Gender-Specific Dual Antiplatelet Therapy Strategies for Women After PCI

Abstract

Dual antiplatelet therapy (DAPT) is one of the cornerstones of the management of patients after PCI and decreases the risk of stent thrombosis and adverse cardiovascular events. However, weighing up the risks of thrombosis versus bleeding represents a delicate decision, particularly because women are underrepresented in clinical studies. There is recent evidence indicating that women may benefit from shorter DAPT durations, especially those at increased bleeding risk or concomitant chronic oral anticoagulation. Although such findings are made, dedicated trials focused on women are scarce, leaving a gap in evidence-based, gender-specific guidelines. This article explores the unique thrombotic and bleeding risks in women, reviews current literature on DAPT strategies, and advocates for gender-focused research to optimize outcomes for women undergoing PCI.

Introduction

The management of CAD has been greatly improved by PCI. DAPT has become one of the cornerstones for preventing in-stent thrombosis and a variety of adverse cardiovascular events. The main challenges unique to women concern both thrombotic and bleeding risks, derived from biological differences and hormonal status, from underrepresentation in clinical studies, and the existing differences in the approach used to treat the patient. The purpose of this article is to address these gender-specific considerations, review current evidence on DAPT in women, and highlight the need for tailored approaches and future research.

The Role of DAPT After PCI

DAPT with aspirin and a P2Y12 inhibitor prevents ischemic complications by inhibiting platelet aggregation. The optimal duration of DAPT depends on individual patient risk factors, type of stent, and clinical scenarios; this is based on the risk of thrombosis versus bleeding complications. For most patients, a 6- to 12-month duration is recommended; high bleeding-risk patients may be managed with shorter regimens.

Gender-Specific Considerations in DAPT

Thrombotic Risk in Women

Women undergoing PCI often present with atypical symptoms and smaller coronary vessels, increasing procedural complexity and thrombotic risk. Additionally, hormonal fluctuations and differences in platelet reactivity may influence thrombotic profiles.

Bleeding Risk in Women

Women are more likely to experience bleeding complications during DAPT due to lower body weight, higher prevalence of anemia, and hormonal factors. The presence of comorbidities, such as chronic kidney disease and atrial fibrillation, further increases bleeding risks.

Underrepresentation in Clinical Trials

Despite comprising nearly half of CAD patients, women remain underrepresented in clinical trials evaluating DAPT. This has resulted in limited data to guide gender-specific recommendations, creating a reliance on subgroup analyses.

Current Evidence on DAPT in Women

Shortened DAPT Duration

Studies such as the STOPDAPT-2 trial have shown that shorter DAPT durations (e.g., 1–3 months) are effective in reducing bleeding risks without significantly increasing ischemic events. Subgroup analyses suggest that women, particularly those with high bleeding risks, benefit from these shortened regimens.

Chronic Oral Anticoagulation

Women with atrial fibrillation often require chronic oral anticoagulation, complicating DAPT management. Evidence supports transitioning to single antiplatelet therapy plus anticoagulation after a brief DAPT period to minimize bleeding risks.

High-Bleeding Risk Scenarios

In high-bleeding risk patients, strategies such as using newer-generation drug-eluting stents with reduced thrombogenicity allow for shortened DAPT durations. Gender-specific studies indicate that these approaches may be particularly beneficial for women.

Literature Review

Key Clinical Trials and Gender Insights

Several trials have provided insights into DAPT strategies for women:

• DAPT Trial: Demonstrated reduced ischemic events with prolonged DAPT but increased bleeding risks, highlighting the need for individualized approaches in women.

• TWILIGHT Trial: This showed that high-bleeding risk patients, including women, benefit from early aspirin discontinuation while maintaining a P2Y12 inhibitor.

• PARIS Registry: Suggested that women with shorter DAPT durations had similar thrombotic outcomes but reduced bleeding risks compared to men.

Limitations in Current Research

While these trials have advanced our understanding, their generalizability to women is limited due to underrepresentation. The lack of dedicated studies focusing on hormonal influences, comorbidities, and biological differences in women underscores the need for more inclusive research.

Challenges in Optimizing DAPT for Women

1. Clinical Complexity: Balancing thrombotic and bleeding risks in women is complicated by the presence of comorbidities and variations in platelet reactivity.

2. Treatment Disparities: Women are less likely to receive guideline-directed medical therapy, including optimal DAPT regimens.

3. Diagnostic Delays: Atypical presentation of CAD in women often leads to delays in diagnosis and treatment, impacting outcomes.

Disadvantages of DAPT in Women

While DAPT is effective in preventing thrombotic complications, it is associated with several challenges in women:

• Higher Bleeding Risks: Women have a 20–30% higher risk of major bleeding during DAPT compared to men.

• Overtreatment: Prolonged DAPT durations may expose women to unnecessary bleeding risks without additional ischemic protection.

• Lack of Personalization: Current guidelines do not fully account for gender-specific variations, leading to suboptimal treatment strategies.

Emerging Strategies and Future Directions

1. Gender-Specific Guidelines: Developing evidence-based, gender-specific guidelines for DAPT duration and regimen selection is essential to optimize outcomes in women.

2. Personalized Medicine: Integrating clinical, genetic, and hormonal factors into risk assessment tools can aid in tailoring DAPT strategies for women.

3. Dedicated Clinical Trials: Conducting trials exclusively enrolling women is critical to addressing knowledge gaps and validating gender-specific recommendations.

4. Role of Biomarkers: Investigating gender-specific biomarkers, such as platelet reactivity indices, may help predict thrombotic and bleeding risks in women.

Conclusion

Dual antiplatelet therapy forms the cornerstone of post-PCI care, but its application in women poses distinct challenges. The higher risk of bleeding and disparity in treatment underlines the importance of a customized approach. The promising strategy in the form of shorter DAPT durations, particularly for high-bleeding risk women, remains to be validated through dedicated research. Advances in our knowledge of gender-specific differences and the application of tailored DAPT regimens may improve the outcomes and minimize complications in female patients undergoing PCI. Addressing these gaps would help ensure fair and effective cardiovascular care for all patients.

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