Women Are Less Likely to Get Secondary Prevention Medications and Cardiac Rehabilitation

Note: This is the Part 2 of a two-part "Pro-Con" set. Go to Part 1.

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

Figure 1
Likelihood of receiving evidence-based treatment, as assessed by logistic regression models adjusted for risk factors. Women are compared with men. P values refer to interaction between age category (or type of MI) and sex. Reprinted with permission from Redfors et al.2

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

  1. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017;135:e146-e603.
  2. Redfors B, Angerås O, Råmunddal T, et al. Trends in Gender Differences in Cardiac Care and Outcome After Acute Myocardial Infarction in Western Sweden: A Report From the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). J Am Heart Assoc 2015;4:e001995.
  3. Lund LH, Braunschweig F, Benson L, Ståhlberg M, Dahlström U, Linde C. Association between demographic, organizational, clinical, and socio-economic characteristics and underutilization of cardiac resynchronization therapy: results from the Swedish Heart Failure Registry. Eur J Heart Fail 2017;19:1270-9.
  4. Chatterjee NA, Borgquist R, Chang Y, et al. Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator. Eur Heart J 2017;38:1485-94.
  5. Mehta LS, Beckie TM, DeVon HA, et al. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation 2016;133:916-47.
  6. Anand SS, Xie CC, Mehta S, et al. Differences in the management and prognosis of women and men who suffer from acute coronary syndromes. J Am Coll Cardiol 2005;46:1845-51.
  7. Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 2005;45:832-7.
  8. Bugiardini R, Yan AT, Yan RT, et al. Factors influencing underutilization of evidence-based therapies in women. Eur Heart J 2011;32:1337-44.
  9. Koopman C, Vaartjes I, Heintjes EM, et al. Persisting gender differences and attenuating age differences in cardiovascular drug use for prevention and treatment of coronary heart disease, 1998-2010. Eur Heart J 2013;34:3198-205.
  10. Jørgensen CH, Gislason GH, Ahlehoff O, Andersson C, Torp-Pedersen C, Hansen PR. Use of secondary prevention pharmacotherapy after first myocardial infarction in patients with diabetes mellitus. BMC Cardiovasc Disord 2014;14:4.
  11. Smolina K, Ball L, Humphries KH, Khan N, Morgan SG. Sex Disparities in Post-Acute Myocardial Infarction Pharmacologic Treatment Initiation and Adherence: Problem for Young Women. Circ Cardiovasc Qual Outcomes 2015;8:586-92.
  12. Reuter H, Markhof A, Scholz S, et al. Long-term medication adherence in patients with ST-elevation myocardial infarction and primary percutaneous coronary intervention. Eur J Prev Cardiol 2015;22:890-8.
  13. Gunnell AS, Hung J, Knuiman MW, et al. Secondary preventive medication use in a prevalent population-based cohort of acute coronary syndrome survivors. Cardiovasc Ther 2016;34:423-30.
  14. Eisen A, Cannon CP, Braunwald E, et al. Predictors of Nonuse of a High-Potency Statin After an Acute Coronary Syndrome: Insights From the Stabilization of Plaques Using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) Trial. J Am Heart Assoc 2017;6:e004332.
  15. Rosenson RS, Farkouh ME, Mefford M, et al. Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014. J Am Coll Cardiol 2017;69:2696-706.
  16. Shaw LJ, Bairey Merz CN, Pepine CJ, et al. Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol 2006;47:S4-S20.
  17. Fulcher J, O'Connell R, Voysey M, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015;385:1397-405.
  18. Chakkalakal RJ, Higgins SM, Bernstein LB, et al. Does patient gender impact resident physicians' approach to the cardiac exam? J Gen Intern Med 2013;28:561-6.
  19. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-425.
  20. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:e344-426.
  21. Balady GJ, Williams MA, Ades PA, et al. Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation 2007;115:2675-82.
  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.
  23. Samayoa L, Grace SL, Gravely S, Scott LB, Marzolini S, Colella TJ. Sex differences in cardiac rehabilitation enrollment: a meta-analysis. Can J Cardiol 2014;30:793-800.
  24. Suaya JA, Shepard DS, Normand SL, Ades PA, Prottas J, Stason WB. Use of cardiac rehabilitation by Medicare beneficiaries after myocardial infarction or coronary bypass surgery. Circulation 2007;116:1653-62.
  25. Oosenbrug E, Marinho RP, Zhang J, et al. Sex Differences in Cardiac Rehabilitation Adherence: A Meta-analysis. Can J Cardiol 2016;32:1316-24.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Diet, Hypertension

Keywords: Acute Coronary Syndrome, Female, Risk Factors, Cholesterol, LDL, Angiotensin-Converting Enzyme Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Aspirin, Blood Pressure, Hemoglobin A, Glycosylated, 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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