Recent developments in atrial fibrillation
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7485.238 (Published 27 January 2005) Cite this as: BMJ 2005;330:238
Data supplement
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Table A (Posted as supplied by the authors)
Recent and ongoing trials comparing rate and rhythm control strategy.
Study
(year)
n
Follow-up
(years)
Primary End-Point
Result
Rhythm v Rate
p
Hospitalizations
Rhythm v Rate
p
PIAFw1
(2000)
252
1
Symptomatic improvement
55% v 61%
0.317
69% v 24%
0.001
AFFIRMw2
(2002)
4060
3.5
All cause mortality
27% v 17%
0.08
80.% v 73%
<0.001
RACEw3
(2002)
522
2.3
Composite (HF, TE, cardiovascular death, bleeding, adverse drug effects & PPM insertion)
23% v 17%
0.11
---
---
STAFw4
(2003)
200
1.6
Composite (death, stroke, TIA, TE and CPR)
9% v 10%
0.99
54% v 26%
<0.001
HOT CAFÉw5
(2003)
205
1
All cause mortality
1% v 3%
NS
74% v 12%
<0.001
J-RHYTHMw6
(2003)
2600
3
Composite (death, symptomatic cerebral infarction, TE, major bleeding, hospitalizations for HF)
Trial in progress
Table B (Posted as supplied by the authors)
A comparison of novel anticoagulants with conventional warfarin therapy in atrial fibrillation.
Anticoagulant
Route of administration
Dosing regimes
Mechanism of action
Onset of action
Drug/food interaction
Anticoagulation monitoring
Recent/ongoing trials
Warfarin
Oral
Variable,
depending on the INR
Inhibits vitamin K-dependent clotting factors leading to decreased thrombin production
Slow
2-4 days
Many
Yes
The safety and efficacy of warfarin is well established.
Ximelagatran w26
Oral
Fixed daily dose
Direct thrombin (factor IIa) inhibitor
Fast
2 hours
None
No
SPORTIF III and SPORTIF V compared ximelagatran with warfarin. There was no difference between the rate of stroke, thrombo-embolic event and major bleeding. Ximelagatran was associated with less combined major and minor bleeding, and with an increase in serum transaminases. w22,w23
Idraparinuxw27
Subcutaneous
Weekly injections
A heparin derivative which selectively inhibits Factor Xa
Fast
3-6 hours
None
No
AMADEUS trial is currently comparing idraparinux with warfarin in the prevention of thrombo-embolic events in patients with atrial fibrillation. w24
Note: Ximelagatran and Idraparinux are not yet licensed for use in AF
Table C (Posted as supplied by the authors)
Novel anti-arrhythmic drugs and their potential use in atrial fibrillation.
Drug
Mechanism of action
Route of administration
Use in atrial fibrillation
Comments
Pilisicainidew28
Pure Na-channel blocker
(a new class I drug)
Oral
Cardioversion
Maintenance of sinus rhythm
● Unlike other class I drugs, not negatively inotropic.
● Safe in heart failure patients and post-cardiac surgery.
● Further studies required.
Dofetilide w29,w30
K-channel blocker
(a new class III drugs)
Oral
Intravenous
Cardioversion
Maintenance of sinus rhythm
● Licensed in US for persistent atrial fibrillation.
● Effective in maintenance of sinus rhythm post-cardioversion.
● Risk of torsade de pointes.
● Safe in patients with heart failure.
Ibutilide w31,w32
K-channel blocker
(a new class III drug)
Intravenous
Cardioversion
● Licensed in US for cardioversion of recent-onset atrial fibrillation.
● Risk of torsade de pointes.
● Safe in patients with heart failure.
Azimilide w33,w34
K-, Na- and Ca- channel blocker
(a new class III drug)
Oral
Cardioversion
Maintenance of sinus rhythm
● Unlike dofetilide, no "reverse-use dependence" phenomenon.
● Excellent tolerability and oral absorption.
● Safe in patients with heart failure.
● Undergoing phase III trials.
Tedisamil w35,w36
K-channel blocker
(a new class III drug)
Intravenous
Cardioversion
Maintenance of sinus rhythm
● Initially developed as an anti-anginal agent.
● Potential for use in patients with co-existing ischaemic heart disease.
● Recently completed phase II trials.
● Can cause hypertension. Therefore further evaluation required.
Dronedarone w37
An amiodarone derivative, but without the iodine component
Oral
Cardioversion
Maintenance of sinus rhythm
Rate control
● No thyroid, ocular or pulmonary toxicity as seen with amiodarone.
● Has the therapeutic potential to replace amiodarone.
● Recently completed phase II trials.
Amio-aqueous w38
An aqueous formulation of intravenous amiodarone
Intravenous
Cardioversion
● Aqueous form lacks the vasoactive solvents of amiodarone.
● Therefore, not associated with hypotension, as seen with standard intravenous amiodarone.
● Undergoing phase III trials.
RSD-1235 w39
A selective atrial K- and Ca-channel blocker
Oral
Intravenous
Cardioversion
Maintenance of sinus rhythm
● Due to atrial selectivity, potentially less negatively inotropic and lower risk of ventricular arrhythmias.
● Completed phase II trials.
Piboserod w40
Atrial 5HT4-receptor blocker
Oral
Cardioversion
Maintenance of sinus rhythm
● Based on concept that 5-HT (serotonin) can induce supraventricular arrhythmias by interacting with 5HT4-receptors.
● Currently undergoing phase III trials.
CVT-2759 w41,w42
CVT-510
SHA-040
Partial adenosine (A1) agonists at the AV node.
Oral
Intravenous
Rate control
● A1 –receptors are concentrated around the AV node.
● No bronchoconstriction and hypotension (mediated by A2 –receptors)
● Studies in humans awaited.
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