Do Women With Acute ACS Face Unnecessary Bleeding Risk?

Medscape

7 hours ago

A consensus statement from two European cardiology organizations contends antithrombotic treatment for myocardial infarction and angina overlooks sex differences that heighten bleeding risk in women.
Compared with men, women treated for acute coronary syndromes (ACS) are at a greater risk for in-hospital bleeding related to invasive cardiac procedures and more long-term outpatient bleeding events, according to the statement from the European Association of Percutaneous Cardiovascular Interventions and the European Society of Cardiology Working Group on Thrombosis.
Antithrombotic therapies such as heparin and fondaparinux used in invasive ACS procedures typically have a similar efficacy in women and men, but women have a higher bleeding risk of these agents, said Davide Capodanno, MD, PhD, professor of cardiology at the University of Catania, Catania, Italy, and co-author of the consensus statement. Some ways to reduce bleeding risk in women are to adjust antithrombotic dosing for body weight and kidney function, Capodanno told Medscape Medical News , and to opt for radial access over femoral access for percutaneous coronary intervention (PCI).
'Our paper shows that women still experience delays in diagnosis and treatment, receive excessive antithrombotic doses more often, and remain underrepresented in trials,' Capodanno said. 'All of this creates the need for clear, pragmatic, sex-informed recommendations.'
Physiologic Differences
Hormonal differences between men and women play an important role in bleeding risk. Estrogen promotes the production of prostacyclin, increases the availability of nitric oxide, and reduces platelet aggregation. These features might protect against the earlier onset of coronary artery disease, but fluctuations in hormonal status due to the menstrual cycle, use of oral contraceptives, menopause, and hormone replacement therapy can also influence thrombotic and bleeding risks.
Sex differences in protease-activated receptor signaling pathways, smaller coronary artery sizes, and a cascade of other factors contribute to the greater risk for bleeding associated with ACS treatment (Figure).
Although ACS typically affects postmenopausal women, the incidence is increasing in premenopausal women, whose bleeding risk is even more elevated because of lower platelet reactivity due to estrogen receptors on the platelet surface. Data from nearly 4000 women and 10,000 men undergoing PCI showed women younger than 50 years were four times more likely than men of the same age to experience major and minor bleeding events associated with stenting.
Wanted: More Sex-Specific Data
Women also often experience delays in the diagnosis of ACS and referral for invasive treatments, such as PCI, for their condition.
Clinicians still lack strong evidence to help them address sex differences in clotting and response to anticoagulation, Capodanno suggested. Awareness is improving, but there's still work to be done. 'We simply don't have enough sex-powered data to guide all our decisions. Women remain underrepresented in clinical trials, which limits the strength of sex-specific evidence,' Capodanno said. 'We need to push for more equitable research by enrolling and retaining more women in clinical studies and ensuring that results are analyzed and published separately for men and women.'
Sunil V. Rao, MD, lead author of the 2025 joint clinical practice guidelines on ACS from the American College of Cardiology and the American Heart Association, agreed. 'There are very few clinical trials of bleeding reduction that have strong female representation,' said Rao, deputy director of the Leon H. Charney Division of Cardiology and director of interventional cardiology at NYU Langone Heart in New York City.
One such study, the SAFE-PCI for Women randomized trial Rao led, compared radial access and femoral access in women undergoing stenting. The research showed using radial instead of femoral access for the intervention reduces the risk for bleeding in women.
'We need more trials like this to help guide the clinical community on how to mitigate the risks of antithrombotic therapy in women,' Rao said.
Take-Home: Male Isn't Norm
How can individual clinicians adjust their practice? 'We recommend actively reducing bleeding risk — for example, using radial access whenever possible, using ultrasound guidance if femoral access is needed, and always avoiding overdosing by adjusting for weight and kidney function,' Capodanno said.
Prompt treatment is key to avoid sex-related delays in starting antithrombotic medications. 'Also, be mindful of sex-specific presentations in ACS,' he added. Among these is myocardial infarction with nonobstructive coronary arteries, which includes spontaneous coronary artery dissection, responsible for 25%-35% of myocardial infarctions in women younger than 50 years.
According to Rao, European guidelines are generally consistent with North American recommendations with respect to antithrombotic strategies for ACS. 'I don't think we can make strong recommendations to change practice just yet,' he said. 'The message really is to counsel patients, especially female patients, on the benefit-risk balance of antithrombotic therapy, to use evidence-based approaches to reduce bleeding risk — such as radial access — and to refer female patients for clinical trials when possible.'
Capodanno reported payment for speaker fees and advisory board participation from Bristol Myers Squibb, Daiichi Sankyo, Novo Nordisk, Sanofi, and Terumo. Rao reported no relevant financial conflicts of interest.