Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?

被引:30
作者
Ehrlich, Joachim R. [1 ]
Nattel, Stanley [2 ,3 ]
机构
[1] Goethe Univ Frankfurt, Div Cardiol, Sect Clin Electrophysiol, D-60590 Frankfurt, Germany
[2] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada
[3] Univ Montreal, Montreal, PQ, Canada
基金
加拿大健康研究院;
关键词
antiarrhythmia agents; atrium; electrophysiology; fibrillation; potassium current; ANTIARRHYTHMIC COMPOUND AVE1231; SODIUM-CHANNEL BLOCK; POTASSIUM CURRENT; VERNAKALANT RSD1235; MATHEMATICAL-MODEL; CONTROLLED-TRIAL; RHYTHM CONTROL; HEART-FAILURE; IKACH BLOCKER; SINUS RHYTHM;
D O I
10.1097/HCO.0b013e32831bc336
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Rhythm control remains of therapeutic value for many atrial fibrillation patients despite no evidence of survival benefit. This lack of benefit may relate to side effects of conventional antiarrhythmic drugs. The introduction of novel agents was a logical consequence. Recent findings Novel antiarrhythmics are currently being evaluated in preclinical or clinical studies. Among recently developed drugs, some affect one or more atrial targets, including I-Kur, I-KACh, I-Na or I-SAC, allowing them to act selectively on atria over ventricles. Some drugs that exhibit atrial selectivity have not been successful in preliminary studies. Block of a single atrial-specific target may be insufficient for atrial fibrillation termination and prevention, and multichannel-blocking properties may be a useful alternate approach. Drugs such as vernakalant or ranolazine inhibit multiple channels but display effective and atrial-selective actions. Furthermore, dronedarone, a prototypic multichannel blocker with additional effects on ventricular myocardium, has proven well tolerated and effective in the treatment of atrial fibrillation and may even reduce cardiovascular mortality. Summary Efforts to develop atrial-selective antiarrhythmics are bearing fruit, but such compounds will need to exhibit equal or superior safety and efficacy compared with multichannel blockers such as dronedarone for atrial fibrillation suppression in order to prove their worth. It is still too early to tell whether atrial selectiveness is just hype or truly a hope for antiarrhythmic drug treatment of atrial fibrillation.
引用
收藏
页码:50 / 55
页数:6
相关论文
共 52 条
  • [21] Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent
    Fedida, David
    [J]. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2007, 16 (04) : 519 - 532
  • [22] Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences
    Feng, JL
    Xu, DH
    Wang, ZG
    Nattel, S
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (05): : H1717 - H1725
  • [23] New drugs targeting the cardiac ultra-rapid delayed-rectifier Current(IKur):: Rationale, pharmacology and evidence for potential therapeutic value
    Ford, John W.
    Milnes, James T.
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2008, 52 (02) : 105 - 120
  • [24] Characterization of in vivo and in vitro electrophysiological and antiarrhythmic effects of a novel IKACh blocker, NIP-151:: A comparison with an IKr-Blocker dofetilide
    Hashimoto, Norio
    Yamashita, Toru
    Tsuruzoe, Nobutomo
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2008, 51 (02) : 162 - 169
  • [25] Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation
    Hashimoto, Norio
    Yamashita, Toru
    Tsuruzoe, Nobutomo
    [J]. PHARMACOLOGICAL RESEARCH, 2006, 54 (02) : 136 - 141
  • [26] HOHNLOSER SH, 2008, HEART RHYTHM SOC 200
  • [27] Anti-arrhythmic effects of INa, IKr, and combined IKr-ICaL blockade in an experimental model of acute stretch-related atrial fibrillation
    Kalifa, J.
    Bernard, M.
    Gout, B.
    Bril, A.
    Cozma, D.
    Laurent, P.
    Chalvidan, T.
    Deharo, J. C.
    Djiane, P.
    Cozzone, P.
    Maixent, J. M.
    [J]. CARDIOVASCULAR DRUGS AND THERAPY, 2007, 21 (01) : 47 - 53
  • [28] Mechanisms of atrial fibrillation termination by pure sodium channel blockade in an ionically-realistic mathematical model
    Kneller, J
    Kalifa, J
    Zou, RQ
    Zaitsev, AV
    Warren, M
    Berenfeld, O
    Vigmond, EJ
    Leon, LJ
    Nattel, S
    Jalife, J
    [J]. CIRCULATION RESEARCH, 2005, 96 (05) : E35 - E47
  • [29] Increased mortality after dronedarone therapy for severe heart failure
    Kober, Lars
    Torp-Pedersen, Christian
    McMurray, John J. V.
    Gotzsche, Ole
    Levy, Samuel
    Crijns, Harry
    Amlie, Jan
    Carlsen, Jan
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (25) : 2678 - 2687
  • [30] Long-term safety of a novel antianginal armant in patients with severe chronic stable angina - The Ranolazine Open Label Experience (ROLE)
    Koren, Michael J.
    Crager, Michael R.
    Sweeney, Michael
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (10) : 1027 - 1034