Meytal Avgil Tsadok

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 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 Differences in Acute Coronary Syndrome Symptom Presentation in Young Patients

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.

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 (&bgr;-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 CHADS2 (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 CHADS2 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.

Sex-related differences in access to care among patients with premature acute coronary syndrome

Background: Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care. Methods: We studied 1123 patients (18–55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures. Results: Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non–ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework. Interpretation: Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Sex Differences in Dabigatran Use, Safety, And Effectiveness In a Population-Based Cohort of Patients With Atrial Fibrillation

Background—Sex differences were observed with regard to warfarin treatment in patients with atrial fibrillation, with women having a higher risk of stroke compared with men. We aimed to compare sex differences in use, safety, and effectiveness of dabigatran. Methods and Results—We conducted a population-based cohort study of patients with atrial fibrillation using administrative data in Quebec, Canada, 1999 to 2013. Men and women who filled a prescription for dabigatran (110 and 150 mg bid) were compared with matched warfarin users with respect to their rates of stroke, bleeding, and myocardial infarction events, using propensity score analysis. The cohort comprised 31 786 women (50.4%) and 31 324 men (49.6%). Women had a higher baseline stroke risk and lower baseline bleeding risk compared with men. Women filled more prescriptions for the lower dabigatran dose compared with men (adjusted OR, 1.35; 95% confidence interval, 1.24–1.48). In multivariable analyses adjusted for propensity scores, dabigatran use was associated with a lower risk of bleeding compared with warfarin in men (P for interaction=0.008). Dabigatran was associated with a trend toward lower risk of stroke in women treated with the 150-mg dose (HR, 0.79; 95% confidence interval, 0.56–1.04), but was not associated with a difference in the risk of myocardial infarction compared with warfarin in either sex. Conclusions—In real-life practice, women are more frequently treated with low-dose dabigatran, yet a trend toward lower stroke rates in women taking high-dose dabigatran was observed. Men benefit from lower bleeding rates with dabigatran compared with warfarin.

Temporal trends and sex differences in pulmonary vein isolation for patients with atrial fibrillation

BACKGROUND Indications for pulmonary vein isolation for the treatment of atrial fibrillation (AF) have expanded over the years. OBJECTIVE We aimed to describe trends in demographic and clinical characteristics of patients undergoing ablation, with a particular focus on sex differences. METHODS Patients who underwent first AF ablation between 2003 and 2012 were identified within an AF cohort by using Quebec administrative databases. Descriptive statistics and multivariable analysis were used to examine sex differences and temporal trends in demographic and clinical characteristics, as well as independent predictors of the ablation procedure. RESULTS A total of 2438 of 173,689 patients in the AF cohort underwent AF ablation. In the span of 10 years, the rate of AF ablation increased from 8.5 to 57.2 per million persons-an almost 7-fold increase. Patients undergoing ablation were younger than patients in the general AF cohort (57.4 ± 12.2 years vs 75.3 ± 12.0 years) and had fewer baseline comorbidities (56.7% vs 88.4%). Representing 42.9% of the general AF cohort, the annual proportion of women in the AF ablation cohort has not surpassed 30%, and men had a higher likelihood of undergoing ablation than did women (odds ratio 1.54; 95% confidence interval 1.40-1.69). Over the decade of observation, there were slight increases in patient age, comorbidities, and CHADS2 score, some of which reached clinical significance for men and/or women. CONCLUSION The uptake of AF ablation over 10 years has expanded, with an increasingly greater number of older patients and with increased presence of comorbidities; however, there has been no increase in the relatively low proportion of women undergoing AF ablation.

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.

Comparison of the Effect of Thiazide Diuretics and Other Antihypertensive Drugs on Central Blood Pressure: Cross-Sectional Analysis Among Nondiabetic Patients

Thiazide diuretics (TDs) are a cost‐effective first‐line therapy for uncomplicated hypertension; however, they are less prescribed than other options. The authors aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to central blood pressure. Cross‐sectional data from the Quebec CARTaGENE project was used. Nondiabetic hypertensive participants on monotherapy for hypertension were studied. Separate adjusted models were constructed to establish noninferiority of TDs to non‐TD antihypertensive medications for central blood pressure measurements. Models included a set of potential confounders. Of the 1194 hypertensive participants, 7.4% were taking TDs. We found that TDs were comparable with non‐TD antihypertensive medications for central systolic blood pressure (adjusted regression coefficient, 0.45; 95% confidence interval, −1.61 to 2.50). No differences in other central measurements were noted. The results provide additional support that TDs are at least as effective as other first‐line medications for treating uncomplicated hypertension.

Sex differences in prodromal symptoms in acute coronary syndrome in patients aged 55 years or younger

Background Studies suggest that young women are at highest risk for failing to recognise early symptoms of acute coronary syndrome (ACS). Objectives To examine sex differences in prodromal symptoms occurring days and weeks prior to the acute presentation of ACS. We also examined health-seeking behaviours and prehospital management in young patients. Methods Prospective cross-sectional analysis of 1145 patients (368 women) hospitalised for ACS, aged ≤55 years, from the GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary SYndrome cohort study (January 2009–April 2013). Prodromal symptoms were determined using the McSweeney Acute and Prodromal Myocardial Infarction Symptom questionnaire. Health-seeking behaviour and prehospital care were determined by questionnaires. Results The median age was 49 years. The prevalence of prodromal symptoms was high and more women reported symptoms than men (85% vs 72%, p<0.0001). Symptoms were similar between sexes and included unusual fatigue, sleep disturbances, anxiety and arm weakness/discomfort. Chest pain was less common in both sexes (24%). Women were more likely to seek care (49% vs 42%, p=0.04). Among those who sought care, women were more likely to use an ambulance for their ACS compared with men (52% vs 39%). Cardiovascular risk-reduction therapy use was low (≤40%) in all patients and less than half perceived their care provider suspected a cardiac source. Conclusions Prior to ACS, women were more likely to experience prodromal symptoms and seek medical attention than men. Prehospital care was generally similar between sexes but demonstrated underutilisation of risk-reduction therapies in at-risk young adults.