ABSTRACT
TOPCAT was a multinational clinical trial of 3,445 heart failure with preserved ejection fraction (HFpEF) patients that enrolled in 233 sites in six countries in North America, Eastern Europe and South America. Patients with a heart failure hospitalization in the last 12 months or an elevated B-type natriuretic peptide (BNP) were randomized to the mineralocorticoid receptor antagonist spironolactone vs. placebo. Sites in Russia and the Republic of Georgia provided the majority of early enrollment, primarily based on the hospitalization criterion since BNP levels were initially unavailable there. With the emergence of country-specific aggregate event rate data indicating lower rates in Eastern Europe and differences in patient characteristics there, the DSMB recommended relatively increasing enrollment in North America plus other corrective measures. Although final enrollment reflected the increased contribution from North America, a plurality of the final cohort came from Russia and Georgia (49% vs. 43% in North America). BNP measurements from Russia and Georgia available later in the trial suggested no or a mild level of heart failure consistent with low event rates. The primary results showed no significant spironolactone treatment effect overall (primary endpoint hazard ratio 0.89 (0.77, 1.04)), with a significant hazard ratio in North and South America (0.82 (0.69, 0.98), p =0.026) but not in Russia and Georgia (1.10 (0.79, 1.51), interaction p = 0.12). This report describes the DSMB's detection and management recommendations for regional differences in patient characteristics in TOPCAT, and suggests methods of surveillance and corrective actions that may be useful for future trials.
ABSTRACT
OBJECTIVE: To evaluate whether racial and ethnic disparities exist in obstetric care and adverse outcomes. METHODS: We analyzed data from a cohort of women who delivered at 25 hospitals across the United States over a 3-year period. Race and ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, or Asian. Associations between race and ethnicity and severe postpartum hemorrhage, peripartum infection, and severe perineal laceration at spontaneous vaginal delivery as well as between race and ethnicity and obstetric care (eg, episiotomy) relevant to the adverse outcomes were estimated by univariable analysis and multivariable logistic regression. RESULTS: Of 115,502 studied women, 95% were classified by one of the race and ethnicity categories. Non-Hispanic white women were significantly less likely to experience severe postpartum hemorrhage (1.6% non-Hispanic white compared with 3.0% non-Hispanic black compared with 3.1% Hispanic compared with 2.2% Asian) and peripartum infection (4.1% non-Hispanic white compared with 4.9% non-Hispanic black compared with 6.4% Hispanic compared with 6.2% Asian) than others (P<.001 for both). Severe perineal laceration at spontaneous vaginal delivery was significantly more likely in Asian women (2.5% non-Hispanic white compared with 1.2% non-Hispanic black compared with 1.5% Hispanic compared with 5.5% Asian; P<.001). These disparities persisted in multivariable analysis. Many types of obstetric care examined also were significantly different according to race and ethnicity in both univariable and multivariable analysis. There were no significant interactions between race and ethnicity and hospital of delivery. CONCLUSION: Racial and ethnic disparities exist for multiple adverse obstetric outcomes and types of obstetric care and do not appear to be explained by differences in patient characteristics or by delivery hospital. LEVEL OF EVIDENCE: II.