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Assessing Safety of Direct Thrombin Inhibitors, Direct Factor Xa Inhibitors and Vitamin K Antagonists in Patients
Marie Linder1, Anastasia Iliadou Nyman2,3, Helle Kieler1
1Centre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm, Sweden.
Insights
First-time elderly users of direct oral anticoagulants (DOACs) showed increased gastrointestinal bleeding risk compared to vitamin K antagonists. Further studies are needed to investigate the observed excess mortality risk in these patients.
Area of Science:
- Cardiology
- Pharmacology
- Geriatrics
Background:
- Atrial fibrillation (AF) is a common condition in the elderly, increasing stroke risk.
- Anticoagulant therapy, including vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs), is crucial for stroke prevention in AF patients.
- Real-world data on the comparative safety of first-time anticoagulant use in elderly populations are essential.
Purpose of the Study:
- To assess the association between initiating direct oral anticoagulants (dabigatran, apixaban, rivaroxaban) versus vitamin K antagonists (warfarin) and the risk of bleeding or mortality in elderly patients with atrial fibrillation.
- To compare direct thrombin inhibitors (DTIs) and direct factor Xa inhibitors (FXaIs) against VKAs and against each other in a real-world Swedish setting.
Main Methods:
- A nationwide, register-based cohort study in Sweden (2012-2016) included first-time anticoagulant users aged over 60 with newly diagnosed atrial fibrillation.
- Propensity score matching was used to compare three groups: DTIs, FXaIs, and VKAs.
- Outcomes included gastrointestinal, any, and intracranial bleeding, and all-cause mortality, analyzed using Cox proportional hazard models adjusted for CHA2DS2VASc and HAS-BLED scores.
Main Results:
- The study included 26,436 patients across three comparison groups.
- Numerically high, though imprecise, hazard ratios for gastrointestinal bleeding were observed in elderly women using DTIs versus VKAs.
- Increased risks for any bleeding were noted in both sexes aged 80-85 and above 85 years when comparing DTIs to VKAs.
- Excess mortality was observed across age groups for both naive and experienced anticoagulant users.
Conclusions:
- First-time use of DTIs or FXaIs in elderly AF patients is associated with an increased gastrointestinal bleeding risk, aligning with prior research.
- The potential for excess mortality associated with these anticoagulants warrants further investigation.
Purpose:
To evaluate associations between first-time use of direct oral anticoagulants or vitamin K antagonists and bleeding risk or mortality in the elderly with atrial fibrillation in a real-world setting in Sweden.
Patients And Methods:
The study population comprises first-time users, above age 60, of dabigatran, apixaban, rivaroxaban, or warfarin, with first atrial fibrillation occurrence within 6 months before dispensing (2012-2016). Outcomes were gastrointestinal, any, or intracranial bleeding, and mortality. Exposure started at first dispensing of a study drug. Follow-up continued until outcome, end of drug supply, dispensing of another study drug, death or end of study (December 2016). We conducted a propensity score matched, nationwide register-based cohort study including three treatment groups: direct thrombin inhibitors, direct factor Xa inhibitors and vitamin K antagonists, each compared to the other two, focusing on subgroups of age and sex. Cox proportional hazard models adjusted for CHA2DS2VASc and HAS-BLED scores provided hazard ratios with 95% confidence intervals.
Results:
The matched study populations consisted of 7,264 patients for the direct thrombin inhibitors vs vitamin K antagonists comparison, 12,566 patients for the direct factor Xa inhibitors vs vitamin K antagonists comparison and 6,606 patients for the direct factor Xa inhibitors vs direct thrombin inhibitors comparison, in total 26,436 patients. Numerically high, but imprecise, hazard ratios for gastrointestinal bleeding were observed for women aged 75-80, 80-85, or above 85 years, eg 6.00 (1.02, 113.47) for direct thrombin inhibitors vs vitamin K antagonists. For both sexes, numerically high hazard ratios for any bleeding were observed in ages 80-85, or above 85 years, eg 2.90 (1.01, 10.41) for direct thrombin inhibitors vs vitamin K antagonists. Numerically high HRs for intracranial bleeding were observed for women aged 75-80 or 80-85 years, eg 2.70 (0.65, 18.19) for direct factor Xa inhibitors vs vitamin K antagonists. Excess mortality was observed in both sexes, across age groups, for naive and experienced anticoagulant users.
Conclusion:
The observed increased gastrointestinal bleeding risk in first-time users of direct thrombin inhibitors or direct factor Xa inhibitors is consistent with previous studies. The possible risk of excess mortality merits further studies.
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