Major bleeding less in NOACs compared to warfarin
Non-vitamin K oral anticoagulants (NOACs) are as effective as warfarin in preventing stroke for atrial fibrillation patients, but cause less major bleedings, a new retrospective register study shows.
“[W]e found that NOACs were not superior to warfarin, neither for preventing stroke or systemic embolism, nor for death, stroke or myocardial infarction,” researchers said.
“Our main finding is that the risk of serious bleeding, particularly intracranial bleeding, is lower with NOACs than with warfarin, despite the warfarin treatment being well-managed by international standards,” they added.
The annual rate of overall major bleeding was significantly lower in the NOAC (2.76 percent; n=283) than in the matched warfarin (3.61 percent; n=350) group. The risk of major bleeding was also significantly lower in the NOAC (hazard ratio [HR], 0.78; 0.67 to 0.92; p=0.003) than in the warfarin group. [PLoS One 2017;doi:10.1371/journal.pone.0181000]
Specifically, the NOAC group had significantly lower annual rates of intracranial bleeding (0.40 vs 0.69 percent) and other bleeding events (1.45 vs 2.08 percent) than the warfarin group. The corresponding risks were also significantly lower (HR, 0.59; 0.40 to 0.87; p=0.008 and HR, 0.71; 0.57 to 0.89; p=0.003).
The resulting rate in intracranial bleeding reflects rates in pivotal NOAC studies, which peg the annual rates at 0.70 to 0.85 percent, the authors said. On the other hand, a 0.69 percent annual rate is “markedly higher than the 0.44 percent previously found in Swedish patients with atrial fibrillation.” [JAMA Cardiol 2016; 1:172-180]
“Relatively short treatment duration and the fact that we sought for intracranial bleedings not only in the National Patient Register but also in the Cause of Death register, as well as in Riksstroke could at least partly explain the higher bleeding rate found in the present study,” they explained.
There was no significant difference in the annual rates (1.26 vs 1.14 percent) and risk (HR, 1.14; 0.88 to 1.46; p=0.32) of gastrointestinal bleeding between the two groups.
On the other hand, the annual rate (1.35 vs 1.58 percent) and risk (HR, 0.89; 0.69 to 1.15; p=0.36) for all-cause stroke and systemic embolism were comparable between patients who took NOACs and those who took warfarin.
There were also no significant differences in the annual rate (1.04 vs 1.03 percent) and risk (HR, 1.04; 0.75 to 1.43; p=0.830) of ischaemic stroke, while haemorrhagic stroke had significantly lower rates (0.16 vs 0.35 percent) and risks (HR, 0.49; 0.28 to 0.86; p=0.01) in the NOAC than in the warfarin group.
Matched warfarin was not superior to NOACs in terms of annual rates and risks of all-cause mortality (4.66 vs 4.21 percent; HR, 0.94; 0.82 to 1.07; p=0.33) and myocardial infarction (1.45 vs 1.25 percent; HR, 0.95; 0.72 to 1.24; p=0.68).
The study included 49,011 atrial fibrillation patients; 12,694 (mean age 72.2 years; 58.2 percent male) were starting NOAC treatment while a propensity score-matched 36,317 (mean age 72.3 years; 57.1 percent male) were starting warfarin. Of the NOAC group, 40.3 received dabigatran, 31.2 percent rivaroxaban, 28.5 percent apixaban.
“The lack of difference in efficacy outcomes could be due to low numbers of events, but the rates of haemorrhagic complications resemble the findings in the randomised trials. The overall efficacy and safety of NOACs compared to warfarin seem to be confirmed in our study,” said investigators.