The AHA Guidelines and Scientifi c Statements Handbook
Thrombin Inhibitor Ximelagatran), revealed a 6.0%
incidence of liver transaminase abnormality above
three times normal values and 1–2 deaths from liver
disease. The primary end-point of all strokes (isch-
emic or hemorrhagic) and systemic embolism was
reached in 1.6% of patients on ximelagatran and
1.2% of patients on warfarin. Although promising,
the FDA denied approval in 2004. Despite the failure
of ximelagatran, there are several promising drugs
in the mid to late phases of development. Dabiga-
tran etexilate, another oral direct thrombin inhibi-
tor, is examined in the phase III RELY trial
(Randomized Evaluation of Long Term Anticoagu-
lant Therapy), comparing two different fi xed doses
versus dose-adjusted warfarin. RELY is expected to
be completed in 2009.
Factor Xa is another therapeutic target for inhibi-
tion that has large bodies of evidence supporting its
effi cacy for treatment and prevention of thrombo-
embolism. Until recently, factor Xa inhibitors
required injection, but several oral compounds are
presently undergoing phase II and III investigation.
A phase III trial of Rivaroxaban comparing its effi -
cacy to dose adjusted warfarin for the prevention of
stroke in atrial fi brillation is enrolling patients.
Another, apixaban, is in a similar stage of develop-
ment. It is likely that some of these compounds will
provide viable alternatives to warfarin for patients at
moderate to high risk for stroke while low risk
patients still will be well served by aspirin.
Ablation strategies
Many trials involving ablation strategies for atrial
fi brillation are under way, and an important phar-
macological trial on dronedarone has just been
published [28]. They are expected to help answer
which ablation techniques that are to be preferred
in maintaining sinus rhythm. The trials compare
complete versus incomplete electrical isolation of
the pulmonary veins (German Atrial Fibrillation
Network) and trigger-based ablation techniques
(pulmonary vein isolation) versus substrate-based
ablation techniques guided by high-frequency, frac-
tionated electrograms (University of Toronto).
MANTRA-PF (Medical Antiarrhythmic Treatment
or Radiofrequency Ablation in Paroxysmal Atrial
Fibrillation) and RAAFT (First Line Radiofrequency
Ablation Versus Antiarrhythmic Drugs for Atrial
Fibrillation Treatment) are both prospective, ran-
domized, multi-center studies comparing pharma-
cologic anti-arrhythmic therapy to pulmonary vein
isolation. Expected enrollment is 300 and 400
patients respectively with expected completion of
2009 or later. CAPTAF (Catheter Ablation com-
pared with Pharmacological Therapy for Atrial
Fibrillation) has as its primary objective to deter-
mine if the effects of the strategy catheter ablation
of AF is superior to optimized conventional phar-
macological therapy on Quality of Life in patients
with symptomatic AF.References available online at http://www.Wiley.com/go/
AHAGuidelineHandbook.During the production of this book this relevant
AHA statement and guideline was published: ACC/
AHA/Physician Consortium 2008 Clinical Perfor-
mance Measures for Adults With Nonvalvular Atrial
Fibrillation or Atrial Flutter, http://circ.ahajournals.
org/cgi/content/full/117/8/1101.