The restricted mean survival time as a replacement for the hazard ratio and the number needed to treat in long‐term studies

AIMS: We applied the restricted mean survival time (RMST) to analyse the survival data reported in the PARADIGM‐HT trial in which sacubitril + valsartan was studied in comparison with enalapril in patients with heart failure. The estimates of this parameter were compared with the published values of hazard ratio (HR). METHODS: Two endpoints were evaluated: a composite of death or hospitalization and cardiovascular death. Our analyses were performed by considering the original follow‐up of 41.4 months and on the basis of a lifetime perspective. All statistical calculations were carried out using specific packages developed under the R‐platform. RESULTS: According to our RMST analysis, the results for the composite endpoint in the comparison of sacubitril + valsartan vs. enalapril showed an improvement from 32.9 to 34.2 months (gain of 1.25 months). This result is based on a time horizon of 41.4 months. The results for the cardiovascular mortality endpoint showed a RMST of 37.2 months for sacubitril + valsartan vs. 36.2 for enalapril (gain of 0.96 months). In the two lifetime analyses, the improvements were much more relevant and yielded a gain of 25.8 months for the composite endpoint and 27.6 months for survival free from cardiovascular death. CONCLUSIONS: Using the data of the PARADIGM‐HT trial, our analysis confirmed that the RMST has documented advantages over the HR, particularly when the clinical study is characterized by a long follow‐up. The number needed to treat (NNT) has a more specific methodological role and cannot be replaced by the RMST.