Sex-Associated Differences in Clinical Outcomes after Coronary Stenting in Patients with Diabetes Mellitus Gjin Ndrepepa, MD, Julinda Mehilli, MD, Hildegard Bollwein, MD, Ju ¨ rgen Pache, MD, Albert Scho ¨mig, MD, Adnan Kastrati, MD PURPOSE: It has been suggested that the influence of diabetes on cardiovascular mortality is sex dependent. We undertook this study to determine whether there were sex-related differ- ences in 1-year clinical outcomes following coronary artery stenting in diabetic patients. METHODS: The study included 4460 consecutive patients (1084 women) who underwent coronary artery stenting for sta- ble or unstable angina, of whom 970 (22%) had diabetes. Six- month follow-up angiography was performed in 3452 patients (77.4%). The primary endpoint was the combined incidence of major adverse cardiac events (death, myocardial infarction, and target vessel revascularization). RESULTS: Diabetes was associated with a significant increase in the combined incidence of death, myocardial infarction, and target vessel revascularization at 1 year in women; this incidence was greater in diabetic women than in nondiabetic women (26.9% [84/312] vs. 18.9% [146/772]; odds ratio [OR] = 1.5; 95% confidence interval [CI]: 1.2 to 2.0; P = 0.002). The pri- mary endpoint appeared to be similar in men regardless of dia- betes status (24.6% [162/658] with diabetes vs. 23.3% [634/ 2718] without diabetes; OR = 1.07; 95% CI: 0.90 to 1.27; P = 0.43). There was a significant interaction between diabetes and sex in both unadjusted (P = 0.03) and adjusted (P = 0.04) analyses, with diabetes having a greater negative effect in women than in men for major adverse cardiac events after cor- onary stenting. CONCLUSION: In patients who underwent coronary artery stenting, the increased risk of adverse cardiac events associated with diabetes was more pronounced in women than in men. Am J Med. 2004;117:830 – 836. ©2004 by Elsevier Inc. D iabetes is a major risk factor for coronary heart disease. Indeed, similar rates of cardiovascular mortality have been reported in diabetic patients without previous myocardial infarction and in nondia- betic patients with a history of myocardial infarction (1). One study reported that after a decade of follow-up, car- diovascular mortality was reduced by 36% among non- diabetic men and by 27% in nondiabetic women; it was reduced by only 13% in diabetic men and increased by 23% in diabetic women (2). Other studies have also re- ported sex-related differences in the effect of diabetes on the risk of coronary death (3–7). The reasons for these differences are not completely known. Some investiga- tors have suggested that the more adverse cardiovascular risk profile in diabetic women may play a role (8,9), whereas others have suggested that traditional cardiovas- cular risk factors cannot completely account for these sex differences in cardiovascular mortality (10). Diabetic patients represent a large proportion of the patients referred for percutaneous coronary intervention (11–16), and the incidence of restenosis in patients with diabetes after coronary balloon angioplasty has been re- ported to be higher than in patients without diabetes (11– 13). Coronary stenting has been associated with a sub- stantial reduction in the rate of restenosis among diabetic patients as compared with coronary balloon angioplasty (14 –16). However, a large proportion of diabetic patients who undergo stenting still develop angiographic and clin- ical coronary restenosis. It is not known whether sex plays a role in these outcomes. Therefore, we undertook this study to determine whether there were sex-related differ- ences in 1-year clinical outcomes following coronary stenting in diabetic patients. METHODS Patients The study included 4460 consecutive patients (1084 women) who underwent coronary artery stenting for sta- ble or unstable angina between January 1995 and July 2000. Patients who were treated in the setting of acute myocardial infarction were excluded. Diabetes was de- fined as undergoing active treatment with insulin or oral hypoglycemic agents. For patients on dietary treatment alone, documentation of abnormal fasting blood glucose levels or an abnormal glucose tolerance test according to the World Health Organization criteria was required for the diagnosis of diabetes (17). All patients were treated and studied after giving informed consent. The study From Deutsches Herzzentrum (GN, JM, AS, AK) and 1. Medizinische Klinik Rechts der Isar (HB, JP, AS) der Technischen Universita ¨t Mu- nich, Munich, Germany. Requests for reprints should be addressed to Gjin Ndrepepa, MD, Deutsches Herzzentrum, Lazarettstrasse 36, 80636 Mu ¨nchen, Ger- many, or ndrepepa@dhm.mhn.de. Manuscript submitted June 16, 2003, and accepted in revised form February 12, 2004. 830 © 2004 by Elsevier Inc. 0002-9343/04/$–see front matter All rights reserved. doi:10.1016/j.amjmed.2004.02.036