüktepe Z, Doğan A, Özturk M, et al. Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion. Am J Cardiol 2006;97:1490-3.
• 37. Siu CW, Lau CP, Tse HF. Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion. Am J Cardiol 2003;92:1343-5.
• 38. Mozaffarian D, Psaty BM, Rimm EB, Lemaitre RN, Burke GL, Lyles MF, et al. Fish intake and risk of incident atrial fibrillation. Circulation 2004;110:368-73.
• 39. Calò L, Bianconi L, Colivicchi F, Lamberti F, Loricchio ML, de Ruvo E, et al. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol 2005;45:1723-8.
• 40. Burashnikov A, Petroski A, Hu D, Barajas-Martinez H, Antzelevitch C. Atrial-selective inhibition of sodium channel current by Wenxin Keli is effective in suppressing atrial fibrillation. Heart Rhythm 2012;9:125-31.
• 41. Eriksson BI, Dahl OE, Ahnfelt L, Kälebo P, Stangier J, Nehmiz G, et al. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost 2004;2:1573-80.
• 42. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51.
• 43. Eikelboom JW, O’Donnell M, Yusuf S, Diaz R, Flaker G, Hart R, et al. Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment. Am Heart J 2010;159:348-353.e1.
• 44. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92.
• 45. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91.
• 46. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75.
• 47. Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010;104:633-41.
• 48. Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H, Davidson BL, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008;371:315-21.
• 49. Stewart RA. Clinical trials of direct thrombin and factor Xa inhibitors in atrial fibrillation. Curr Opin Cardiol 2011;26:294-9.