Understanding Sex Disparities in Heart Disease, Stroke is a Major Research Priority

Understanding the sex differences in cardiovascular disease presentation and outcomes remains a major research priority, according to the American Heart Association (AHA).

In fact, the Go Red for Women special issue of AHA’s journal Circulation includes numerous studies on the topic, after more than 100 manuscripts were submitted this year.¹

“Undeniably, cardiovascular disease remains the number 1 killer of women around the world, taking the lives of 1 in 3 women. Even 1 life lost is too many, because we know much of heart disease and stroke is preventable and treatable,” said Joseph A. Hill, MD, PhD, editor-in-chief of Circulation, in a news release.²

“Support for ongoing research, as well as female participation in pivotal clinical trials, are imperative to effectively address sex disparities in heart disease and stroke care as part of our effort to improve cardiovascular health for women,” Hill continued. “These are critical in our fight against heart disease and stroke in women.”

One of the important studies highlighted in the Go Red for Women issue was a comparison of the efficacy and safety outcomes of edoxaban (Lixiana) with warfarin in 8040 women versus 13,065 men with atrial fibrillation (AFib).³

Researchers examined clinical trial data involving more than 21,000 patients (8040 women) with AFib and an elevated risk for stroke. They were randomized to a higher dose or a lower dose of the newer anticoagulant edoxaban or to warfarin, “which is an older anticoagulant that must be closely monitored and tends to carry some risks,” AHA said in its news release.² Follow-up continued for around 3 years.

At baseline, women had a higher level of FXa activity—a critical protein in the clotting process—placing women at potentially increased risk of thrombosis relative to men. Treatment with high-dose edoxaban reduced FXa levels to a greater extent in women than in men, resulting in similar intensity of anticoagulation.³

Compared to warfarin, the treatment effect of the higher dose of edoxaban on the risk of stroke or other major clotting events and on major bleeding was similar in women and men.³

However, the high-dose edoxaban reduced the risk of severe bleeding outcomes, including hemorrhagic stroke, to a greater extent in women than in men, AHA said.² “Researchers said the safety advantage of edoxaban in women is enhanced for multiple bleeding end points compared with men, suggesting that edoxaban is a particularly attractive option for the treatment of women with [AFib].”

Another major study examined the association between sex and treatment outcomes of AFib ablation versus drug therapy.⁴

Researchers randomized 2204 patients with AFib (37% women) who were 65 or older or were under age 65 but had at least 1 risk factor for stroke to receive treatment with either catheter ablation or drug therapy to control heart rhythm. There was no significant difference in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest in men versus women, they reported.⁴

Adverse events related to either therapy were low in both men and women, without significant sex differences. Catheter ablation compared with drug therapy reduced AF recurrence in both men and women.⁴

“Whereas prior nonrandomized data have suggested higher procedural complications in women compared with men, this was not seen in this randomized trial. Researchers said recommendations for ablation should not be discouraged based on concern for adverse events in women, and since ablation offers comparable benefits for women and men, sex should not be used as a basis for selecting a management strategy for treatment of AFib,” AHA said in its news release.²

References:

1. American Heart Association. AHA Journals Go Red for Women Collection.. https://www.ahajournals.org/go-red

2. Understanding heart disease, stroke in women remains a scientific research priority. News release. American Heart Association; February 15, 2021. Accessed March 2, 2021. https://newsroom.heart.org/news/understanding-heart-disease-stroke-in-women-remains-a-scientific-research-priority.

3. Zelniker T, Ardissino M, Andreotti F, et al. Comparison of the efficacy and safety outcomes of edoxaban in 8040 women versus 13,065 men with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. Circulation. 2021. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052216

4. Russo A, Zeitler E, Giczewska A, et al. Association between sex and treatment outcomes of atrial fibrillation ablation versus drug therapy: Results from the CABANA Trial. Circulation. 2021. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.051558.