Xavier Rossello1,2,3, João Pedro Ferreira4, Francisca Caimari5, Zohra Lamiral4, Abhinav Sharma6, Cyrus Mehta7, George Bakris8, Christopher P Cannon9,10, William B White11, Faiez Zannad12. 1. Cardiology Department, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son Espases, Palma, Spain. 2. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. 3. Facultat de Medicina, Universitat de les Illes Balears (UIB), Palma, Illes Balears, Spain. 4. Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, 54500, Vandoeuvre lès Nancy, France. 5. Endocrinology and Diabetes Department, Hospital Juaneda Miramar, Palma de Mallorca, Spain. 6. Division of Cardiology, McGill University Health Centre, Montreal, QC, Canada. 7. Cytel Corporation, Cambridge, MA, USA. 8. Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago, Chicago, IL, USA. 9. Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. 10. Baim Institute for Clinical Research, Boston, MA, USA. 11. Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA. 12. Centre D'Investigation Clinique-Plurithématique Inserm CIC-P 1433, Inserm U1116, CHRU Nancy hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, 4 Rue du Morvan, 54500, Vandoeuvre lès Nancy, France. f.zannad@chu-nancy.fr.
Abstract
BACKGROUND: Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE). METHODS: Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling. RESULTS: The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04-1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87-1.22 for women; HR = 1.14; 95% CI 0.96-1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13-2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07-1.66) and nominally so in women (HR = 1.23; 95% CI 0.99-1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex. CONCLUSIONS: Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.
BACKGROUND: Women, older patients and non-White ethnic groups experience a substantial proportion of acute coronary syndromes (ACS), although they have been historically underrepresented in ACS randomized clinical trials (RCTs). To assess the influence of sex, age and race on major adverse cardiovascular events (MACE) and on heart failure events, we studied patients with type 2 diabetes in a large post-ACS trial (EXAMINE). METHODS: Differences in baseline characteristics and the respective composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE) and cardiovascular death or heart failure hospitalization (HF events) were evaluated by subgroups in a cohort of post-ACS patients with diabetes, using unadjusted and adjusted Cox regression modelling. RESULTS: The EXAMINE trial enrolled 5380 patients with 35% aged > 65, 32% female and 27% non-White. The risk of MACE was higher in non-White compared to White patients after adjustment for potential confounding (HR = 1.35; 95% CI 1.04-1.75), but there were no significant differences by sex and age (HR = 1.03; 95% CI 0.87-1.22 for women; HR = 1.14; 95% CI 0.96-1.35 for patients ≥ 65 years). The risk of HF events was higher in non-White patients (HR = 1.56; 95% CI 1.13-2.14), and in patients aged > 65 (HR = 1.33; 95% CI 1.07-1.66) and nominally so in women (HR = 1.23; 95% CI 0.99-1.52). The additive risk of each demographic factor (women, older age and non-White race) was greater for HF events in comparison with MACE. Moreover, non-White elderly patients consistently had poorer prognosis regardless of sex. CONCLUSIONS: Older adults, women and non-White patients with diabetes who are post-ACS are often underrepresented in RCTs. The risk for HF events was higher in older and non-White patients, with a trend towards significance in women, whereas only non-White patients (and not women and older patients) were at higher risk for MACE. Future trials should enrich enrollment of these persons at risk.
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