The conventional reporting of composite endpoints in clinical trials has an inherent limitation in that it emphasizes each patient's first event, which is often the outcome of lesser clinical importance. To overcome this problem, we introduce the concept of the win ratio for reporting composite endpoints. Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. Consider a primary composite endpoint, e.g. cardiovascular (CV) death and heart failure hospitalization (HF hosp) in heart failure trials. For each matched pair, the new treatment patient is labelled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, only then they are labelled a 'winner' or 'loser' depending on who had a HF hosp first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers. A 95% confidence interval and P-value for the win ratio are readily obtained. If formation of matched pairs is impractical then an alternative win ratio can be obtained by comparing all possible unmatched pairs. This method is illustrated by re-analyses of the EMPHASIS-HF, PARTNER B, and CHARM trials. The win ratio is a new method for reporting composite endpoints, which is easy to use and gives appropriate priority to the more clinically important event, e.g. mortality. We encourage its use in future trial reports.

Aims The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. Methods and results We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long‐term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P < 0.0001) and all‐cause mortality (HR 1.19 per 1 SD increase, P < 0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi‐square). Conclusion Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.

Health Technology Assessment programme; National Institute for Health Research, UK.

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