Skip to main content
SpringerLink
Log in

Are elderly and women under-represented in cardiovascular clinical trials? Implication for treatment

  • geriatrics: at crossroads of medicine
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Elderly and women have been often under-represented in randomised clinical trials testing the effect of treatments on cardiovascular diseases even though these diseases highly affect both of them.

Compared to their younger counterparts elderly have a higher incidence of disease-related morbidities, take more medicines and account for more adverse drug-related events. Similarly women present several differences in pathophysiology, clinical manifestations and outcomes in comparison to their male counterparts. For these reasons the results of randomised clinical trials obtained in younger men cannot be simply translated in elderly and women and the conduction of research and clinical trials in these patient populations is a key aspect to acquire evidence-based knowledge in the understanding and management of their conditions and treatment.

Although the under-representation of elderly and women has been discussed for several years and several international guidelines or recommendation have been published to suggest how to improve the recruitment of these two populations, their recruitment is still insufficient. In particular, frail elderly and those with co-morbidities are not included questioning the external validity and the safety of most treatments.

Aim of this review is to critically analyse how current recommendations for treatments of cardiovascular disease are not adequately devised for elderly and women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes

  1. Centers for Medicare & Medicaid Services: Chronic conditions among Medicare Beneficiaries. 2011 [cited 2012 May 4]. Available from https://www.cms.gov/TheChartSeries/Downloads/ ChartbookFinal.pdf.

References

  1. Neugarten B. Middle age and aging. Chicago and London: The University of Chicago Press; 1968.

    Google Scholar 

  2. Appelman Y, van Rijn BB, Ten Haaf ME, Boersma E, Peters SA. Sex differences in cardiovascular risk factors and disease prevention. Atherosclerosis. 2015;241(1):211–8.

    Article  CAS  PubMed  Google Scholar 

  3. Vitale C, Mendelsohn ME, Rosano GM. Gender differences in the cardiovascular effect of sex hormones. Nat Rev Cardiol. 2009;6(8):532–42.

    Article  CAS  PubMed  Google Scholar 

  4. Healy B. The Yentl syndrome. N Engl J Med. 1991;325(4):274–6.

    Article  CAS  PubMed  Google Scholar 

  5. Rosano GM, Lewis B, Agewall S, Wassmann S, Vitale C, Schmidt H, et al. Gender differences in the effect of cardiovascular drugs: a position document of the Working Group on Pharmacology and Drug Therapy of the ESC. Eur Heart J. 2015;36(40):2677–80.

    Article  PubMed  Google Scholar 

  6. Knickman JR, Snel EK. The 2030 problem: caring for aging baby boomers. Health Serv Res. 2002;37(4):849–84.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mangoni AA. Cardiovascular drug therapy in elderly patients: specific age-related pharmacokinetic, pharmacodynamic and therapeutic considerations. Drugs Aging. 2005;22(11):913–41.

    Article  CAS  PubMed  Google Scholar 

  8. Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, et al. Users’ Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users’ Guides to patient care. Evidence-Based Medicine Working Group. JAMA. 2000;284(10):1290–6.

    Article  CAS  PubMed  Google Scholar 

  9. Britton A, McKee M, Black N, McPherson K, Sanderson C, Bain C. Threats to applicability of randomised trials: exclusions and selective participation. J Health Serv Res Policy. 1999;4(2):112–21.

    CAS  PubMed  Google Scholar 

  10. Furberg C. To whom do the research findings apply? Heart. 2002;87(6):570–4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tonkin AM. Evaluation of large scale clinical trials and their application to usual practice. Heart. 2000;84(6):679–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, Dieppe P. The causes and effects of socio-demographic exclusions from clinical trials. Health Technol Assess. 2005;9(38):iii.

    Article  CAS  PubMed  Google Scholar 

  13. Doyal L. Sex, gender, and health: the need for a new approach. BMJ. 2001;323(7320):1061–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Franconi F, Rosano G, Campesi I. Need for gender-specific pre-analytical testing: the dark side of the moon in laboratory testing. Int J Cardiol. 2015;179:514–35.

    Article  PubMed  Google Scholar 

  15. Li G, Cheng G, Wu J, Zhou X, Liu P, Sun C. Drug-induced long QT syndrome in women. Adv Ther. 2013;30(9):793–802.

    Article  CAS  PubMed  Google Scholar 

  16. Sedlak T, Shufelt C, Iribarren C, Merz CN. Sex hormones and the QT interval: a review. J Womens Health (Larchmt). 2012;21(9):933–41.

    Article  Google Scholar 

  17. Maas AH, van der Schouw YT, Regitz-Zagrosek V, Swahn E, Appelman YE, Pasterkamp G, et al. Red alert for women’s heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010. Eur Heart J. 2011;32(11):1362–8.

    Article  PubMed  Google Scholar 

  18. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.

    Google Scholar 

  19. Azad N, Kathiravelu A, Minoosepeher S, Hebert P, Fergusson D. Gender differences in the etiology of heart failure: A systematic review. J Geriatr Cardiol. 2011;8(1):15–23.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hsich EM, Pina IL. Heart failure in women: a need for prospective data. J Am Coll Cardiol. 2009;54(6):491–8.

    Article  PubMed  Google Scholar 

  21. Cherubini A, Del Signore S, Ouslander J, Semla T, Michel J. Fighting against age discrimination in clinical trials. J Am Geriatr Soc. 2010;58(9):1791–6.

    Article  PubMed  Google Scholar 

  22. Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med. 2002;162(15):1682–8.

    Article  PubMed  Google Scholar 

  23. Serra V, Watson J, Sinclair D, Kneale D. Living beyond 100: a report on centenarians. London: International Longevity Centre; 2011.

    Google Scholar 

  24. Butler RN. Age-ism: another form of bigotry. Gerontologist. 1969;9(4):243–6.

    Article  CAS  PubMed  Google Scholar 

  25. Bugental DB, Hehman JA. Ageism: a review of research and policy implications. Soc Issues Policy Rev. 2007;1(1):173–216.

    Article  Google Scholar 

  26. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improbe targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63.

    Article  PubMed  Google Scholar 

  27. Möller-Leimkühler AM. Gender differences in cardiovascular disease and comorbid depression. Dialogues Clin Neurosci. 2007;9(1):71–83.

    PubMed  PubMed Central  Google Scholar 

  28. Bressler R, Bahl JJ. Principles of drug therapy for the elderly patient. Mayo Clin Proc. 2003;78(12):1564–77.

    Article  CAS  PubMed  Google Scholar 

  29. Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol. 2003;38(8):843–53.

    Article  CAS  PubMed  Google Scholar 

  30. Nair BR. Evidence based medicine for older people: available, accessible, acceptable, adaptable? Aust J Ageing. 2002;21:58–60.

    Article  Google Scholar 

  31. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;2(136):161–7.

    Article  Google Scholar 

  32. Rehman HU. Under-representation of the elderly in clinical trials. Eur J Intern Med. 2005;16(6):385–6.

    Article  CAS  PubMed  Google Scholar 

  33. Cerreta F, Eichler HG, Rasi G. Drug policy for an aging population – the European Medicines Agency’s geriatric medicines strategy. N Engl J Med. 2012;367(21):1972–4.

    Article  CAS  PubMed  Google Scholar 

  34. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016. doi:10.1177/2047487316653709.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Sciences, IRCCS San Raffaele Pisana, via della Pisana, 235, 00163, Rome, Italy

    Cristiana Vitale MD, PhD & Massimo Fini MD

  2. Department of Cardiovascular and Cell Science Research, St. Georges Hospital, London, UK

    Giuseppe Rosano MD, PhD, FACC

Authors
  1. Cristiana Vitale MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Rosano MD, PhD, FACC
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Massimo Fini MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cristiana Vitale MD, PhD.

Ethics declarations

Conflict of interest

C. Vitale, G. Rosano, and M. Fini declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vitale, C., Rosano, G. & Fini, M. Are elderly and women under-represented in cardiovascular clinical trials? Implication for treatment. Wien Klin Wochenschr 128 (Suppl 7), 433–438 (2016). https://doi.org/10.1007/s00508-016-1082-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-016-1082-x

Keywords

Search

Navigation