Topcat trial trial#
The TOPCAT Trial was funded by the National Institutes of Health, National Heart, Lung, and Blood Institute (contract N01 HC45207). (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial NCT00094302) This report describes the Data Safety and Monitoring Board’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. The primary results showed no significant spironolactone treatment effect overall (primary endpoint hazard ratio : 0.89 95% confidence interval : 0.77 to 1.04), with a significant hazard ratio in North and South America (HR: 0.82 95% CI: 0.69 to 0.98 p = 0.026) but not in Russia and Georgia (HR: 1.10 95% CI: 0.79 to 1.51 interaction p = 0.12).
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B-type natriuretic peptide measurements from Russia and Georgia, available later in the trial, suggested no or a mild level of heart failure consistent with low event rates. Although final enrollment reflected the increased contribution from North America, a plurality of the final cohort came from Russia and Georgia (49% vs.
Topcat trial plus#
With the emergence of country-specific aggregate event rate data indicating lower rates in Eastern Europe and differences in patient characteristics there, the Data Safety and Monitoring Board recommended relatively increasing enrollment in North America plus other corrective measures. Sites in Russia and the Republic of Georgia provided the majority of early enrollment, primarily based on the hospitalization criterion because B-type natriuretic peptide levels were initially unavailable there. Patients with a heart failure hospitalization in the last 12 months or an elevated B-type natriuretic peptide were randomized to the mineralocorticoid receptor antagonist spironolactone versus placebo. Anemia is a significant risk factor for SCD/ACA, death due to presumed CV causes and malignancy in HFpEF.TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) was a multinational clinical trial of 3,445 heart failure with preserved ejection fraction patients that enrolled in 233 sites in 6 countries in North America, Eastern Europe, and South America. In conclusion, patients with HFpEF and anemia are at higher risk of mortality and hospitalization. There was no difference in the risk of myocardial infarction or stroke. Patients with anemia had higher risk of all-cause and HF hospitalizations (HR 1.26 and 1.56, respectively, p<0.05 for both). Among non-CV causes, patients with anemia had higher risk of death due to malignancy (HR 2.61, p<0.05).
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Among CV causes, patients with anemia had higher risk of sudden cardiac death (SCD)/ACA and presumed CV death with no difference in death due to pump failure. These patients were also at higher risk of all-cause and CV mortality with no difference in non-CV mortality. Among 1,748 patients from TOPCAT-Americas, patients with anemia had a 52% higher risk of the primary outcome (hazard ratio 1.52, 95% confidence interval 1.27, 1.83, p<0.05) during a median follow up of 2.4 years. Secondary outcomes were components of the primary outcome, all-cause, CV and non-CV mortality, cause-specific CV and non-CV mortality, all-cause and HF hospitalization, myocardial infarction, and stroke. The primary outcome was a composite of CV mortality, aborted cardiac arrest (ACA), and heart failure (HF) hospitalization. Anemia was defined as hemoglobin of <12 g/dl in females and <13 g/dl in males. In this post-hoc analysis of the TOPCAT trial, we evaluated the prognostic role of anemia in adverse cardiovascular (CV) outcomes in heart failure with a preserved ejection fraction (HFpEF).