Reading Between the Guidelines: How Sex Differences Impact Cardiovascular Therapy

Antiplatelet therapy is a standard of care for patients with cardiovascular diseases (CVDs). Most commonly, current practice guidelines recommend antiplatelet therapies for the secondary prevention of CVDs following a cardiovascular event. However, despite ample recommendations on the uses of antiplatelet therapies, these mediations still require additional studies.

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A review article in Platelets highlights sex differences between men and women treated with antiplatelet medications. Dissimilarities include platelet reactivity, patient management, and outcomes related to aspirin, P2Y12 inhibitors, and dual antiplatelet therapy (DAPT). The lack of evidence of sex-specific recommendations results from the underrepresentation of women in CVD-related trials. Further investigational studies on the impact of antiplatelet therapy in women can improve their cardiological care.

Key Findings of the Review Article

Platelet Reactivity. Several studies identified key differences in platelet reactivity between men and women. Women tend to have a higher density of fibrinogen binding receptors causing increased activation of the platelet signaling cascade. Furthermore, women exhibit higher platelet counts and inflammatory markers at baseline resulting in more pronounced platelet reactivity than men.

Sex Hormones. Both estrogen and progesterone influence inhibition of platelet aggregation. Cardioprotective hormones such as estrogen decline substantially after menopause. In turn, receptors that mediate platelet activation become upregulated. Unfortunately, the use of synthetic estrogens in hormone replacement does not diminish CVD risk.

Aspirin. The review article also concluded that women taking aspirin experience higher platelet reactivity compared to men taking aspirin. Researchers detect higher levels of aspirin’s metabolites (TXA2) in women, suggesting inadequate COX-1inhibition. Therefore, the article suggests clinicians consider sex for primary prevention indications, as aspirin may not lower the risk of myocardial infarction (MI) in women. However, no sufficient evidence supports sex as a consideration for secondary prevention indications.

P2Y12 Inhibitors. Detailed analysis shows clopidogrel reduces MI rates in women but reduces only stroke and mortality risk in men. Other medications in the class, such as prasugrel or ticagrelor, do not show evidence of benefit in women to the same extent in men. Researchers found these medications failed to lower the occurrence of ischemic events compared to clopidogrel.

Dual Antiplatelet Therapy (DAPT). Studies on DAPT show inconsistencies. Although many authors showed no benefit of DAPT continuation beyond 12 months due to excessive bleeding, prolonged DAPT may not be associated with bleeding in women. Therefore, clinicians should consider individual patient characteristics when deciding the duration of DAPT use.

Other Disparities Between Men and Women. In addition to some of the physiological differences and response to antiplatelet medications, women face other disparities that impact their care.

Women present with more comorbidities due to later disease onset. CVD risk increases considerably following menopause when estrogen (a cardioprotective hormone) levels drop. Women more likely face pregnancy complications, which contribute to CVD risk.

Women experience more atypical presentation to ACS, resulting in potential delays in treatment or underestimation of disease severity. Women undergo aggressive treatment or invasive surgical procedures less often than men.

The review encourages pharmacists to stay up to date with new studies and consider sex differences in all patients receiving antiplatelet therapies. Although continuing to follow current guidelines remains the best course of action, pharmacists should advocate for health care equity for the management of CVD in both men and women.

About the Author

Kimberly Ma is a 2024 PharmD candidate at the University of Connecticut.

Reference

Gasecka A, Zimodro JM, Appelman Y. Sex differences in antiplatelet therapy: state-of-the art. Platelets. 2023;34(1):2176173. doi:10.1080/09537104.2023.2176173