Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban

Duration of menopausal vasomotor symptoms over the menopause transition

IMPORTANCE: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES: To determine total duration of frequent VMS ( \u3e /= 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS: The Study of Women\u27s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, \u3e 11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women

Characterizing the trajectories of vasomotor symptoms across the menopausal transition

OBJECTIVE: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women. METHODS: The Study of Women\u27s Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling. RESULTS: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory. CONCLUSIONS: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS

Abstract P189: Associations between Lactation and Maternal Measures of Total and Regional Adiposity 15 Years Postpartum: Results from the Study of Women’s Health Across the Nation

Objective: It has been reported that mothers who do not breastfeed are at an increased risk of T2DM, metabolic syndrome, and CVD. We hypothesize that lactation may influence cardio-metabolic risk by altering maternal body composition. We examined the extent to which lactation was associated with regional and total adiposity in a sample of US women 15 years after their last birth. Study Design : Cross-sectional analysis of data provided by 1,268 women aged 45-58 who enrolled in the Study of Women’s Health Across the Nation (1996 -1997). Adiposity was assessed using dual-energy X-ray absorptiometry. History of lactation was self-reported and categorized into three groups: mothers who breastfed for ≥3 months after every birth, those who discontinued lactation within 3 months of some births, and those who never breastfed. Results: Compared with mothers who breastfed after every birth for at least 3 months, mothers who never breastfed had 0.87 kg greater trunk fat mass (FM), 1.3% greater % trunk FM, 1.3% lower % leg FM, and 0.075 greater trunk to leg FM ratio after adjustment for age, parity, height, years since last birth, race/ethnicity, socioeconomic, lifestyle, psychological, and family history variables, maximum gestational weight gain, and menopausal status. After additional adjustment for current BMI, women who never breastfed had 0.40 kg greater trunk FM and 0.053 greater trunk to leg FM ratio than mothers who breastfed every child for ≥3 months. Similarly, mothers who discontinued lactation within 3 months of some births had 0.28 kg greater trunk FM and 0.87% lower % leg FM than mothers who consistently breastfed. Conclusion : Women who did not breastfeed for at least 3 months after every birth exhibit less favorable body fat distributions 15 years postpartum. These results provide a potential physiologic basis for prior findings that women who do not breastfeed their children face increased risk of diabetes, the metabolic syndrome, and cardiovascular disease. Given existing disparities in rates of lactation, obesity and CVD, these findings have great clinical relevance and suggest the need for targeted lactation support for women at risk of cardiovascular disease

Change in sexual functioning over the menopausal transition

ObjectiveThe aim of the study was to identify whether there is a decline in sexual functioning related to the menopausal transition or to hysterectomy.MethodsIn a cohort of 1,390 women aged 42 to 52, with intact uterus and at least one ovary, not using hormone therapy, and pre- or early perimenopausal at baseline, we fit piecewise linear growth curves to 5,798 repeated measurements (seven visits spanning 14.5 y) of a sexual functioning score (range, 5-25) as a function of time relative to date of final menstrual period (FMP) or hysterectomy.ResultsMean sexual functioning at baseline in women with a dateable FMP was 18.0 (SD, 3.4). There was no change in sexual function until 20 months before the FMP. From 20 months before until 1 year after the FMP, sexual function decreased by 0.35 annually (95% CI, -0.44 to -0.26) and continued to decline more than 1 year after the FMP, but at a slower rate (-0.13 annually, 95% CI, -0.17 to -0.10). The decline was smaller in African Americans and larger in Japanese than whites. Vaginal dryness, lubricant use, depressive symptoms, or anxiety did not explain decline in sexual function. Women who had a hysterectomy before the FMP did not show a decline in sexual function before hysterectomy, but scores declined afterward (0.21 annually, 95% CI, -0.28 to -0.14).ConclusionsDecline in sexual function became apparent 20 months before FMP and slowed 1 year after FMP through 5 years afterward. A decline in sexual function was observed immediately after hysterectomy and persisted for the 5 years of observation

Duration of the menopausal transition is longer in women with young age at onset

ObjectiveThe menopausal transition (MT) is a critical period associated with physiologic changes that influence women's long-term health and longevity. Information is, however, limited regarding factors that influence age at the onset of the MT and its duration (ie, time from MT onset to the final menstrual period).MethodsWe analyzed data for 1,145 women from four sites of the Study of Women's Health Across the Nation who participated in the menstrual calendar substudy, had the start of the MT identified, and had no missing covariate information. Participants included from four racial/ethnic groups: African American, white, Chinese, and Japanese. Women completed daily menstrual calendars from 1996 to 2006 and questions on hormone therapy use monthly. Baseline measures included education, economic strain, and menstrual cycle characteristics. Annual measures included height, weight, and smoking status. Cox proportional hazards models were used to analyze the data.ResultsThe adjusted median duration of the MT ranged from 4.37 years among the oldest age-at-onset quartile to 8.57 years among the youngest age-at-onset quartile (P < 0.001). Cigarette smoking was associated with an earlier onset (P < 0.001) and a shorter duration (P < 0.001). African American women had a longer duration (P = 0.012) than white women. Body mass index was associated with a later onset of the MT (P = 0.001) but not its duration.ConclusionsThe duration of the MT was largely influenced by the age at which it began: earlier onset was associated with a longer transition. This finding provides a strong rationale for developing improved markers of the onset of the early MT

Effect of Race and Ethnicity on Antihypertensive Medication Utilization Among Women in the United States: Study of Women's Health Across the Nation (SWAN)

Background: Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women. Methods and Results: Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42–52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow‐up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95% CI, 2.24–3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95% CI, 1.93–2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95% CI, 1.55–2.45) compared with whites. Use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of β‐blocker usage did not decrease over time. Conclusions: Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension

Do Changes in Sex Steroid Hormones Precede or Follow Increases in Body Weight during the Menopause Transition? Results from The Study of Women\u27s Health Across the Nation

Context: Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. Objective: The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. Design, Setting, and Participants: The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Women\u27s Health Across the Nation. Main Outcome Measures: Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. Results: Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each sd higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 sd, testosterone was higher by 0.08-0.13 sd, and log(2) FSH was lower by 0.15-0.26 sd. Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each sd higher current waist circumference, future estradiol was lower by 0.15 sd in pre- and early perimenopause and higher by 0.38 sd in late peri- and postmenopause; P for interaction Conclusions: These Study of Women\u27s Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa