Clot Chronicles: Women and Atrial Fibrillation

Hello, I am Dr. Annabelle Santos Volgman. I am a Professor of Medicine at Rush University Medical Center, and I’m also the McMullan-Eybel Chair for Excellence in Clinical Cardiology and the Medical Director of the Rush Heart Center for Women. Today on Clot Chronicles, I will be discussing women and atrial fibrillation (AF). My co-authors and I reviewed the sex differences in AF, and I will summarize our findings in the next few slides.

I will be using figures from my recent chapter and publications. This chapter on sex differences in AF was part of a book that was just released in February 2021 called Sex Differences in Cardiac Disease, edited by Dr. Niti Aggarwal and Dr. Malissa Wood. 

This paper was a review about women and AF that we did for the American College of Cardiology Cardiovascular Disease in Women Committee and was published in December of 2020. 

The prevalence of AF in the United States was 5.2 million in 2010 and 12.1 million are estimated to have AF in 2030. The prevalence of AF worldwide is much more – 37.6 million in 2017, with 17.8 million women and 19.8 million men worldwide. AF prevalence has been increasing in both sexes. However, on average, women live longer than men, so the number of women and men with AF are similar, despite the higher risk of AF in men. 

These are the risk factors that affect women and men with AF. There are similar risk factors for AF in women and men, but there are some sex differences. The risk factors that are similar in women and men are hypertension, advanced age, hyperthyroidism, alcohol intake, and cardiovascular disease. However, men have AF more than women when they have a prior MI, coronary artery disease, and elevated BMI or obesity. Women, however, have a higher risk of AF if they have diabetes, valvular heart disease, and elevated systolic blood pressure. 

There are definitely less women being enrolled in clinical trials. As you can see here, there are usually about 30-40% women in clinical trials for AF. These include the stroke prevention trials and the rate rhythm trials; RACE and AFFIRM predominantly included men. The treatment trials (such as antiarrhythmic drugs and catheter ablation) also predominantly include men. 

This is a table of differences in prevention and the risk of stroke in men and women. Women are less likely to receive anticoagulation – but only in the United States. Global studies show that there are no sex differences in anticoagulation for stroke prevention in AF. In 2012, when warfarin was being used more for stroke prevention than the novel anticoagulants, women spent more time outside and below the therapeutic range of warfarin. This may be the reason why women have a higher risk for stroke – and more debilitating strokes. 

This is another publication, which is a nice outline of what we found regarding unique characteristics of AF in women. So, they have a higher risk of stroke, as I mentioned, and the embolic strokes are more severe and debilitating. Women are also treated more with cardiac glycosides like digoxin, and it’s been found that these are associated with an increased risk of breast cancer and mortality. Recent studies show that the glycoside concentration digoxin concentration should be less than 1.2 to decrease that mortality risk. 

Interestingly, because women are older, they are referred less often for catheter ablation. And some studies have shown that they have more procedural complications with catheter ablation, and they have a higher recurrence rate after a catheter ablation. We already mentioned that anticoagulation use for women for stroke prevention is less in the United States (but not globally). And women have a higher risk of strokes when not on oral anticoagulants or warfarin. 

This is a left atrial appendage occluder, which we use when people have a high bleeding risk  and cannot be on anticoagulants. Women have more device-related thrombi complications from these device implantations –  but do have less bleeding when treated with these devices. 

We took a look at sex, racial, and ethnic differences in AF and published it in the Journal of the American College of Cardiology in 2019. It showed that women have less incidence of AF, and especially white women compared to white men have less lifetime risk and incidence of AF. But in blacks, women and men have the same lifetime risk, and there is a higher risk of death from AF in women and black men and women. In the same category, women and black men and women have more symptoms and poorer quality of life, so they have a longer duration of symptoms, they have more functional impairment and limitation of activities of daily living, and worse quality-of-life scores. They also have a higher risk of AF stroke risk. We found that women, blacks, and Hispanics are less likely to receive anticoagulation in the United States, and that they have more rate control than rhythm control using drugs, cardioversions, and catheter ablations. 

So, the key points I’d like to highlight are that women tend to live longer, so the lifetime incidence of AF is similar between the two sexes. Women with AF are older than men, and this may be the reason why they have an increased risk of disabling stroke. So, the older women are more likely to have other comorbidities, and they are less likely treated for rhythm control – and in the United States, get less anticoagulation therapy. Women tend to have a longer duration of symptoms, have more atypical symptoms, experience more significant functional impairment, and report worse quality of life. And the last key point is that we need to get greater representation of women in clinical trials and undertake future sex-specific research to improve the gaps in our understanding of the pathophysiologic differences, and to address disparities and improve sex-specific therapeutic approaches. Thank you. 

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