High-quality real-world registry data can reveal gender differences in how patients develop stroke and respond to treatments. As the power of these data becomes increasingly apparent, we must adapt our regulatory and clinical guideline [Citation1] approach to take account of this new and increasingly robust form of evidence.
Stroke is a serious global health problem: every year, an estimated 15 million people are affected [Citation2]. Of these, around five million die and millions more suffer serious reductions in quality of life. Atrial fibrillation (AF) is a major risk factor for ischemic stroke [Citation3]. The risk of experiencing stroke is up to five times higher in people with AF compared to those without AF [Citation4].
Gender differences are also apparent in the risk of AF and the prognosis for patients with AF. Recent evidence has increased awareness of gender differences while also highlighting some of the gaps in our knowledge (see ) [Citation5].
Figure 1. Overview of atrial fibrillation in women compared with in men (Adapted from Ko et al. [Citation5]).
![Figure 1. Overview of atrial fibrillation in women compared with in men (Adapted from Ko et al. [Citation5]).](/cms/asset/5bbd36fa-e023-4b2e-a247-0f16eb70384b/ierk_a_1353420_f0001_oc.jpg)
Women generally have a lower age-adjusted incidence and prevalence of AF than men but, because prevalence of AF increases with age, more elderly patients with AF are women [Citation6]. However, women with AF are more likely to present with symptoms including weakness, fatigue, dyspnea, palpitations, light-headedness, and chest discomfort. They will often experience symptoms for longer than men, leading to a poorer quality of life. Women with AF also have a higher prevalence of hypertension, vascular disease, and valvular heart disease, and are at increased risk of AF-related stroke and thromboembolism compared with men.
There may also be differences in outcomes for men and women treated with oral anticoagulants. This has been seen in clinical trials and in registry data. For example, results from the ROCKET-AF trial found slightly higher rates of stroke in women compared with men with AF during a phase III trial of anticoagulant therapies [Citation7]. On the other hand, women experienced lower rates of vascular death and myocardial infarction compared with men [Citation8].
It has been shown that women with AF taking warfarin are at greater residual risk of cerebrovascular accident/systemic embolism (CVA/SE) compared with men but no gender difference in residual risk of CVA/SE was noted in patients with AF receiving novel oral anticoagulants [Citation9].
Data from the ORBIT-AF registry suggest that women with AF are at increased risk of stroke, but with a decreased risk of cardiovascular mortality and all-cause mortality compared with men [Citation10]. The ORBIT-AF registry also showed that compared with men, women with AF have more clinical symptoms and more functional limitations.
The gender differences are plain to see. What is less clear are the reasons behind the variation in prevalence and prognosis. In particular, differences in patients’ outcomes while on anticoagulation therapy demands an in-depth exploration. The above examples of the contribution that registries make should inspire us to build larger and more robust datasets to help us understand the gender differences that have been observed.
1. Contribution of the GARFIELD-AF registry
Much of the groundwork has already been done. The GARFIELD-AF registry, a worldwide noninterventional program aims to deepen our understanding of AF, bridging the gap between research and clinical practice. A total of 57,262 patients have been enrolled and the registry is bearing fruit in the form of high-quality peer-reviewed papers. Crucially, the registry is audited and independently validated, ensuring the highest standards of evidence generation.
Earlier this year, I coauthored a paper exploring the impact of gender, risk factors, and anticoagulant treatment on 1-year outcomes in patients with AF [Citation11]. We found that women had a higher risk of stroke/SE, but the reduction of stroke/SE rates with anticoagulant treatment was less in women than in men. Compared with no treatment, anticoagulation treatment lowered the risk of stroke/SE to a greater extent in men than women: hazard ratio 0.77 (95% confidence interval 0.57–1.03) and this interaction was significant (p = 0.001).
These analyses provide valuable insights into stroke prevention in men and women in the real-world setting and suggest that women are less well anticoagulated. However, the reasons for these differences require further exploration using data from GARFIELD-AF. The registry is the largest prospective, ongoing, noninterventional, multicenter study of patients aged over 18 years with newly diagnosed non-valvular AF and at least one stroke risk factor. By August 2017, at least 1-year follow-up data will be available for more than 51,000 patients. Most importantly, the findings are based on real-world data. GARFIELD-AF is a unique database and well suited to studying these questions in detail, including assessing gender-specific prescribing practice as well as differences in adherence to anticoagulation therapies and quality of anticoagulation control.
In conclusion, as real-world evidence emerges from registries, medicines licensing authorities and scientific societies will need to adapt. The days of relying solely on randomized clinical trial data must end. With the availability of audited registry data with the power to answer gender-specific questions, clinical guidelines must continue to reflect the differences in how women and men respond to interventions.
Declaration of interest
The author is a member of the Steering Committee for the GARFIELD-AF Registry, which is sponsored by the Thrombosis Research Institute and supported by an unrestricted educational grant from Bayer AG, Berlin, Germany. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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References
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