Comparison of Presentation, Perception, and Six- Month Outcome Between Women and Men >75 Years of Age With Angina Pectoris Gabriela M. Kuster, MD, Peter Buser, MD, Stefan Osswald, MD, Christoph Kaiser, MD, Ronald Scho ¨nenberger, MD, Christian Schindler, PhD, Wolfgang Amann, MD, Peter Rickenbacher, MD, and Matthias Pfisterer, MD, for the Trial of Invasive Versus Medical Therapy in the Elderly (TIME) Investigators L ittle is known about disease presentation, percep- tion, and quality of life (QoL) in elderly women compared with men with chronic coronary artery dis- ease (CAD) and their impact on outcome after medical or invasive treatment. The Trial of Invasive versus Medical therapy in Elderly patients with chronic CAD (TIME) was a prospective randomized study 1 that offered the opportunity to examine these questions in patients 75 years of age. The present analysis ex- amines the relation of CAD presentation and percep- tion to outcome in women compared with men. ••• In a prospective, randomized multicenter Swiss trial, 301 patients aged 75 years with chronic angina of at least Canadian Cardiac Society class II, and despite receiving 2 antianginal drugs, were random- ized to optimized medical therapy or an invasive strat- egy with coronary angiography followed by revascu- larization (percutaneous coronary intervention or cor- onary artery bypass grafting), if feasible. The primary end point was QoL assessed by standardized question- naire and presence and/or absence of major adverse clinical events (MACEs; death of all causes, nonfatal myocardial infarction, or hospitalization for uncon- trolled symptoms and/or acute coronary syndrome with or without need for revascularization). Patients were excluded if they had acute myocardial infarction within the previous 10 days, concomitant valvular or other heart disease, predominant congestive heart fail- ure, or had not provided consent for a possible revas- cularization procedure. Details of the TIME study have been previously reported. 1 After collection of baseline data, QoL was assessed by a self-administred questionnaire containing the SF-36, 2 the Duke Activ- ity Status Index, 3 the Rose angina questionnaire, 4 and questions about education and social status. The study was approved by the ethics committee of the Swiss Academy of Medical Sciences and by the local ethics committees of each of the 14 Swiss Centers. Patients gave written informed consent. The present study represents a prespecified sub- group analysis of the main trial. Women with both treatment assignments were compared with men, and subgroups were formed of both genders with versus without CAD (for the invasive group only, where coronary angiograms were available). Six-month out- come with regard to QoL and MACEs were analyzed for gender and both treatment groups. All analyses were performed on an intention-to- treat basis. Power and statistical analyses are detailed in the report of the TIME 6-month data. 1 Briefly, for comparison of quantitative variables and categoric values, the Wilcoxon-Mann-Whitney test and Fisher’s exact and chi-square tests were used, respectively. Changes in quantitative variables within groups were assessed by paired t and sign-rank tests, and time variables with censored values were described by Kaplan-Meier statistics. To assess gender differences in survival, proportional hazard models with treat- ment-specific baseline hazard functions were used. QoL questionnaires were analyzed according to the specific tests used. The primary end point was ana- lyzed by intention-to-treat as a composite end point, and all components separately as secondary end points. To assess the influence of different predictors on time-to-event variables, Cox proportional hazard models were used. The study population consisted of 301 patients; 44% of whom were women with a mean age of 80 years (range 75 to 89). Baseline characteristics are listed in Table 1. Women were the same age as men, had a similar severity of angina despite receiving antianginal drugs (2.6  0.7 vs 2.4  0.6, p = NS), and a similar incidence of comorbidities. However, women more frequently had a history of hypertension, were less often smokers, had less previous revascu- larizations, and presented more often with accompa- nying dyspnea despite receiving more diuretics and angiotensin-converting enzyme inhibitors. Still, non- invasive left ventricular ejection fraction was higher in women than in men. Coronary angiograms in the invasive group patients showed no significant disease in 15% of women versus 1% of men and overall significantly less extensive vessel disease in women than in men (p 0.001). Revascularization rates as well as stents (86% in angioplasty) or internal mam- mary artery use (83% in bypass surgery) were very similar for women (74%) and men (73%). After ex- clusion of patients without significant CAD, the base- From the University Hospital, Basel; Bu ¨rgerspital Solothurn, Solothurn; The Institute of Social and Preventive Medicine, University Basel, Basel; University Hospital, Zu ¨rich; and Kantonsspital Bruderholz, Brud- erholz, Switzerland. The TIME study was supported by grants from the Swiss Heart Foundation, Berne, and the ADUMED Foundation, Lu- gano, Switzerland. Dr. Pfisterer’s address is: Division of Cardiology, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: pfisterer@email.ch. Manuscript received June 25, 2002; re- vised manuscript received and accepted October 7, 2002. 436 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matter The American Journal of Cardiology Vol. 91 February 15, 2003 doi:10.1016/S0002-9149(02)03240-X