Sex Differences in Treatment Strategy and Adverse Outcomes Among Patients 75 and Older With Atrial Fibrillation in the MarketScan Database

Abstract Background: Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed.Methods: We studied 135,850 men and 139,767 women aged ≥75 years diagnosed with AF in the MarketScan Medicare database between 2007-2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results: At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95%CI 1.34-1.49; HR men= 1.21, 95%CI 1.15-1.28, p <0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. Conclusion: Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

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Sex differences in treatment strategy and adverse outcomes among patients 75 and older with atrial fibrillation in the MarketScan database

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02419-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Vinita Subramanya ◽

J’Neka S. Claxton ◽

Pamela L. Lutsey ◽

Richard F. MacLehose ◽

Lin Y. Chen ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Sex Differences ◽

Rate Control ◽

Treatment Strategy ◽

Cox Regression ◽

Rhythm Control ◽

Adverse Outcomes ◽

Control Treatment ◽

To Receive

Abstract Background Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. Methods We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34–1.49; HR men = 1.21, 95% CI 1.15–1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. Conclusion Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

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Abstract P111: Sex Differences in Rate or Rhythm Control and Outcomes Among Elderly Patients With Atrial Fibrillation

Circulation ◽

10.1161/circ.141.suppl_1.p111 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Vinita Subramanya ◽

J'Neka S Claxton ◽

Pamela L Lutsey ◽

Richard MacLehose ◽

Alanna M Chamberlain ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Elderly Patients ◽

Major Bleeding ◽

Rate Control ◽

Treatment Strategy ◽

Cox Regression ◽

Rhythm Control ◽

To Receive

Introduction: Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control for the treatment of AF. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. Methods: We studied 135,850 men and 139,767 women 75 years or older diagnosed with AF in the MarketScan Medicare database between 2007-2015. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmics, catheter ablation or cardioversion. Participants on both rate and rhythm were coded under rhythm control. We used multivariable logistic and Cox regression models to estimate 1) the association of sex and treatment strategy (within 30-day post AF diagnosis and entire follow-up) and, 2) the association of treatment strategy with incident heart failure, stroke and major bleeding. Results: Men were on average (SD) 82.5 (5.2) years old and women 83.8 (5.6) years, respectively. Women were less likely to receive rhythm control treatment as compared to men in the 30-day post AF diagnosis period (22% vs 27%), (OR 0.91, 95% CI 0.88, 0.94) and over the entire duration of follow-up (28% vs 32%) (HR 0.93, 95% CI 0.90, 0.96). Rhythm (vs. rate) control was associated with a higher risk of heart failure in women [HR 1.41, 95% CI 1.34, 1.49] than in men [HR, 1.21 95% CI 1.15, 1.28] (p for multiplicative interaction < 0.001, Table ). Sex did not modify associations between treatment and incident stroke or major bleeding events. Conclusion: Women aged 75 years and older were less likely to be prescribed rhythm control as compared to men, and experienced higher risk of heart failure than men when receiving rhythm (vs rate) control. Future studies will need to delve into the mechanisms underlying these differences.

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Gender-Related Differences In Treatment Patterns And Outcomes of Patients With Atrial Fibrillation: Insights From The MISOAC-AF Trial

10.21203/rs.3.rs-772332/v1 ◽

2021 ◽

Author(s):

Ioannis Vouloagkas ◽

Anastasios Kartas ◽

Athanasios Samaras ◽

Andreas S. Papazoglou ◽

Dimitrios V. Moysidis ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Rate Control ◽

Cox Regression ◽

Cardiovascular Death ◽

Treatment Patterns ◽

Rhythm Control ◽

Vitamin K Antagonist ◽

Control Treatment ◽

All Cause Mortality

Abstract PurposeTo assess the gender-related differences in the treatment patterns of patients with atrial fibrillation (AF), and their prognostic value.MethodsIn this post-hoc analysis of a randomized controlled trial, 1140 hospitalized patients with comorbid AF were followed-up for a median of 2.6 years. Kaplan-Meier and multivariable Cox-regression analyses assessed the adjusted hazard ratios (aHRs) for outcomes in males and females, according to oral anticoagulation (OAC) type (vitamin K antagonist or non-vitamin K antagonist oral anticoagulants), rhythm or rate control treatment. The primary outcome was all-cause mortality and the secondary outcomes were stroke and the composite of any hospitalization or cardiovascular death. ResultsAmong 622 males and 518 females, use of OAC (61% vs 62%), rate control (56% vs 57%), and rhythm control (31% vs 28%) treatments was similar (all p>0.05). In males, use of rate control, as compared with rhythm control, was independently associated with higher rates of all-cause mortality (aHR=2.06; 95% confidence interval [CI] 1.24-3.41) and the composite of hospitalization or cardiovascular death (aHR=1.34, 95% CI 1.01-1.85). In females, use of rhythm control was significantly associated with higher rates of hospitalization-or cardiovascular mortality (aHR=1.74, 95% CI 1.03-2.94). Among genders, stroke rates were similar regardless of OAC type, rate or rhythm control treatment.ConclusionsIn patients discharged from the hospital with comorbid AF, the use of OAC, rhythm or rate control treatment was similar among genders. However, males seemed to benefit more from rhythm, whereas females from rate control treatment.

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Comparative Effectiveness of Early Rhythm Control Versus Rate Control for Cardiovascular Outcomes in Patients With Atrial Fibrillation

Journal of the American Heart Association ◽

10.1161/jaha.121.023055 ◽

2021 ◽

Author(s):

Daehoon Kim ◽

Pil‐Sung Yang ◽

Seng Chan You ◽

Eunsun Jang ◽

Hee Tae Yu ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Atrial Fibrillation ◽

Rate Control ◽

Cardiovascular Death ◽

Population Based ◽

Cardiovascular Outcomes ◽

Rhythm Control ◽

Control Treatment ◽

Control Rhythm

Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients with recently diagnosed atrial fibrillation (AF). This study investigated the effects of rhythm control compared with rate control on the incidence of stroke, heart failure, myocardial infarction, and cardiovascular death stratified by timing of treatment initiation. Methods and Results We conducted a retrospective population‐based cohort study including 22 635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011 to 2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Compared with rate control, rhythm control initiated within 1 year of AF diagnosis decreased the risk of stroke. The point estimates for rhythm control initiated at selected time points after AF diagnosis are as follows: 6 months (hazard ratio [HR], 0.76; 95% CI, 0.66–0.87), 1 year (HR, 0.78; 95% CI, 0.66–0.93), and 5 years (HR, 1.00; 95% CI, 0.45–2.24). The initiation of rhythm control within 6 months of AF diagnosis reduced the risk of hospitalization for heart failure: 6 months (HR, 0.84; 95% CI, 0.74–0.95), 1 year (HR, 0.96; 95% CI, 0.82–1.13), and 5 years (HR, 2.88; 95% CI, 1.34–6.17). The risks of myocardial infarction and cardiovascular death did not differ between rhythm and rate control regardless of treatment timing. Conclusions Early initiation of rhythm control was associated with a lower risk of stroke and heart failure–related admission than rate control in patients with recently diagnosed AF. The effects were attenuated as initiating the rhythm control treatment later.

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Faculty Opinions recommendation of Rhythm control versus rate control for atrial fibrillation and heart failure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115293.575938 ◽

2008 ◽

Author(s):

Hector Ventura ◽

Anil Verma

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Rate Control ◽

Rhythm Control ◽

Control Versus

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Sex Differences in the Association between Atrial Fibrillation and 90-Day Adverse Outcomes among Older Adults with Heart Failure: A Retrospective Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052237 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2237

Author(s):

Youn-Jung Son ◽

Da-Young Kim ◽

Mi Hwa Won

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Older Adults ◽

Sex Differences ◽

Older Adult ◽

Hospital Readmission ◽

Older Patients ◽

Adverse Outcomes ◽

Prognostic Impact ◽

Male And Female

Sex differences in the prognostic impact of coexisting atrial fibrillation (AF) in older patients with heart failure (HF) have not been well-studied. This study, therefore, compared sex differences in the association between AF and its 90-day adverse outcomes (hospital readmissions and emergency room (ER) visits) among older adults with HF. Of the 250 older adult patients, the prevalence rates of coexisting AF between male and female HF patients were 46.0% and 31.0%, respectively. In both male and female older patients, patients with AF have a significantly higher readmission rate (male 46.0%, and female 34.3%) than those without AF (male 6.8%, and female 12.8%). However, there are no significant differences in the association between AF and ER visits in both male and female older HF patients. The multivariate logistic analysis showed that coexisting AF significantly increased the risk of 90-day hospital readmission in both male and female older patients. In addition, older age in males and longer periods of time after an HF diagnosis in females were associated with an increased risk of hospital readmission. Consequently, prospective cohort studies are needed to identify the impact of coexisting AF on short- and long-term outcomes in older adult HF patients by sex.

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Abstract P369: Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Elderly Patients With Atrial Fibrillation

Circulation ◽

10.1161/circ.141.suppl_1.p369 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Cited By ~ 1

Author(s):

Aniqa Alam ◽

Nemin Chen ◽

Pamela L Lutsey ◽

Richard MacLehose ◽

J'Neka Claxton ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Elderly Patients ◽

Rate Control ◽

Treatment Effectiveness ◽

Adverse Outcomes ◽

Pharmacy Claims ◽

Increased Risk ◽

The Impact

Background: Polypharmacy is highly prevalent in elderly individuals with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly AF patients remains unaddressed. Methods: We studied 338,810 AF patients ≥75 years of age with 1,761,660 active prescriptions [mean (SD), 5.1 (3.8) per patient] enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular endpoints (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular endpoints and the interaction between polypharmacy and AF treatments in relation to cardiovascular endpoints. Results: Prevalence of polypharmacy was 52% (176,007 of 338,810). Patients with polypharmacy had increased risk of major bleeding [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12, 1.20] and heart failure (HR 1.33, 95%CI 1.29, 1.36), but not of ischemic stroke (HR 0.96, 95%CI 0.92, 1.00), compared to those not with polypharmacy (Table). Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. However, rhythm control (vs. rate control) was more effective in preventing heart failure hospitalization in patients not with polypharmacy (HR 0.87, 95%CI 0.76, 0.99) than among those with polypharmacy (HR 0.98, 95%CI 0.91, 1.07, p for interaction = 0.02). Conclusion: Polypharmacy is frequent among elderly patients with AF, associated with adverse outcomes, and potentially affecting the effectiveness of AF treatments. Optimizing management of polypharmacy in elderly AF patients may lead to improved outcomes.

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3153Rate versus rhythm control and mortality in atrial fibrillation patients: a Danish nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.0041 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Dalgaard ◽

S Al-Khatib ◽

J Pallisgaard ◽

C Torp-Pedersen ◽

T B Lindhardt ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Disease ◽

Control Strategy ◽

Rate Control ◽

Channel Blocker ◽

Rhythm Control ◽

All Cause Mortality ◽

Control Therapy

Abstract Background Treatment of AF patients with rate or rhythm drug therapy have shown no difference in mortality in clinical trials. However, the generalizability of these trials to real-world populations can be questioned. Purpose We aimed to investigate the all-cause and cardiovascular (CV) mortality risk in a nationwide AF cohort by treatment strategy (rate vs. rhythm) and by individual drug classes. Methods We queried the Danish nationwide registries from 2000 to 2015 to identify patients with AF. A rate control strategy included the use of one or more of the following medications: beta-blocker, digoxin, and a class-4 calcium channel blocker (CCB). A rhythm control strategy included the use of an anti-arrhythmic drug (amiodarone and class-1C). Primary outcome was all-cause mortality. Secondary outcome was CV mortality. Adjusted incidence rate ratios (IRR) were computed using Poisson regression with time-dependent covariates allowing patients to switch treatment during follow-up. Results Of 140,697 AF patients, 131,793 were on rate control therapy and n=8,904 were on rhythm control therapy. At baseline, patients on rhythm control therapy were younger (71 yrs [IQR: 62–78] vs 74 [65–82], p<0.001) more likely male (63.5% vs 51.7% p<0.001), had more prevalent heart failure (31.1% vs 19.4%, p<0.001) and ischemic heart disease (40.1% vs. 23.3%, p<0.001), and had more prior CV-related procedures; PCI (7.4% vs. 4.0% p<0.001) and CABG (15.0% vs. 2.3%, p<0.001). During a median follow up of 4.0 (IQR: 1.7–7.3) years, there were 64,653 (46.0%) deaths from any-cause, of which 27,025 (19.2%) were CVD deaths. After appropriate adjustments and compared to rate control therapy, we found a lower IRR of mortality and CV mortality in those treated with rhythm control therapy (IRR: 0.93 [95% CI: 0.90–0.97] and IRR 0.84 [95% CI: 0.79–0.90]). Compared with beta-blockers, digoxin was associated with increased risk of all-cause and CV mortality (IRR: 1.26 [95% CI: 1.24–1.29] and IRR: 1.32 [95% CI: 1.28–1.36]), so was amiodarone: IRR for all-cause mortality: 1.16 [95% CI: 1.11–1.21] and IRR for CV mortality: 1.12 [95% CI: 1.05–1.19]. Class-1C was associated with lower all-cause (0.43 [95% CI: 0.37–0.49]) and CV mortality (0.35 [95% CI: 0.28–0.44]). Figure 1. Models were adjusted for age, sex, ischemic heart disease, stroke, chronic obstructive pulmonary disease, chronic kidney disease, valvular atrial fibrillation, bleeding, diabetes, ablation, pacemaker, implantable cardioverter defibrillator, hypertension, heart failure, use of loop diuretics, calendar year, and time on treatment. Abbreviations; CCB; calcium channel blocker, PY; person years. Conclusions In a real-world AF cohort, we found that compared with rate control therapy, rhythm control therapy was associated with a lower risk of all-cause and CV mortality. The reduced mortality risk with rhythm therapy could reflect an appropriate patient selection. Acknowledgement/Funding The Danish Heart Foundation

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