Kristian Kragholm1, Sarah A Goldstein1, Qinghong Yang1, Renato D Lopes1, Phillip J Schulte1, Gwen M Bernacki1, Harvey D White1, Kenneth W Mahaffey1, Robert P Giugliano1, Paul W Armstrong1, Robert A Harrington1, Pierluigi Tricoci1, Frans Van de Werf1, John H Alexander1, Karen P Alexander1, L Kristin Newby2. 1. From Duke Clinical Research Institute, Durham, NC (K.K., S.A.G., Q.Y., R.D.L., P.J.S., G.M.B., J.H.A., K.P.A., L.K.N.); Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand (H.D.W.); Department of Medicine, Stanford University, CA (K.W.M., R.A.H.,); Department of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (R.P.G.); Department of Medicine, University of Alberta, Edmonton, Canada (P.W.A.); and Department of Cardiology, University Hospitals Leuven, Belgium (F.V.d.W.). 2. From Duke Clinical Research Institute, Durham, NC (K.K., S.A.G., Q.Y., R.D.L., P.J.S., G.M.B., J.H.A., K.P.A., L.K.N.); Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand (H.D.W.); Department of Medicine, Stanford University, CA (K.W.M., R.A.H.,); Department of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (R.P.G.); Department of Medicine, University of Alberta, Edmonton, Canada (P.W.A.); and Department of Cardiology, University Hospitals Leuven, Belgium (F.V.d.W.). kristin.newby@duke.edu.
Abstract
BACKGROUND: Representation by age ensures appropriate translation of clinical trial results to practice, but, historically, older patients have been underrepresented in clinical trial populations. As the general population has aged, it is unknown whether clinical trial enrollment has changed in parallel. METHODS AND RESULTS: We studied time trends in enrollment, clinical characteristics, treatment, and outcomes by age among 76 141 patients with non-ST-segment-elevation acute coronary syndrome enrolled in 11 phase III clinical trials over 17 years (1994-2010). Overall, 19.7% of patients were ≥75 years; this proportion increased from 16% during 1994 to 1997 to 21% during 1998 to 2001 and 23.2% during 2002 to 2005, but declined to 20.2% in 2006 to 2010. The number of comorbidities increased with successive time periods irrespective of age. There were substantial increases in the use of evidence-based medication in-hospital and at discharge regardless of age. Although predicted 6-month mortality increased slightly over time, observed 6-month mortality declined significantly in all age strata (1994-1997 versus 2006-2010: <65 years: 3.0% versus 1.9%; 65-74 years: 7.5% versus 3.4%; 75-79 years: 13.0% versus 6.5%; 80-84 years: 17.6% versus 8.2%; and ≥85 years: 24.8% versus 12.6%). CONCLUSIONS: The distribution of enrollment by age in phase III non-ST-segment-elevation acute coronary syndrome trials was unchanged over time. Irrespective of age, post-myocardial infarction mortality decreased significantly over time, concurrent with increased evidence-based care and despite increasing comorbidities. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00089895.
BACKGROUND: Representation by age ensures appropriate translation of clinical trial results to practice, but, historically, older patients have been underrepresented in clinical trial populations. As the general population has aged, it is unknown whether clinical trial enrollment has changed in parallel. METHODS AND RESULTS: We studied time trends in enrollment, clinical characteristics, treatment, and outcomes by age among 76 141 patients with non-ST-segment-elevation acute coronary syndrome enrolled in 11 phase III clinical trials over 17 years (1994-2010). Overall, 19.7% of patients were ≥75 years; this proportion increased from 16% during 1994 to 1997 to 21% during 1998 to 2001 and 23.2% during 2002 to 2005, but declined to 20.2% in 2006 to 2010. The number of comorbidities increased with successive time periods irrespective of age. There were substantial increases in the use of evidence-based medication in-hospital and at discharge regardless of age. Although predicted 6-month mortality increased slightly over time, observed 6-month mortality declined significantly in all age strata (1994-1997 versus 2006-2010: <65 years: 3.0% versus 1.9%; 65-74 years: 7.5% versus 3.4%; 75-79 years: 13.0% versus 6.5%; 80-84 years: 17.6% versus 8.2%; and ≥85 years: 24.8% versus 12.6%). CONCLUSIONS: The distribution of enrollment by age in phase III non-ST-segment-elevation acute coronary syndrome trials was unchanged over time. Irrespective of age, post-myocardial infarction mortality decreased significantly over time, concurrent with increased evidence-based care and despite increasing comorbidities. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00089895.
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