Trends of use and factors that determine the choice of oral anticoagulants in women and men with atrial fibrillation.

The aim was to identify sex-specific factors linked with oral anticoagulant initiation in a cohort of patients with atrial fibrillation using administrative data from Quebec (Canada) between 2014 and 2017. Cohort entry defined as new users, that is, no claims in last 12 months, a cohort of 32 050 patients was stratified in two groups, that is, women and men. Multivariable regression models were used to identify factors of initiations for low- and standard-dose direct oral anticoagulants (DOACs) versus warfarin, and low- versus standard-dose DOACs. In both sexes, warfarin initiation decreased and DOAC initiation increased, with year of initiation as major factors of DOACs use. In 2017, the increase was of 2- to 4-fold and 3- to 8-fold for low- and standard-dose DOACs (vs. warfarin), respectively. The proportion of patients starting on a low-dose DOAC was higher in women than men. Older age for both sexes and CHADS2 score ≥2 (only women) were major factors of low-dose dabigatran and rivaroxaban versus warfarin use. The only significant factor of standard-dose DOAC versus warfarin use was age of 65-79 for women or men treated with apixaban by 1.8- and 1.4-fold, respectively. Factors that made women and men less likely to receive a standard-dose DOAC versus warfarin were higher CHADS2 (for dabigatran and rivaroxaban), HAS-BLED and frailty scores, prior coronary disease, major bleeding, and chronic kidney disease (CKD) status. The choice of a low- versus standard-dose DOAC was mainly driven by age and CKD, and higher CHADS2 score (for dabigatran and apixaban) for both sexes.

Polypharmacy and risk of mortality among patients with heart failure following hospitalization: a nested case-control study.

Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administrative databases, Canada from 1999 to 2015. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥ 10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs within three months prior to the case or the control selection date. We conducted a nested case-control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression during one-year of follow-up. We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (RR 0.97, 95%CI 0.82-1.15) nor non-CV polypharmacy (RR 0.93, 95%CI 0.77-1.12) were associated with lower mortality risk. However, all polypharmacy (RR 1.31, 95%CI 1.07-1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high Frailty score, hydralazine and spironolactone users were associated with increasing mortality risk, ranging from 15 to 61%, while use of angiotensin II inhibitors, beta-blockers, statins, anticoagulant, and antiplatelets were associated with lower risk, ranging from 23 to 32%.

Predicting major bleeding among hospitalized patients using oral anticoagulants for atrial fibrillation after discharge.

AIM: Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF. METHODS: We identified patients hospitalized for any cause and discharged alive in the community from 2011 to 2017 with a primary or secondary diagnosis of AF in Quebec's RAMQ and Med-Echo administrative databases. Cohort entry occurred at the first OAC claim. Patients were categorized according to OAC type. Outcomes were incident MB, gastrointestinal bleeding (GIB), non-GI extracranial bleeding (NGIB) and intracranial bleeding within 1 year of follow-up. Covariates included age, sex, co-morbidities (within 3 years before cohort entry) and medication use (within 2 weeks before cohort entry). We used logistic-LASSO and adaptive logistic-LASSO regressions to identify MB predictors among OAC users. Discrimination and calibration were assessed for each model and a global model was selected. Subgroup analyses were performed for MB subtypes and OAC types. RESULTS: Our cohort consisted of 14,741 warfarin, 3,722 dabigatran, 6,722 rivaroxaban and 11,196 apixaban users aged 70-86 years old. The important MB predictors were age, prior MB and liver disease with ORs ranging from 1.37-1.64. The final model had a c-statistic of 0.63 (95% CI 0.60-0.65) with adequate calibration. The GIB and NGIB models had similar c-statistics of 0.65 (95% CI 0.63-0.66) and 0.67 (95% CI 0.64-0.70), respectively. CONCLUSIONS: MB and MB subtype predictors were similar among DOAC and warfarin users. The predictors selected by our models and their discriminative potential are concordant with published data. Thus, these models can be useful tools for future pharmacoepidemiologic studies involving older oral anticoagulant users with AF.