Under-representation of elderly and women in clinical trials

Published:January 10, 2017DOI:


      • Elderly and women have been often under-represented in randomised clinical trials in heart failure.
      • Elderly have a higher incidence of disease-related morbidities, and adverse drug related events.
      • Women have differ in presentation, clinical manifestations and outcomes in comparison to men.
      • Aim of this review is to analyse how current recommendations for treatments of heart failure are devised for elderly and women.



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


      Taking into account these issues, the aim of this review is to critically analyse the topic of under-representation of elderly and women in cardiovascular RCTs.


      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 CVD pathophysiology, clinical manifestations and outcomes in comparison to their male counterparts. For these reasons, the results of RCTs obtained in younger men cannot be simply translated in elderly and women. Unfortunately, although international guidelines have been published to increase the enrolment of elderly and women, their recruitment is still insufficient. Thus, the inclusion of these subgroups in cardiovascular RCTs is a key aspect to acquire evidence-based knowledge in the understanding and management of CVDs in elderly and women.


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        • Neugarten B.
        Middle Age and Aging.
        The University of Chicago Press, Chicago and London1968
        • Appelman Y.
        • van Rijn B.B.
        • Ten Haaf M.E.
        • Boersma E.
        • Peters S.A.
        Sex differences in cardiovascular risk factors and disease prevention.
        Atherosclerosis. 2015 Jul; 241: 211-218
        • Vitale C.
        • Mendelsohn M.E.
        • Rosano G.M.
        Gender differences in the cardiovascular effect of sex hormones.
        Nat. Rev. Cardiol. 2009; 6: 532-542
        • Healy B.
        The Yentl syndrome.
        N. Engl. J. Med. 1991; 325: 274-276
        • Rosano G.M.
        • 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: 2677-2680
        • Knickman J.R.
        • Snel E.K.
        The 2030 problem: caring for aging baby boomers.
        Health Serv. Res. 2002 Aug; 37: 849-884
        • Mangoni A.A.
        Cardiovascular drug therapy in elderly patients: specific age-related pharmacokinetic, pharmacodynamic and therapeutic considerations.
        Drugs Aging. 2005; 22: 913-941
        • Guyatt G.H.
        • Haynes R.B.
        • Jaeschke R.Z.
        • Cook D.J.
        • Green L.
        • Naylor C.D.
        • 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. Sep 13 2000; 284: 1290-1296
        • 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: 112-121
        • Furberg C.
        To whom do the research findings apply?.
        Heart. 2002; 87: 570-574
        • Tonkin A.M.
        Evaluation of large scale clinical trials and their application to usual practice.
        Heart. 2000; 84: 679-684
        • 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 (iii-iv, ix-x, 1-15)
        • Doyal L.
        Sex, gender, and health: the need for a new approach.
        BMJ. 2001; 323: 1061-1063
        • 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; 20: 514-535
        • Li G.
        • Cheng G.
        • Wu J.
        • Zhou X.
        • Liu P.
        • Sun C.
        Drug-induced long QT syndrome in women.
        Adv. Ther. 2013 Sep; 30: 793-802
        • Maas A.H.
        • van der Schouw Y.T.
        • Regitz-Zagrosek V.
        • Swahn E.
        • Appelman Y.E.
        • 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 Jun; 32: 1362-1368
      1. Lancet. 1994; 344: 1383-1389
        • Azad N.
        • Kathiravelu A.
        • Minoosepeher S.
        • Hebert P.
        • Fergusson D.
        Gender differences in the etiology of heart failure: a systematic review.
        J. Geriatr. Cardiol. Mar 2011; 8: 15-23
        • Rossignol P.
        • Girerd N.
        • Bakris G.
        • Vardeny O.
        • Claggett B.
        • McMurray J.J.V.
        • Swedberg K.
        • Krum H.
        • van Veldhuisen D.J.
        • Shi H.
        • Spanyers S.
        • Vincent J.
        • Fay R.
        • Lamiral Z.
        • Solomon S.D.
        • Zannad F.
        • Pitt B.
        Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia.
        Eur. J. Heart Fail. 20 NOV 2016; (published online:)
        • Cherubini A.
        • Del Signore S.
        • Ouslander J.
        • Semla T.
        • Michel J.
        Fighting against age discrimination in clinical trials.
        J. Am. Geriatr. Soc. 2010; 58: 1791-1796
        • Heiat A.
        • Gross C.P.
        • Krumholz H.M.
        Representation of the elderly, women, and minorities in heart failure clinical trials.
        Arch. Intern. Med. 2002; 162: 1682-1688
        • Valentina Serra V.
        • Watson J.
        • Sinclair D.
        • Kneale D.
        Living Beyond 100: A Reporton Centenarians.
        International Longevity Centre, London2011
        • Butler R.N.
        Age-ism: another form of bigotry.
        Gerontologist. 1969; 9: 243-246
        • Bugental D.B.
        • Hehman J.A.
        Ageism: a review of research and policy implications.
        Soc. Issues Policy Rev. 2007; 1: 173-216
        • Fried L.P.
        • Ferrucci L.
        • Darer J.
        • Williamson J.D.
        • 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: 255-263
        • 4. Centers for Medicare & Medicaid Services
        Chronic Conditions Among Medicare Beneficiaries [Internet].
        ([cited 2012 May 4]. Available from)
        • Bressler R.
        • Bahl J.J.
        Principles of drug therapy for the elderly patient.
        Mayo Clin. Proc. 2003; 78: 1564-1577
        • Turnheim K.
        When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly.
        Exp. Gerontol. 2003; 38: 843-853
        • Nair B.R.
        Evidence based medicine for older people: available, accessible, acceptable, adaptable?.
        Australas. J. Ageing. 2002; 21: 58-60
        • 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; 136: 161-167
        • Rehman H.U.
        Under-representation of the elderly in clinical trials.
        Eur. J. Intern. Med. Oct 2005; 16: 385-386
        • Cerreta F.
        • Eichler H.G.
        • Rasi G.
        Drug policy for an aging population—the European medicines agency's geriatric medicines strategy.
        N. Engl. J. Med. 2012; 367: 1972-1974
        • Authors/Task Force Members
        • Piepoli M.F.
        • Hoes A.W.
        • Agewall S.
        • Albus C.
        • Brotons C.
        • Catapano A.L.
        • et al.
        2016 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. Jun 27 2016;