Risk-Treatment Paradox Unfortunately Alive and Well Among Young Women with ACS

Despite having high burdens of risk factors for ischemic events and bleeding, female ACS patients in their 40s and 50s who undergo PCI are less likely than their male counterparts of similar age to receive more potent antiplatelet therapy and more likely to have adverse outcomes.

Next Steps. Risk-Treatment Paradox Unfortunately Alive and Well Among Young Women with ACS

“Although these are younger women with an average age of only 48, they still have one-and-a-half times to double the prevalence of risk compared with males of the same age,” Usman Baber, MD (Icahn School of Medicine at Mount Sinai, New York, NY), told TCTMD.

He added that the risk factors mirror those seen in patients 20 years older, which is more typical of ACS presentation. “Even though the women we looked at were younger than what we typically see in studies of people who get stents, they still have a higher burden of these same risk factors compared with men,” he added. “We have to realize the difference in cardiovascular risk profile is not something that is confined to just the older population.”

PROMETHEUS Subanalysis

Finding a large enough sample size of younger men and women with ACS can be a challenge, which is why investigators used the PROMETHEUS database to look at the issue, said Baber.

PROMETHEUS was a retrospective, multicenter, observational study ofreal-world use of prasugrel (Effient; Eli Lilly) and clopidogrel in nearly 20,000 ACS patients, 32% of whom were women. Patients were treated at eight academic medical centers in the United States between January 2010 and June 2013. The study reported a variable prescribing pattern but no differences in MACE or bleeding rates at 90 days or 1 year between prasugrel and clopidogrel after adjustment.

The post-hoc sex-based analysis of PROMETHEUS—presented by Baber on May 6, 2016, at the SCAI annual scientific session in Orlando, FL, and simultaneously published in Catheterization and Cardiovascular Interventions—focused on the 4,851 patients (24% women) who were age 55 years or younger. Compared with similarly-aged men with ACS, younger women more often had diabetes, PAD, and chronic kidney disease.

Compared with clopidogrel, prasugrel was prescribed at markedly low rates overall, but was used less in women than in men (28.1% vs 31.8%; P = 0.01). Baber said the finding speaks to a practice pattern that reflects decision making in the United States.

“I think this is giving insight into natural tendencies that we as clinicians display,” he said. “We seem to be less prone to giving the stronger [antiplatelet] agent to women compared with men and the women certainly fare worse.”

At 1 year, rates of cumulative MACE were high for both sexes, but highest in women (21.1% vs 16.2%; P < 0.001). Rates of bleeding were low and similar in both treatment groups, but were higher for women (3.6% vs 2.2%; P = 0.01). The differences were no longer significant after adjustment, but Baber said the findings suggest that comorbid conditions are the drivers of the outcome differences.

Awareness, Risk Assessment Paramount

One of the most important messages of the study, Baber noted, is for clinicians to be more aware and more vigilant in assessing risk in their younger ACS patients.

Cindy Grines, MD (Detroit Medical Center, Detroit, MI), who served as a panelist at Baber’s presentation, agreed, adding that for young women, “these risk factors are preferentially harming them, and we perhaps need to be a lot more aggressive at reducing their thrombotic risk.”

Steven R. Bailey, MD (University of Texas Health Science Center, San Antonio, TX), who moderated the session, said he was struck by the relatively high incidence of MACE at 1 year in both men and women.

Baber said while younger people with ACS are probably high risk to begin with, another factor to consider is that interventional cardiologists may be more prone to “bring patients back to the lab and do [unplanned revascularizations] when they are younger.”

He said future prospective studies are needed to further understand presentation and decision making regarding younger patients with acute disease, as well those who are stable.

“It’s also going to be important to see if we can improve outcomes,” Baber observed. “The men in this study did pretty bad too, so we need to see if we can improve outcomes among all these younger patients by tailoring our decision making to give them more potent therapy upfront.”


  • The PROMETHEUS study was sponsored by Daiichi Sankyo and Eli Lilly.
  • Baber reports no relevant conflicts of interest.

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  • Chandrasekhar J, Baber U, Sartori S, et al. Sex-related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: results from the PROMETHEUS study. Catheter Cardiovasc Interv. 2016;Epub ahead of print.