Wiederherstellung und Aufrechterhaltung
eines Sinusrhythmus bei Patienten mit Vorhofflimmern
Neue medikamentöse TherapieansätzeConversion and maintenance of sinus rhythm
in patients with atrial fibrillation – new pharmacological
approachesNew pharmacological
approachesS. Runge1
, R. Dietz1
, W. Haverkamp1
1Medizinische Klinik Schwerpunkt Kardiologie,
Campus Virchow-Klinikum und Campus Berlin-Buch, Berlin
Die Therapie des Vorhofflimmerns, der häufigsten Herzrhythmusstörung
im Erwachsenenalter, stellt zusammen mit der altersabhängigen
steigenden Prävalenz in einer zunehmend alternden Gesellschaft
eine wachsende Herausforderung dar. Aktuelle medikamentöse
Therapieansätze zur Wiederherstellung und Erhaltung eines
Sinusrhythmus werden durch die begrenzte Effektivität,
Tolerabilität und Sicherheit der bisher eingesetzten Antiarrhythmika
eingeschränkt. Ein primäres Ziel ist somit die
Entwicklung von wirkungsvollen Medikamenten mit möglichst
geringem Nebenwirkungsprofil Die folgende Übersicht beschreibt
neue vielversprechende medikamentöse Therapieansätze,
die die bislang bestehenden Probleme und Grenzen der Antiarrhtmika,
zumindest partiell, überwinden.
Summary
Atrial fibrillation is the most frequent cardiac arrthythmia
in adults and its prevalence is increasing with age. Therefore,
the importance of an adequate therapy is an increasing challenge,
in particular considering the demographic shift towards an aging
population. Current antiarrhythmic drug therapies for the conversion
of atrial fibrillation and the maintenance of sinus rhythm are limited
by efficacy, tolerance and safety of the currently available agents.
Therefore, a primary goal is to develop effective antiarrhythmic drugs
with as little as possible side effects. The following review describes
new promising drug therapy approaches to atrial fibrillation that
may overcome some of the limitations of current therapies.
Schlüsselwörter
Vorhofflimmern - Antiarrhythmika - neue Therapieansätze - Ionenkanäle - Vorhofspezifische Wirkstoffe - Sinusrhythmus - Torsades de pointes
Keywords
atrial fibrillation - antiarrhythmic drugs - new therapies - ion channels - atrial specific agents - sinus rhythm - torsades de pointes
Literatur
1
Stroke Prevention in
Atrial Fibrillation Study. Final results.
Circulation.
1991;
84
(2)
527-539
3
Calo L, Bianconi L, Colivicchi F. 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
(10)
1723-1728
4
Dale K M, White C M.
Dronedarone:
an amiodarone analog for the treatment of atrial fibrillation and
atrial flutter.
Ann Pharmacother.
2007;
41
(4)
599-605
5
Deedwania P C, Singh B N, Ellenbogen K. et al .
Spontaneous conversion and maintenance
of sinus rhythm by amiodarone in patients with heart failure and
atrial fibrillation: observations from the veterans affairs congestive
heart failure survival trial of antiarrhythmic therapy (CHF-STAT).
The Department of Veterans Affairs CHF-STAT Investigators.
Circulation.
1998;
98
(23)
2574-2579
6
Ehrlich J R, Biliczki P, Hohnloser S H, Nattel S.
Atrial-selective
approaches for the treatment of atrial fibrillation.
J
Am Coll Cardiol.
2008;
51
(8)
787-792
7
Ehrlich J R, Hohnloser S H, Nattel S.
Role of angiotensin system and effects of its inhibition in
atrial fibrillation: clinical and experimental evidence.
Eur
Heart J.
2006;
27
(5)
512-518
8
Fauchier L, Pierre B, de Labriolle A. et al .
Antiarrhythmic effect of statin therapy
and atrial fibrillation a meta-analysis of randomized controlled
trials.
J Am Coll Cardiol.
2008;
51
(8)
828-835
9
Fuster V, Ryden L E, Cannom D S. et al .
ACC/AHA/ESC
2006 guidelines for the management of patients with atrial fibrillation – executive
summary: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing
Committee to Revise the 2001 Guidelines for the Management of Patients
With Atrial Fibrillation).
J Am Coll Cardiol.
2006;
48
(4)
854-906
10
Gautier P, Guillemare E, Djandjighian L. et al .
In vivo and in vitro characterization of
the novel antiarrhythmic agent SSR149744C: electrophysiological,
anti-adrenergic, and anti-angiotensin II effects.
J Cardiovasc
Pharmacol.
2004;
44
(2)
244-257
11
Gautier P, Serre M, Cosnier-Pucheu S. et al .
In vivo and in vitro antiarrhythmic effects
of SSR149744C in animal models of atrial fibrillation and ventricular
arrhythmias.
J Cardiovasc Pharmacol.
2005;
45
(2)
125-135
12 Gerth A, Höss J, Näbauer M, Steinbeck G. Epidemiologie
von Vorhofflimmern. In: Lewalter T, editor Rationale
Arrhythmiebehandlung – Ein Paradigmenwechsel. Darmstadt; Steinkopff 2006: 13-22
14
Goldschlager N, Epstein A E, Naccarelli G V. et al .
A practical guide
for clinicians who treat patients with amiodarone: 2007.
Heart
Rhythm.
2007;
4
(9)
1250-1259
16
Healey J S, Baranchuk A, Crystal E. et al .
Prevention of atrial fibrillation with
angiotensin-converting enzyme inhibitors and angiotensin receptor
blockers: a meta-analysis.
J Am Coll Cardiol.
2005;
45
(11)
1832-1839
17
Hohnloser S H, Kuck K H, Lilienthal J.
Rhythm or rate control in atrial fibrillation--Pharmacological
Intervention in Atrial Fibrillation (PIAF): a randomised trial.
Lancet.
2000;
356
(9244)
1789-1794
18
Humphries K H, Lee M, Sheldon R. et
al .
Statin use and recurrence of atrial fibrillation
after successful cardioversion.
Am Heart J.
2007;
154
(5)
908-913
19
Kjolbye A L, Haugan K, Hennan J K, Petersen J S.
Pharmacological
modulation of gap junction function with the novel compound rotigaptide:
a promising new principle for prevention of arrhythmias.
Basic Clin
Pharmacol Toxicol.
2007;
101
(4)
215-230
20
Kowey P R, Aliot E M, Capucci A. et al .
Placebo-controlled double-blind dose-ranging
study of the efficacy and safety of SSR149744C in patients with
recent atrial fibrillation/flutter. (Abstract).
Heart
Rhythm.
2007;
4
S72
21
Lee K W, Everett T H, Rahmutula D. et al .
Pirfenidone prevents the development of
a vulnerable substrate for atrial fibrillation in a canine model
of heart failure.
Circulation.
2006;
114
(16)
1703-1712
23
Maggioni A P, Latini R, Carson P E. et al .
Valsartan reduces the incidence of atrial
fibrillation in patients with heart failure: results from the Valsartan
Heart Failure Trial (Val-HeFT).
Am Heart J.
2005;
149
(3)
548-557
25
Morrow J P, Cannon C P, Reiffel J A.
New antiarrhythmic drugs for establishing
sinus rhythm in atrial fibrillation: what are our therapies likely
to be by 2010 and beyond?.
Am Heart J.
2007;
154
(5)
824-829
27
Patti G, Chello M, Candura D. et
al .
Randomized trial of atorvastatin for reduction
of postoperative atrial fibrillation in patients undergoing cardiac
surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of
MYocardial Dysrhythmia After cardiac surgery) study.
Circulation.
2006;
114
(14)
1455-1461
28
Pedersen O D, 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
(4)
376-380
29
Rahme M M, Cotter B, Leistad E. et al .
Electrophysiological and antiarrhythmic
effects of the atrial selective 5-HT(4) receptor antagonist RS-100 302
in experimental atrial flutter and fibrillation.
Circulation.
1999;
100
(19)
2010-2017
30
Roy D, Pratt C M, Torp-Pedersen C. et al .
Vernakalant hydrochloride for rapid conversion
of atrial fibrillation: a phase 3, randomized, placebo-controlled
trial.
Circulation.
2008;
117
(12)
1518-1525
31
Roy D, Rowe B H, Stiell I G. et al .
A randomized, controlled trial of RSD1235,
a novel anti-arrhythmic agent, in the treatment of recent onset
atrial fibrillation.
J Am Coll Cardiol.
2004;
44
(12)
2355-2361
33
Sablayrolles S, Le Grand B.
Drug evaluation: dronedarone,
a novel non-iodinated anti-arrhythmic agent.
Curr Opin
Investig Drugs.
2006;
7
(9)
842-849
34
Savelieva I, Camm J.
Anti-arrhythmic drug therapy
for atrial fibrillation: current anti-arrhythmic drugs, investigational
agents, and innovative approaches.
Europace.
2008;
10
(6)
647-665
35
Singh B N, Aliot E.
Newer antiarrhythmic agents
for maintaining sinus rhythm in atrial fibrillation: simplicity
or complexity?.
European Heart Journal Supplements.
2007;
9
(Supplement G)
G17-G25
38
Touboul P, Brugada J, Capucci A. et al .
Dronedarone for prevention of atrial fibrillation:
a dose-ranging study.
Eur Heart J.
2003;
24
(16)
1481-1487
39
Van Gelder I C, Hagens V E, Bosker H A. et al .
A comparison of rate control
and rhythm control in patients with recurrent persistent atrial
fibrillation.
N Engl J Med.
2002;
347
(23)
1834-1840
41
Vermes E, Tardif J C, Bourassa M G. et al .
Enalapril decreases the
incidence of atrial fibrillation in patients with left ventricular
dysfunction: insight from the Studies Of Left Ventricular Dysfunction
(SOLVD) trials.
Circulation.
2003;
107
(23)
2926-2931
43
Waldo A L, Camm A J, deRuyter H. et al .
Effect of d-sotalol on mortality in patients
with left ventricular dysfunction after recent and remote myocardial
infarction. The SWORD Investigators. Survival With Oral d-Sotalol.
Lancet.
1996;
348
(9019)
7-12
44
Wyse D G, Waldo A L, DiMarco J P. et al .
A comparison of rate control and
rhythm control in patients with atrial fibrillation.
N
Engl J Med.
2002;
347
(23)
1825-1833
45
Yin Y, Dalal D, Liu Z. et
al .
Prospective randomized study comparing amiodarone
vs. amiodarone plus losartan vs. amiodarone plus perindopril for the
prevention of atrial fibrillation recurrence in patients with lone
paroxysmal atrial fibrillation.
Eur Heart J.
2006;
27
(15)
1841-1846
