Women Less Likely to Receive Evidence-Based Therapies Than Men

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Women with acute coronary syndromes (ACS) are less likely to receive proven cardiovascular medications than men, according to a large Canadian registry study. In some cases this is the result of factors such as age or physician reluctance to perform cardiac catheterization, while in others female sex remains the sole reason, according to findings published online March 7, 2011, ahead of print in the European Heart Journal.

Researchers led by Raffaele Bugiardini, MD, of the University of Bologna (Bologna, Italy), analyzed 6,558 ACS patients (4,471 men, 2,087 women) from over 50 hospitals enrolled in the prospective Canadian ACS Registry I and II to investigate treatment disparities between men and women and the factors that may predispose to them.

Women in the study were older and had more hypertension and history of heart failure. They also presented less frequently with Killip class 1 and positive troponin, and underwent fewer invasive procedures including angiography, PCI, and CABG compared with men. Women also had worse outcomes, experiencing higher mortality rates at both discharge (3.4% vs. 2.2%; P = 0.0078) and 1 year (10.5% vs. 8.0%; P = 0.0017) compared with men.

At discharge, women were 18% less likely to receive beta-blockers, 32% less likely to receive lipid-modifying agents, and 17% less likely to receive ACE inhibitors than men, while the rates of antiplatelet agents were equivalent (table 1).

Table 1. Medications at Discharge


(n = 4,471)

(n = 2,087)

P Value

Antiplatelet Agents








Lipid-Modifying Agents



< 0.0001

ACE Inhibitors





On multivariable analysis, different factors contributed to women’s reduced likelihood to receive medications depending on the type of agent. For beta-blockers, negative predictors for prescribing in women included:

  • Older age (OR 0.95; 95% CI 0.92-0.98)
  • Killip class 2 (OR 0.67; 95% CI 0.60-0.81)
  • Killip class 3/4 (OR 0.61; 95% CI 0.44-0.85)
  • Higher heart rate (OR 0.95; 95% CI 0.92-0.98)

For ACE inhibitors, negative predictors in women included:

  • Increasing creatinine levels (OR 0.67; 95% CI 0.54-0.88)
  • No referral to cardiac catheterization (OR 0.83; 95% CI 0.66-0.98)
  • CABG during hospitalization (OR 0.68; 95% CI 0.54-0.88)
  • Female sex (OR 0.74; 95% CI 0.65-0.83)

Independent negative predictors for prescribing of lipid-lowering agents in women included:

  • Older age (OR 0.80; 95% CI 0.75-0.84)
  • Female sex (OR 0.77; 95% CI 0.66-0.88)
  • No referral to cardiac catheterization (OR 0.42; 95% CI 0.14-0.65)

“The findings demonstrate an underutilization of evidence-based treatments in women with ACS,” the researchers conclude. “This disparity appears to depend largely upon multiple factors related to the patient (age), to consequences of the disease (congestive heart failure), and to the physician’s assessment of patient risk (decision to catheterize).”

In the study, women received cardiac catheterization less often than men (41.8% vs. 49.6%; P < 0.0001), and this was an independent predictor of underprescribing for both ACE inhibitors and lipid-modifying agents. The authors point out that because all study patients had a diagnosis of ACS, they should have received equal consideration and evidence-based treatments.

Just Being Female Reason to Underprescribe

Even after adjusting for all other confounders, female sex remained an important negative predictor. In the case of lipid-lowering agents, a potential explanation may lie in the fact that female sex is a main independent predictor of the absence of obstructive CAD, the authors note, which may cause physicians to hesitate in prescribing drugs such as statins. The case of ACE inhibitors, however, is more puzzling, since women presented with more heart failure and a history of hypertension and were likely to benefit from the drugs.

“Women with heart attacks have higher death rates than men, so these findings are very concerning, and it's important for us to try to figure out why this is happening,” commented Dr. Bugiardini in an e-mail communication with TCTMD. “It seems likely that a more aggressive medical intervention would have resulted in better outcomes.”

He stressed that the differences in medication prescribing are clinically meaningful. In an interview with TCTMD, Kimberly A. Skelding, MD, of Geisinger Medical Center (Danville, PA), agreed. “Absolutely. We’re not talking about nitroglycerin usage, we’re talking about medications that have been shown to improve both quality and length of life,” she said.

Failure to Cath Tied to Underestimation of Risk

Dr. Skelding added that the results “weren’t terribly surprising, because we know that women get less evidence-based therapies. So we find that there’s less use of beta-blockers and ACE inhibitors, which are really life-saving medications. And in addition, women are less often getting referred for catheterization, which is probably a surrogate for people thinking that women are at lower risk and don’t need an invasive evaluation.”

Dr. Bugiardini pointed to one simple reason to explain these disparities. “This evidence clearly implicates physician bias as a contributor,” he said. “However, the nature of this bias is not clear. The study demonstrates that the inequity was largely unconscious, unthinking, and unintentional.”

Dr. Skelding suggested that much of this bias comes from long-held, preconceived notions. “If you look back to textbooks that describe angina, you see a middle-aged gentleman with a cigar, and that becomes the stereotype of angina and coronary artery disease risk,” she said. “What we have to start realizing is that there needs to be a new face for CAD, and it needs to include both genders. We have to realize that it wasn’t a conscious decision on the part of physicians caring for women who deemed them to be lower risk, but until we address that and find ways to overcome that, it will continue to be an issue.”

A Case of Cost Consciousness?

Dr. Bugiardini noted an additional reason why physicians may be less likely to refer women for cardiac cath—to save costs. “Numerous randomized, controlled trials have confirmed that revascularization is likely to be most beneficial for those ACS patients at highest risk and only marginally beneficial, if at all, for those at lowest risk,” he explained, adding that physicians are under ever-increasing pressure to restrain costs “by limiting invasive procedures to smaller and smaller groups of patients believed to be most likely to benefit.”

The problem with that, Dr. Bugiardini noted, is that women with AMI often present with different symptoms than men.

“We need to start getting away from what’s ‘typical,’” Dr. Skelding said. “Because the typical symptoms in men and women are different. For instance, women tend to have more microvascular disease. We talk about CAD being different in diabetics and nondiabetics, why would we not suppose that CAD would be different between men and women?”


Bugiardini R, Yan AT, Yan RT, et al. Factors influencing underutilization of evidence-based therapies in women. Eur Heart J. 2011;Epub ahead of print.



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Jason R. Kahn, the former News Editor of TCTMD, worked at CRF for 11 years until his death in 2014…

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  • The Canadian ACS II Registry was sponsored by Bristol-Myers Squibb Canada, Canadian Heart Research Centre, Pfizer Canada, and Sanofi-Aventis Canada.
  • Dr. Bugiardini makes no statement regarding conflicts of interest.