Cardiovascular disease is the most common cause of death for both sexes.¹ Although cardiac care has improved considerably for both women and men over the past decades, there are several areas in which women have benefited less than men.^2-5

Among patients with acute coronary syndromes (ACS), studies have consistently shown that women are less likely than men to receive guideline-recommended therapies.^2-4,6-15 There are several possible reasons for this, including

1. differences in disease phenotype between women and men,¹⁶
2. uncertainties related to the efficacy or safety of the treatment in women,¹⁷
3. more pronounced side effects in women,¹⁷ and
4. sex bias.¹⁸

Secondary Prevention Medications

Numerous studies have shown that women are less likely than men to receive guideline-recommended secondary prevention medications after suffering an ACS (Table 1). The nationwide Swedish quality registries show that when compared with men, women with acute myocardial infarction (MI) are less likely to receive reperfusion therapy. Women are also less likely to receive beta-blockers, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB), statins, and dual antiplatelet therapy at discharge (Figure 1). In contrast, women are more likely to be prescribed nitrates when discharged (drugs that have a less well-established role in current guidelines). Similarly, a smaller study from Germany showed that among patients with ST-elevation myocardial infarction (STEMI), women were less likely than men to be prescribed beta-blockers at discharge but were more likely to receive calcium channel antagonists (also drugs with a less well-established role in secondary prevention after MI).¹² Underutilization of guideline-recommended therapies in women appears to be particularly pronounced among younger patients and patients with STEMI.^2,9,11 Taken together, the studies in Table 1 provide compelling evidence that women are less likely than men to receive secondary prevention medications after suffering an ACS.

Table 1: Differences Between Women and Men in the Likelihood of Receiving Secondary Prevention After Suffering an ACS

Source	Publication Year	Study Population	Finding
Anand et al.6	2005	Patients with ACS, 1998-2000	Women treated less aggressively than men Less likely to receive beta blocker at discharge
Blomkalns et al.7	2005	Patients with non–ST-segment elevation acute coronary syndromes, 2000-2002	Women less likely to receive secondary prevention Less likely to receive secondary prevention
Bugiardini et al.8	2011	Patients with ACS, 1999-2001	Women less likely to receive secondary prevention Less likely to receive statins and ACEI after multivariate adjustment
Koopman et al.9	2013	Patients with ACS, 1998-2010	Women less likely to receive secondary prevention Particularly younger women
Jorgensen10	2014	Patients with acute MI, 1997-2006	Women less likely to receive secondary prevention Less likely to receive beta-blockers, clopidogrel, and statins
Redfors et al.2	2015	Patients with acute MI, 1995-2014	Women less likely to receive secondary prevention Particularly women with STEMI & younger women No apparent improvement over the study period
Smolina et al.11	2015	Patients with acute MI, 2004-2011	Women less likely to receive secondary prevention Particularly younger women
Reuter et al.12	2015	Patients with STEMI, 2006-2011	Women less likely to receive beta-blockers but more likely to receive calcium channel blockers at discharge
Gunnel et al.13	2016	Patients with ACS, 2008	Women less likely to receive statins
Eisen et al.14	2017	Patients with ACS from 36 countries, 2009-2011	Women less likely to receive statins
Rosenson et al.15	2017	Patients with acute MI, 2011-2014	Women less likely to receive statins

Figure 1: Adjusted Likelihood of Receiving Evidence-Based Treatment

There are several theories for the underlying reasons for this difference. One is that women are less likely to receive secondary prevention medications because MI has traditionally been considered a man's disease.⁵ Some medications may be withheld from women because the medications are perceived to be less efficacious in women than men. As an example, women with MI are less to have obstructive coronary artery disease compared with men.¹⁶ This may lead physicians to withhold therapies that they strongly associate with atheromatous coronary artery disease, such as statins and dual antiplatelet therapy; however, current guidelines for secondary prevention after ACS are based on information from trials that enrolled both men and women. These trials also did not differentiate between patients based on findings on their coronary angiogram.^19,20 Most importantly, these trials have not demonstrated a differential effect in the efficacy of these therapies for women and men. Thus, until we better understand the different disease phenotypes, guideline-recommended therapies after MI should not be withheld from women.

Medications may also be withheld from women due to fear of side effects. For example, it has been suggested that statins cause debilitating myalgia more often in women than in men; however, there is compelling evidence that statin therapy is as effective at reducing serious adverse events in women as it is in men.¹⁷ There is also suggestion that female sex is a risk factor for bleeding complications after MI.^2,19 In fact, current guidelines list female sex as a risk factor for bleeding complications among patients with ACS. However, because current dual antiplatelet regimens have been similarly effective at reducing the risk of adverse events among women as in men in the pivotal multicenter randomized controlled trials, it is recommended that both women and men should receive dual antiplatelet therapy after being hospitalized due to an ACS.^19,20

Cardiac Rehabilitation

Cardiac rehabilitation is a recognized component of modern cardiac care and is given a Class I recommendation by the American Heart Association and American College of Cardiology.²¹ Unfortunately, relatively few patients participate in cardiac rehabilitation, and women are particularly unlikely to participate.^22-24 Recent studies have shown that women are not only less likely to be enrolled in cardiac rehabilitation, but are also less likely to stay in a program once enrolled.^23,25 Because no sex-related contraindications for cardiac rehabilitation exist, this constitutes another area in which efforts need to be devoted to increase utilization among women with heart disease.

Are Things Different Today?

The data reviewed herein were collected from patients who were treated at least several years ago, and even if most of the studies in Table 1 were published within the last few years, many of the patients that contributed data were treated more than a decade ago. Even the most contemporary studies reflect clinical practice as it was a few years back and not necessarily as it is today. With increasing awareness of sex disparities in cardiac care over the past decade, it is possible that the sex-related differences in the prescription of secondary prevention medications and cardiac rehabilitation have improved in recent years. On the other hand, data from the Swedish quality registries imply that sex differences in secondary prevention after MI have increased rather than decreased over the previous decades.² It will be important to continue to track trends in sex-related disparities in secondary prevention after ACS.

Conclusion

In summary, compelling evidence exists that women with ACS are less likely than men to receive secondary prevention and cardiac rehabilitation. Some of these observed discrepancies are likely accounted for by differences between the sexes in disease phenotype and pathophysiology, as well as by differences in the perceived efficacy, safety, and severity of the side effects of these therapies; however, unfortunately, some of the observed discrepancies may be explained by subconscious gender bias.

References

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22. Witt BJ, Jacobsen SJ, Weston SA, et al. Cardiac rehabilitation after myocardial infarction in the community. J Am Coll Cardiol 2004;44:988-96.
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Keywords: Acute Coronary Syndrome, Female, Risk Factors, Cholesterol, LDL, Angiotensin-Converting Enzyme Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Aspirin, Blood Pressure, Glycated Hemoglobin A, Secondary Prevention, Cardiac Rehabilitation, Cardiovascular Diseases, Risk Adjustment, Sex Characteristics, Retrospective Studies, Cost-Benefit Analysis, Myocardial Infarction, Weight Loss, Patient Compliance, Registries, Angioplasty, Hypertension, Coronary Stenosis, Hyperlipidemias, Primary Prevention, Stents, Diabetes Mellitus, Referral and Consultation, Diet

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