The risk of severe uterine bleeding (SUB) reported in oral anticoagulant (OA) clinical trials is likely underestimated because of the low representation of women of reproductive age. In a previous letter, we reported the SUB incidence in women who received OA treatment using real-world data. In this study, we examined the incidence of SUB among women presenting with uterine bleeding (UB) with and without ongoing OA (warfarin or non-vitamin K oral anticoagulants) exposure to contextualize our previous findings.
Using the US Food and Drug Administration’s Sentinel System, we summarized the incidences as proportions of women receiving same-day transfusion (SUB-T) or receiving gynecologic surgeries within 30 days (SUB-S). This was done for all eligible women who had a first UB diagnosis (index date) between October 19, 2010 and September 30, 2015, preceded by no such diagnosis but continuous medical and prescription drug coverage in the recent 6 months. The Sentinel System encompasses administrative data, health insurance claims, and electronic health records, which are routinely collected from inpatient, outpatient, and institutional care settings by 16 national and regional data partners. We differentiated OA users and nonusers by the presence of the following: (1) OA exposure (evidenced by the lasting days supply of outpatient pharmacy dispensing) on the index date and (2) diagnosis of atrial fibrillation/flutter or venous thromboembolism in the 183 days before or on the index date (baseline period). Women who experienced joint replacement at the baseline were excluded.
We identified 80,967 OA users and 4,245,694 nonusers. OA nonusers were younger (mean age 44.1 vs 69.3 years) at the time of their UB diagnosis and more likely utilized intrauterine device (IUD) (1.7% vs 0.7%) or oral contraception (14.6% vs 2.2%) at baseline ( Table ). Overall, the SUB-T incidence was higher in OA users than nonusers (2.6% vs 0.4%), but the SUB-S incidence was comparable (7.3% vs 7.2%). When stratified by age, the OA users consistently had higher SUB-T and SUB-S incidences than nonusers during the reproductive ages ( Figure ). In fact, the differences in the SUB-T incidences were significant across all the age groups (standardized differences <−0.1). Within the age group of 18–50 years, prior exposures to IUD and oral contraception were both associated with a lower SUB incidence (SUB-T: IUD or oral contraception use 0.1% vs no use 0.4%; SUB-S: IUD 4.0% vs 7.0%, oral contraception 4.7% vs 7.4%) for OA nonusers; however, these trends attenuated among the OA users. In contrast, having a history of gynecologic disorders was associated with higher SUB incidence regardless of OA use in the same age group. Significantly, higher SUB-T incidences in OA users persisted across all assessed strata.
|Characteristics||No OA use (n=4,245,694)||Ongoing OA use (n=80,967)|
|Age in y, mean (SD)||44.1||(14.5)||69.3||(15.3)|
|Ongoing OA use|
|Comorbidity and health services utilization in the past 6 mo, including the day of uterine bleeding|
|Combined comorbidity score, b mean (SD)||0.4||(1.2)||3.3||(3.0)|
|Atrial fibrillation or atrial flutter||—||65.7|
|Deep vein thrombosis or pulmonary embolism||—||46.9|
|Gynecologic disorder c||15.2||14.4|
|Intrauterine device use||1.7||0.7|
|Ambulatory encounters, mean (SD)||7.8||(9.2)||20.4||(16.8)|
|Emergency room encounters, mean (SD)||0.3||(1.0)||0.9||(1.9)|
|Inpatient hospital encounters, mean (SD)||0.1||(0.4)||0.6||(1.1)|
|Other ambulatory encounters, d mean (SD)||2.0||(4.7)||11.7||(17.9)|
|Drug utilization by class, mean (SD)||4.3||(3.7)||11.2||(5.2)|
|Drug utilization by filled prescription, mean (SD)||10.8||(12.9)||37.0||(26.3)|