Dataset Information

Equivalent inpatient mortality among direct-acting oral anticoagulant and warfarin users presenting with major hemorrhage.

ABSTRACT:

Background

Extrapolation of clinical trial results comparing warfarin and direct-acting oral anticoagulant (DOAC) users experiencing major hemorrhage to clinical care is challenging due to differences seen among non-randomized oral anticoagulant users, bleed location, and etiology. We hypothesized that inpatient all-cause-mortality among patients presenting with major hemorrhage differed based on the home-administered anticoagulant medication class, DOAC versus warfarin.

Methods

More than 1.5 million hospitalizations were screened and 3731 patients with major hemorrhage were identified in the REDS-III Recipient Database. Propensity score matching and stratification were used to account for potentially confounding factors.

Results

Inpatient all-cause-mortality was lower for DOAC (HR = 0.60, 95%CI 0.45-0.80, p = 0.0005) before accounting for confounding and competing events. Inpatient all-cause-mortality for 1266 propensity-score-matched patients compared using proportional hazards regression did not differ (HR = 0.84, 95%CI 0.58-1.22, p = 0.36). Inpatient all-cause-mortality in stratified analyses (warfarin as reference) produced: HR = 0.69 (95%CI 0.31-1.55) for traumatic head injuries; HR = 1.10 (95%CI 0.62-1.95) for non-traumatic head injuries; HR = 0.62 (95%CI 0.20-1.94) for traumatic, non-head injuries; and HR = 0.69 (95%CI 0.29-1.63) for non-traumatic, non-head injuries. Mean time to discharge was shorter for DOAC (HR = 1.17, 95%CI 1.05-1.30, p = 0.0034) in the propensity score matched analysis. Plasma transfusion occurred in 42% of warfarin hospitalizations and 11% of DOAC hospitalizations. Vitamin K was administered in 63% of warfarin hospitalizations.

Conclusions

After accounting for differences in patient characteristics, location of bleed, and traumatic injury, inpatient survival was no different in patients presenting with major hemorrhage while on DOAC or warfarin.

SUBMITTER: Bialkowski W

PROVIDER: S-EPMC7035631 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Equivalent inpatient mortality among direct-acting oral anticoagulant and warfarin users presenting with major hemorrhage.

Bialkowski Walter W Tan Sylvia S Mast Alan E AE Kiss Joseph E JE Kor Daryl D Gottschall Jerome J Wu Yanyun Y Roubinian Nareg N Triulzi Darrell D Kleinman Steve S Choi Young Y Brambilla Donald D Zimrin Ann A

Thrombosis research 20191125

<h4>Background</h4>Extrapolation of clinical trial results comparing warfarin and direct-acting oral anticoagulant (DOAC) users experiencing major hemorrhage to clinical care is challenging due to differences seen among non-randomized oral anticoagulant users, bleed location, and etiology. We hypothesized that inpatient all-cause-mortality among patients presenting with major hemorrhage differed based on the home-administered anticoagulant medication class, DOAC versus warfarin.<h4>Methods</h4>M ...[more]

PMID: 31794885

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Project description:Background Reduced time in international normalized ratio therapeutic range (TTR) limits warfarin safety and effectiveness. In patients switched from warfarin to direct oral anticoagulants (DOACs), patient factors associated with low TTR could also increase risk of DOAC nonadherence. We investigated the relationship between warfarin TTR and DOAC adherence in warfarin-treated patients with atrial fibrillation switched to DOAC. Methods and Results Using data from the Veterans Health Administration, we identified patients with atrial fibrillation switched from warfarin to DOAC (switchers) or treated with warfarin alone (non-switchers). Logistic regression was used to evaluate association between warfarin TTR and DOAC adherence. We analyzed 128 605 patients (age, 71±9; 1.6% women; CHA2DS2-VASc 3.5±1.6); 32 377 switchers and 96 228 non-switchers. In 8016 switchers with international normalized ratio data to calculate 180-day TTR before switch, TTR was low (median 0.45; IQR, 0.26-0.64). Patients with TTR <0.5 were more likely to be switched to DOAC (odds ratio [OR],1.68 [95% CI,1.62-1.74], P<0.0001), as were those with TTR <0.6 or TTR <0.7. Proportion of days covered ≥0.8 was achieved by 76% of switchers at 365 days. In low-TTR individuals, proportion of days covered ≥0.8 was achieved by 70%, 72%, and 73% of switchers with TTR <0.5, 0.6, and 0.7, respectively. After multivariable adjustment, TTR <0.5 decreased odds of achieving 365-day proportion of days covered ≥0.8 (OR, 0.49; 0.43-0.57, P<0.0001), with similar relationships for TTR <0.6 and TTR <0.7. In non-switchers with TTR <0.5, long-term TTR remained low. Conclusions In patients with atrial fibrillation switched from warfarin to DOAC, most achieved adequate DOAC adherence despite low pre-switch TTRs. However, TTR trajectories remained low in non-switchers. Patients with low warfarin TTR more consistently achieved treatment targets after switching to DOACs, although adherence-oriented interventions may be beneficial.

Project description:ObjectiveThe p.V433M in cytochrome P450 4F2 (rs2108622, CYP4F2*3) is associated with a higher warfarin dose and lower risk of hemorrhage among European Americans. We evaluate the influence of CYP4F2*3 on warfarin dose, time to target international normalized ratio (INR), and stable dose, proportion of time spent in target range (PTTR), as well as the risk of overanticoagulation and hemorrhage among European and African Americans.DesignCYP4F2*3 was genotyped in 1238 patients initiated on warfarin in a prospective inception cohort. Multivariable linear regression was used to assess warfarin dose and PTTR; proportional hazards analysis was performed to evaluate time to target INR and stable dose, overanticoagulation, and hemorrhage.SettingTwo outpatient anticoagulation clinics.ParticipantsA total of 1238 anticoagulated patients.OutcomesWarfarin dose (mg/day), time to target INR and stable dose, PTTR, overanticoagulation (INR more than 4), and major hemorrhage.ResultsMinor allele frequency for the CYP4F2*3 variant was 30.3% among European Americans and 8.4% among African Americans. CYP4F2*3 was associated with higher dose among European Americans but not African Americans. Compared to CYP4F2*1/*1, *1/*3 was associated with a statistically nonsignificant increase in dose (4.5%, p=0.22) and *3/*3 was associated with a statistically significant increase in dose (13.2%, p=0.02). CYP4F2 genotype did not influence time to target INR, time to stable dose, or PTTR in either race group. CYP4F2*3/*3 was associated with a 31% lower risk of over anticoagulation (p=0.06). Incidence of hemorrhage was lower among participants with CYP4F2 *3/*3 compared with *1/*3 or *1/*1 (incidence rate ratio = 0.45, 95% confidence interval 0.14-1.11, p=0.09). After controlling for covariates, CYP4F2 *3/*3 was associated with a 52% lower risk of hemorrhage, although this was not statistically significant (p=0.24).ConclusionPossession of CYP4F2*3 variant influences warfarin dose among European Americans but not African Americans. The CYP4F2-dose, CYP4F2-overanticoagulation, and CYP4F2-hemorrhage association follows a recessive pattern with possession of CYP4F2*3/*3 genotype likely demonstrating a protective effect. These findings need further confirmation.

Project description:ImportanceDirect oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data sourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study selectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data extraction and synthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main outcomes and measuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and relevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Dataset Information

Equivalent inpatient mortality among direct-acting oral anticoagulant and warfarin users presenting with major hemorrhage.

Background

Methods

Results

Conclusions

Publications

Equivalent inpatient mortality among direct-acting oral anticoagulant and warfarin users presenting with major hemorrhage.

Similar Datasets

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