A major observational study comparing DOACS in older patients with atrial fibrillation has shown they all have significant benefits over warfarin in terms of reducing thromboembolic stroke, intracranial haemorrhage and all-cause mortality.
Twice-daily DOACS dabigatran and apixaban were associated with a more favourable benefit-to-harm ration than the once-daily rivaroxaban, according to the retrospective new-user cohort study conducted by US Food and Drug Administration (FDA) staff.
The study compared outcomes for Medicare enrolled patients over the age of 65 with non-valvular AF who started either warfarin (183,318), dabigatran (150mg twice daily, n = 86,198), apixaban (5mg twice daily n = 73,039) or rivaroxaban (20mg once daily, n = 106,389).
Based on propensity score-adjusted hazard ratios, the study found that the DOACs were associated with a statistically significant 20-29% reduced risk of thromboembolic stroke and 35-62% reduced risk of intracranial haemorrhage compared to warfarin. Use of DOACs was also associated with a significant 19-34% reduction in all-cause mortality compared to warfarin.
When compared to warfarin, the risk of major gastrointestinal bleeding was increased with dabigatran [HR 1.16] and rivaroxaban [1.48] and decreased with apixaban (HR 0.52].
When compared with each other, the DOACS were similar in terms of thromboembolic stroke but rivaroxaban was associated with a significantly increased risk of intracranial haemorrhage vs dabigatran (HR 1.71) and major extracranial bleeding vs dabigatran (HR 1.32) and apixaban (HR 2.70). It was also associated with increased risk of death (vs dabigatran HR 1.12, vs apixaban HR 1.23).
The study authors, led by David Graham of the FDA’s Centre for Drug Evaluation and Research (CDER) said the more favourable benefit-to-harm balance seen with dabigatran and apixaban over rivaroxaban may be related to the twice- versus once-daily dosages, since they each had a half lives of about 12 hours.
Writing in the American Journal of Medicine, they said the findings were important because there had been no head-to-head randomised controlled trials of DOACs and the observational studies comparing their effects had been small and rarely examined thromboembolic stroke.
Professor Andrew Sindone, director of the heart failure unit and the department of cardiac rehabilitation at Concord Hospital in Sydney said the US findings provided confirmation from real world data of the efficacy and safety of DOACs.
“I think the bottom line is that we can say this data reinforces our impression from clinical trials that all DOACS are very safe and they increase survival and reduce stroke and intracranial bleeding compared to warfarin,” he said.
He said the “subtle” differences between DOACs should be interpreted in light of the drugs all being used at their highest doses in the US study, whereas they might be used in lower doses in some patients in Australia.
Professor Sindone declared an interest in acting as a consultant to the sponsors of all three DOACS available in Australia.