Women With Afib: More Symptoms, Strokes, but Better Survival

Marlene Busko

May 19, 2016

DURHAM, NC — Compared with men with atrial fibrillation (AF), women with AF were more likely to have symptoms and a higher risk of stroke, but they were just as likely to receive anticoagulation, and "paradoxically," they were more likely to survive, in a new 2-year study[1].

These findings from an observational study of more than 10,000 patients who were part of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), by Dr Jonathan P Piccini (Duke University Medical Center, Durham, NC) and colleagues, were published online May 18, 2016 in JAMA Cardiology.

"What clinicians need to know is when they see a woman with atrial fibrillation, they are more likely to be symptomatic, and physicians need to keep that in mind when they are developing their treatment strategy for women," Dr Piccini told heartwire from Medscape. However, this was an observational study, so the key question that remains to be answered is "Why?" he stressed.

Similarly, writing in an accompanying editorial[2], Dr Rod S Passman (Northwestern University Feinberg School of Medicine, Chicago, IL), notes that this study provides insights into "the differential effects of AF between the sexes." However, although "patient registries can demonstrate what issues are worthy of future exploration . . . the findings are usually more hypothesis generating than definitive," he cautions, so this study is "just the beginning."

Little Known About Sex Differences in AF

Less is known about differences in the treatment and clinical outcomes of women vs men who have AF compared with sex-based differences for other cardiovascular diseases, Piccini and colleagues write.

They hypothesized that women with AF would have worse symptoms, lower quality of life, and worse clinical outcomes than men with AF. To investigate this, they analyzed data from ORBIT-AF, a prospective national registry of patients with AF.

They looked at data from 10,135 patients with AF who were 18 and older and seen at 176 sites in the US between June 2010 and August 2011. A subset of 2007 of these patients, seen at 99 sites, had replied to the Atrial Fibrillation Effects on Quality of Life questionnaire.

In the overall cohort, 4293 patients (42%) were women. Compared with men, more women had a left ventricular ejection fraction (LVEF) >50% (76.9% vs 65.3%), and women were older (mean age 77 vs 73) and had worse renal function and higher median CHA2DS2-VASC scores (5 vs 3) (all P<0.001).

Only three in 10 women vs four in 10 men were asymptomatic (32.1% vs 42.5%; P<0.001). Compared with men, women were more likely to report palpitations (40% vs 27%), lightheadedness (23% vs 19%), and fatigue (28% vs 25%) (all P<0.001).

In the subset of patients who replied to the AF-quality-of-life questionnaire, women had lower (worse) average scores than men (80 vs 83; P <0.001). After adjustment for baseline differences and AF-related symptoms, women were still more likely than men to have a lower quality of life (odds ratio 0.76; 95% CI 0.68–0.84; P<0.001)

In the overall cohort, compared with men, more women had prior atrioventricular nodal ablation (2.9% vs 1.7%; P<0.001) or were taking digoxin (24.6% vs 22.2%; P=0.02), but fewer women had prior AF ablation (4.9% vs 5.9%; P=0.04)or were taking a beta-blocker (62.0% vs 65.5%; P<0.001).

However, the use of antiarrhythmic and warfarin therapies and time in the therapeutic range with warfarin were similar in men and women.

Stroke-Survival Paradox

After a median follow-up of 2.3 years, women had a higher risk of stroke, but a lower risk of all-cause and cardiovascular mortality.

Risk of Outcomes in Women vs Men with AFa

Outcome HR (95% CI)b P
All-cause mortality 0.57 (0.49–0.67) <0.001
Cardiovascular mortality 0.56 (0.44–0.72) <0.001
Stroke 1.39 (1.05–1.84) 0.02
a. During a median 2.3-year follow-up
b. Adjusted for multiple baseline risk factors

"The reasons for this stroke-survival paradox are not clear; however, the paradox highlights the need for studies focused on how treatment and interventions specifically affect cardiovascular outcomes in women and men with AF," Piccini and colleagues write.

A recent meta-analysis by Emdin et al of 30 studies also reported that women with AF had a greater risk of stroke than men with AF, but in contrast to the current study, they reported that women with AF had a greater risk of cardiovascular and all-cause mortality than men with AF.

Passman notes that the current study "exposes both our progress and stagnation when it comes to AF management." Clinicians have made advances in prescribing anticoagulants since 80% of patients with CHADS2 >1 were receiving this therapy, he writes.

On the other hand, digoxin, "a drug that neither maintains sinus rhythm nor adequately controls ventricular response, was still being used to treat almost a quarter of patients." Moreover, AF ablation, "the most effective therapy for maintaining sinus rhythm . . . still appears to be underused," he continued, whereas atrioventricular node ablation, "a 'last-ditch' effort . . . was being performed maybe more than is necessary."

Piccini reports receiving a grant from Janssen Pharmaceuticals, consulting fees from Bristol-Myers Squibb/Pfizer and Johnson & Johnson; research support from ARCA Biopharma, Boston Scientific, GE Healthcare, and Johnson & Johnson/Janssen Scientific Affairs; and consultancy fees from Forest Laboratories, Janssen Scientific Affairs, Pfizer/Bristol-Myers Squibb, Spectranetics, and Medtronic. Disclosures for the coauthors are listed in the article. Passman reports serving as a consultant for Medtronic, Boehringer Ingelheim, and Janssen Pharmaceuticals; receiving research support from and being on a speakers' bureau for Medtronic; and receiving royalties for UptoDate.

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