title: Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation: a look beyond the excellent results.
abstract: In this overview we address the three phase III studies that compared new oral anticoagulants (dabigatran, rivaroxaban and apixaban) with warfarin in the setting of stroke prevention in atrial fibrillation. Strengths and weaknesses of the studies were examined in detail through indirect comparison. We analyze and comment the inclusion and exclusion criteria, the characteristics of randomized patients, the primary efficacy and safety end points and side effects. All new oral anticoagulants resulted in being non-inferior to vitamin K antagonists in reducing stroke or systemic embolism in patients with atrial fibrillation. Dabigatran 150 mg and apixaban were superior to vitamin K antagonists. Importantly, new oral anticoagulants significantly reduced hemorrhagic stroke in all three studies. Major differences among new oral anticoagulants include the way they are eliminated and side effects. Both dabigatran and apixaban were tested in low- to moderate-risk patients (mean CHADS2 [Congestive heart failure, Hypertension, Age, Diabetes, Stroke] score = 2.1-2.2) whereas rivaroxaban was tested in high-risk patients (mean CHADS2 score = 3.48) and at variance with dabigatran and apixaban was administered once daily. Apixaban significantly reduced mortality from any cause. The choice of a new oral anticoagulant should take into account these and other differences between the new drugs.
authors: Department of Clinical Cardiology, Thrombosis Centre, University of Padua, Padua, Italy. vittorio.pengo@unipd.it
authors: V
authors: V
authors: Pengo
authors: L
authors: L
authors: Crippa
authors: A
authors: A
authors: Falanga
authors: G
authors: G
authors: Finazzi
authors: F
authors: F
authors: Marongiu
authors: M
authors: M
authors: Moia
authors: G
authors: G
authors: Palareti
authors: D
authors: D
authors: Poli
authors: S
authors: S
authors: Testa
authors: E
authors: E
authors: Tiraferri
authors: A
authors: A
authors: Tosetto
authors: A
authors: A
authors: Tripodi
authors: S
authors: S
authors: Siragusa
authors: C
authors: C
authors: Manotti
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D019317:Evidence-Based Medicine; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage; D061214:Patient Safety; D011314:Preventive Health Services; D011720:Pyrazoles / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage; D015091:beta-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran