Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab.

OBJECTIVE: To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). METHODS: This retrospective cohort study included adults with GPA (2011-2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, PJP, and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment, or Dec 31, 2020. RESULTS: Among 919 rituximab-treated individuals (53% female), mean age was 52.1 years (SD 16) and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (IQR 138, 979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI 5.0-7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted HR 0.5; 95% CI 0.3-0.9). The aHR for outpatient infections was 0.8 (95% CI 0.6-1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI 0.03-1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI 0.9-1.9). CONCLUSIONS: TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.

Differentiating Sex and Gender Among Older Men and Women.

OBJECTIVE: This study aimed to paradigmatically show the development of a gender score that can be used as either an adjustment or a matching variable to separate the effects of gender versus biological sex in a sample of older adults. METHODS: Our sample comprised 1100 participants from the Berlin Aging Study II (52% women, mean [standard deviation] age = 75.6 [3.8] years). The gender score included a multitude of gender-related variables and was constructed via logistic regression. In models of health outcomes, it was used as an adjustment variable in regression analyses as well as a matching variable to match older men and women according to their gender. RESULTS: Matching by gender substantially reduced sample size to n = 340. Analyses (either adjusting for gender or matching men and women according to gender) revealed that female sex was independently associated with lower grip strength (B = -14.47, 95% confidence interval [CI] = -15.51 to -13.44), better cognitive performance (B = 3.47, 95% CI = 1.94 to 5.0), higher pulse wave velocity (B = 0.19, 95% CI = 0.06 to 0.31), lower body mass index (B = -0.97, 95% CI = -1.74 to -0.21), and lower rates of metabolic syndrome (odds ratio = 0.53, 95% CI = 0.37 to 0.77). In addition, both sex and gender were independently associated with cognitive performance and depression. CONCLUSIONS: Calculating a gender score allows for the inclusion of a large number of variables, creating parsimonious models that are adaptable to different data sets and alternative gender definitions. Depending on the research question and the sample properties, the gender score can be used as either an adjustment or a matching variable.Trial Registration: DRKS-Deutsches Register Klinischer Studien (Study ID: DRKS00016157).

Long-term risk of stroke and bleeding post-atrial fibrillation ablation.

BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

An exploration of the subjective social status construct in patients with acute coronary syndrome.

BACKGROUND: Perception of low subjective social status (SSS) relative to others in society or in the community has been associated with increased risk of cardiovascular disease. Our objectives were to determine whether low SSS in society was associated with barriers to access to care or hospital readmission in patients with established cardiovascular disease, and whether perceptions of discordantly high SSS in the community modified this association. METHODS: We conducted a prospective cohort study from 2009 to 2013 in Canada, United States, and Switzerland in patients admitted to hospital with acute coronary syndrome (ACS). Data on access to care and SSS variables were obtained at baseline. Readmission data were obtained 12 months post-discharge. We conducted multivariable logistic regression to model the odds of access to care and readmission outcomes in those with low versus high societal SSS. RESULTS: One thousand ninety patients admitted with ACS provided both societal and community SSS rankings. The low societal SSS cohort had greater odds of reporting that their health was affected by lack of health care access (OR 1.48, 95% CI 1.11, 1.97) and of experiencing cardiac readmissions (1.88, 95% CI 1.15, 3.06). Within the low societal SSS cohort, there was a trend toward fewer access to care barriers for those with discordantly high community SSS though findings varied based on the outcome variable. There were no statistically significant differences in readmissions based on community SSS rankings. CONCLUSION: Low societal SSS is associated with increased barriers to access to care and cardiac readmissions. Though attenuated, these trends remained even when adjusting for clinical and sociodemographic factors, suggesting that perceived low societal SSS has health effects above and beyond objective socioeconomic factors. Furthermore, high community SSS may potentially mitigate the risk of experiencing barriers to access to health care in those with low societal SSS, though these associations were not statistically significant. Subjective social status relative to society versus relative to the community seem to represent distinct concepts. Insight into the differences between these two SSS constructs is imperative in the understanding of cardiovascular health and future development of public health policies.

Catheter ablation for the treatment of atrial fibrillation is associated with a reduction in health care resource utilization.

BACKGROUND: Catheter ablation (CA) is superior to antiarrhythmic therapy at reducing recurrence of atrial fibrillation (AF); however, there are limited data regarding whether this decrease translates into a reduction in health care resource utilization. OBJECTIVE: To evaluate the impact of AF ablation on long-term health care resource utilization. METHODS: A population-based cohort was constructed to include patients who underwent CA for AF in Quebec, Canada, between April 2005 and March 2011. Resource utilization was evaluated 24 months pre- and postindex CA procedure. RESULTS: In a cohort of 1,556 patients, resource utilization increased progressively over the 24-month period leading to index CA (P for trend <0.05 for hospitalizations, ER visits, outpatient visits, cardioversions, and echocardiograms). After index CA, all-cause hospitalizations, hospitalizations for AF, ER visits, cardioversions, and echocardiograms were reduced 12 months post-CA compared to 12 months prior (all-cause hospitalizations 0.8-0.6 per patient per year; hospitalizations for AF 0.4-0.3; ER visits 2.9-1.8; cardioversions 0.5-0.2; echocardiograms 0.8-0.5; P < 0.05 for all trends). Resource utilization continued to decline at 24 months post-CA (vs. 12 months prior) for all-cause hospitalizations (0.4), cardioversions (0.1), and echocardiograms (0.3) (per patient year; P < 0.05 for all trends). CONCLUSION: In conclusion, the pattern of increasing health care resource utilization preceding CA for AF reverses after CA to lower than preablation levels up to 24 months post-CA.

Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis.

BACKGROUND: Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. METHODS AND RESULTS: We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78-1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after adjusting for potential confounders. Propensity score-adjusted analyses yielded similar results. CONCLUSIONS: Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Sex differences in health behavior change after premature acute coronary syndrome.

BACKGROUND: Limited information is available on the health behavior profile of patients with premature acute coronary syndrome (ACS). The purpose of this study is to desribe the health bahvior of young patients with ACS at the baseline and 1 year post-ACS and examine sex differences. METHODS: GENESIS-PRAXY is a prospective cohort study of adults (18-55 years old) hospitalized with ACS from 26 centers located in Canada, United States, and Switzerland. Data on diet, physical activity, smoking, alcohol consumption, and recreational drug use were collected through self-administered questionnaires at baseline and 1 year post-ACS. RESULTS: Our analysis included 740 patients with complete data. At baseline, the health behavior profile of young patients with ACS was worse than that of the general population. Men had a lower fruit and vegetable intake, consumed alcohol more, and used recreational drugs more than women. Conversely, fewer men than women were smokers (34% vs 42%). At 1 year post-ACS, the proportion of those consuming ≥5 daily servings of fruits and vegetables increased modestly (+5% vs +1%, for men vs women) but remained lower than the general population. Among women, the prevalence of smoking remained about twice as high as the general population. Recreational drug use also remained higher than in the general population. CONCLUSIONS: Despite small improvements at 1 year post-ACS, the health behavior profile of young patients remained worse than that of the general population. Greater efforts to improve health behaviors post-ACS among young patients are needed, and a sex-based approach may be required to ensure successful behavioral changes.

Potential factors associated with fruit and vegetable intake after premature acute coronary syndrome: a prospective cohort study.

Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations.

Impact of Sex and Gender on Metabolic Syndrome in Adults: A Retrospective Cohort Study From the Canadian Primary Care Sentinel Surveillance Network.

OBJECTIVE: Metabolic syndrome (MetS), a cluster of 5 interconnected factors, is the main contributor to cardiovascular disease. Although sex- and gender-related elements have been linked to MetS and its components, this association has not been explored among Canadians with or without MetS. In this study, we aimed to identify sex and gender differences in characteristics of MetS in the Canadian population. METHODS: This retrospective cohort study used data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database. The CPCSSN contains de-identified electronic health records of >1.5 million Canadians (2010-2019). Individuals 35 to 75 years of age who had a primary care encounter formed the study sample (N=37,813). Multiple logistic regression models were used to estimate adjusted odds ratios for sex and gender differences among Canadians with and without MetS, which was the primary outcome variable. RESULTS: The estimated prevalence of MetS was 41.9%. The risk of developing MetS was significantly lower among females compared with males (odds ratio 0.73, 95% confidence interval 0.70 to 0.76). However, the risk was higher in females who used antidepressants (odds ratio 1.53, 95% confidence interval 1.42 to 1.65). An equal distribution of deprivation indexes was observed between males and females with MetS, with risk slightly higher for those with material deprivation. Females were found to be the most socially deprived. CONCLUSIONS: This study provides important sex- and gender-specific differences in MetS among Canadians. Targeting sex- and gender-specific risk factors could assist in reversing the trend of adverse cardiovascular outcomes associated with MetS.

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure.

BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.

Rhythm versus rate control therapy and subsequent stroke or transient ischemic attack in patients with atrial fibrillation.

BACKGROUND: Stroke is a debilitating condition with an increased risk in patients with atrial fibrillation. Although data from clinical trials suggest that both rate and rhythm control are acceptable approaches with comparable rates of mortality in the short term, it is unclear whether stroke rates differ between patients who filled prescriptions for rhythm or rate control therapy. METHODS AND RESULTS: We conducted a population-based observational study of Quebec patients ≥65 years with a diagnosis of atrial fibrillation during the period 1999 to 2007 with the use of linked administrative data from hospital discharge and prescription drug claims databases. We compared rates of stroke or transient ischemic attack (TIA) among patients using rhythm (class Ia, Ic, and III antiarrhythmics), versus rate control (ß-blockers, calcium channel blockers, and digoxin) treatment strategies (either current or new users). The cohort consisted of 16 325 patients who filled a prescription for rhythm control therapy (with or without rate control therapy) and 41 193 patients who filled a prescription for rate control therapy, with a mean follow-up of 2.8 years (maximum 8.2 years). A lower proportion of patients on rhythm control therapy than on rate control therapy had a CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or TIA) score of ≥2 (58.1% versus 67.0%, P<0.001). Treatment with any antithrombotic drug was comparable in the 2 groups (76.8% in rhythm control versus 77.8% in rate control group). Crude stroke/TIA incidence rate was lower in patients treated with rhythm control in comparison with rate control therapy (1.74 versus 2.49, per 100 person-years, P<0.001). This association was more marked in patients in the moderate- and high-risk groups for stroke according to the CHADS(2) risk score. In multivariable Cox regression analysis, rhythm control therapy was associated with a lower risk of stroke/TIA in comparison with rate control therapy (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). The lower stroke/TIA rate was confirmed in a propensity score-matched cohort. CONCLUSIONS: In comparison with rate control therapy, the use of rhythm control therapy was associated with lower rates of stroke/TIA among patients with atrial fibrillation, in particular, among those with moderate and high risk of stroke.

Access to heart failure care post emergency department visit: do we meet established benchmarks and does it matter?

BACKGROUND: The Canadian Cardiology Society recommends that patients should be seen within 2 weeks after an emergency department (ED) visit for heart failure (HF). We sought to investigate whether patients who had an ED visit for HF subsequently consult a physician within the current established benchmark, to explore factors related to physician consultation, and to examine whether delay in consultation is associated with adverse events (AEs) (death, hospitalization, or repeat ED visit). METHODS: Patients were recruited by nurses at 8 hospital EDs in Québec, Canada, and interviewed by telephone within 6 weeks of discharge and subsequently at 3 and 6 months. Clinical variables were extracted from medical charts by nurses. We used Cox regression in the analysis. RESULTS: We enrolled 410 patients (mean age 74.9 ± 11.1 years, 53% males) with a confirmed primary diagnosis of HF. Only 30% consulted with a physician within 2 weeks post-ED visit. By 4 weeks, 51% consulted a physician. Over the 6-month follow-up, 26% returned to the ED, 25% were hospitalized, and 9% died. Patients who were followed up within 4 weeks were more likely to be older and have higher education and a worse quality of life. Patients who consulted a physician within 4 weeks of ED discharge had a lower risk of AEs (hazard ratio 0.59, 95% CI 0.35-0.99). CONCLUSION: Prompt follow-up post-ED visit for HF is associated with lower risk for major AEs. Therefore, adherence to current HF guideline benchmarks for timely follow-up post-ED visit is crucial.

Sex Differences in the Effectiveness of Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Sacubitril-Valsartan for the Treatment of Heart Failure.

Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; P<0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; P<0.01; P interaction 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study.

BACKGROUND: Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). METHODS: We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. RESULTS: Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use. CONCLUSIONS: TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation.

CONTEXT: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. OBJECTIVE: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. MAIN OUTCOME MEASURES: Risk of stroke. RESULTS: The cohort comprised 39,398 men (47.2%) and 44,115 women (52.8%). At admission, women were older and had a higher CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS(2) score, and warfarin treatment. CONCLUSION: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.

Sex and Gender Influence on Cardiovascular Health in Sub-Saharan Africa: Findings from Ghana, Gambia, Mali, Guinea, and Botswana.

Background: There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Objective: To examine the associations between biological sex, gender-related variables, and cardiovascular health (CVH) risk factors in SSA countries. Methods: We used data from the STEPwise approach to surveillance of risk factors for non-communicable disease survey, conducted in adults from Ghana, Gambia, Mali, Guinea, and Botswana. The main outcome was CVH, measured through the health index with values ranging from 0 (worst) to 5 (best or ideal) CVH. Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Results: Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (ORfemale = 0.95, 95% CI:0.91-0.99). Being married was associated with better CVH compared with being single, more so for males (ORmale = 1.09, 95% CI:0.96-1.24, pinteraction < 0.01). Males with unpaid work (ORmale = 1.28, 95% CI:1.12-1.47) had better CVH than their unpaid female counterparts (ORfemale = 1.08, 95% CI:1.01-1.17). Conclusion: In SSA populations, being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females.

Cardiovascular outcomes after a change in prescription policy for clopidogrel.

BACKGROUND: Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction. METHODS: We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding. RESULTS: The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change. CONCLUSIONS: The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.

Outcomes for women and men who attend a heart failure clinic: results of a 12-month longitudinal study.

BACKGROUND: Although prevalence of heart failure (HF) is similar in women and men, more men are admitted to specialized HF clinics, possibly owing to a perception that men benefit more. Our aim was to describe 1-year outcomes in men and women attending specialized HF clinics. METHODS AND RESULTS: We enrolled 531 newly referred patients (mean age 66 years, 26% women) to 1 of 6 HF multidisciplinary clinics in Quebec. Data were collected at time of entry to the clinic and 6 and 12 months later. The 3 main outcomes, mortality, disease evolution (New York Heart Association functional class, quality of life, 6-minute walk), and number of hospital admissions/emergency department visits were analyzed separately. Survival was higher in women than in men (adjusted hazard ratio 2.53, 95% confidence interval 1.10-5.80). Both women and men improved over the 12-month period in terms of quality of life, 6-minute walk, and lower use of hospital and emergency department. Persons who at entry to the clinic had more severe disease showed more improvement. Deterioration over the year was associated with higher number of comorbidities, but not with age or gender. CONCLUSIONS: Both men and women with HF who attend specialized HF clinics improved, including those with more severe disease.

Amiodarone-induced thyroid dysfunction: brand-name versus generic formulations.

BACKGROUND: Amiodarone is associated with dysfunction of the thyroid. Concerns have arisen regarding the potential for adverse effects with generic formulations of amiodarone. We evaluated and compared the risk of thyroid dysfunction between patients using brand-name versus generic formulations of amiodarone and identified risk factors for thyroid dysfunction. METHODS: We conducted a retrospective cohort study of patients with atrial fibrillation aged 66 years and older. We used administrative databases that linked information on demographics and clinical characteristics, claims for prescription drugs and discharges from hospital. We estimated thyroid dysfunction using person-year incidence. RESULTS: Of the 60,220 patients in the cohort, 2804 (4.7%) used the brand-name formulation of amiodarone and 6278 (10.4%) used the generic formulation. Baseline characteristics between these two groups were comparable. The median maintenance dose of amiodarone was 200 mg/d for both groups. The total incidence rate for thyroid dysfunction was 14.1 per 100 person-years for both formulations. The mean time to clinical dysfunction of the thyroid was 4.32 years for the brand-name formulation and 4.09 years for the generic formulation. In a multivariate analysis, there was no significant difference in the incidence rates of thyroid dysfunction between the generic and brand formulations (hazard ratio 0.97, 95% confidence interval 0.87-1.08). Factors associated with an increased risk of thyroid dysfunction were being a woman, increasing age and having chronic obstructive pulmonary disease. INTERPRETATION: In this population-based study, we saw no difference between brand-name and generic formulations of amiodarone in terms of incidence of thyroid dysfunction.

Anticoagulant Use and the Risk of Thromboembolism and Bleeding in Postoperative Atrial Fibrillation After Noncardiac Surgery.

BACKGROUND: An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. METHODS: A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. RESULTS: We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). CONCLUSIONS: In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.