Novel anticoagulants ‘superior’ to warfarin in patients with AF
MedWire News: Novel oral anticoagulants (NOACs) such as dabigataran, rivaroxaban, and apixaban provide a superior outcome to warfarin when given to patients with nonvalvular atrial fibrilliation (AF), Italian research shows.
NOACs significantly reduced the risk for stroke or systematic embolism without increasing the risk for major bleeding, report Davide Capodanno and colleagues from the University of Catania.
"Warfarin, despite its known limitations, is the reference standard treatment for patients with AF and risk factors for stroke," the researchers remark.
In recent years, there has been a renewed interest towards the clinical development of NOACs, which act by directly inhibiting key coagulation factors such as activated thrombin (dabigatran) or factor X (rivaroxaban, apixaban, edoxaban, and betrixaban), that do not require international normalized ratio monitoring, and have the potential to be more patient-friendly for chronic use.
Evidence for the efficacy of some of these drugs is rapidly accumulating from large phase III trials, but none of the individual studies were powered to detect a difference in mortality or stroke compared with warfarin.
To address this, Capodanno and team performed a meta-analysis of phase III trials that compared NOACs with warfarin to determine whether they improve the clinical outcomes of patients with non-valvular AF.
They identified three randomized trials (RE-LY, ROCKET-AF, and ARISTOTLE) that met their inclusion criteria by comparing NOACs (dabigataran, rivaroxaban, and apixaban) with warfarin in patients with non-valvular AF.
The primary efficacy endpoint was the incidence of stroke or systemic embolism, while the primary safety endpoint was the incidence of major bleeding.
Of 50,578 randomized patients included in the three studies, 28,342 were assigned to NOACs and 22,236 were assigned to warfarin.
As reported in the International Journal of Cardiology, NOACs were associated with a significant 18% relative reduction in the composite of stroke or systemic embolism compared with warfarin (2.8 vs 3.5%), with a 12% reduction in death (6.0 vs 6.3%), and a 21% reduction in stroke alone (2.4 vs 3.0%).
The reduction in stroke was mainly driven by significantly fewer hemorrhagic strokes (0.3 vs 0.8%, odds ratio=0.79), the researchers note.
There was no significant difference between NOACs and warfarin in the rate of major bleeding, at 5.0% versus 5.6%, but NOACs were associated with significantly lower rates of intracranial bleeding (0.6 vs 1.3%) and significantly higher rates of gastrointestinal bleeding (2.3 vs 1.3%) compared with wafarin.
"Based on these results, NOACs approved from regulatory agencies should be used as first-line agents for antithrombotic management of patients with non-valvular AF," Capodanno and co-authors conclude.
They caution, however, that NOACs are not currently recommended in AF patients with other reasons for warfarin therapy, such as those with prosthetic heart valves.
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By Laura Cowen