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.