Milton Packer M.D.

Claggett, B., M. Packer, J. J. V. McMurray, K. Swedberg, J. Rouleau, M. R. Zile, P. Jhund, M. Lefkowitz, V. Shi, S. D. Solomon and P.-H. Investigators (2015). “Estimating the Long-Term Treatment Benefits of Sacubitril-Valsartan.” New England Journal of Medicine 373(23): 2289-2290.

Full text of this article.

Although data from clinical trials can be used to estimate the effectiveness of a new therapy as compared with a control during the study follow-up, estimating long-term treatment effects is often difficult. The PARADIGM-HF trial showed that sacubitril–valsartan was superior to enalapril in reducing the rates of death from cardiovascular causes or hospitalization for heart failure (the composite primary end point) and death from any cause among patients with heart failure and a reduced ejection fraction. To estimate the long-term treatment effects of sacubitril–valsartan versus enalapril, we derived actuarial estimates of age-specific event rates and expected survival times using data regarding the age at randomization and the age at the time of an outcome event from the PARADIGM-HF trial (Table S1 and Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). We estimated Kaplan–Meier survival curves for any given age for each treatment group, using age (rather than the time from randomization) as the time scale. We also estimated the average duration of event-free survival according to the area under the survival curve (see the Methods section in the Supplementary Appendix). We then validated our methods by comparing similar long-term survival estimates from the SOLVD-Treatment trial with long-term follow-up data, which showed concordant results (see the Validation of Methods section in the Supplementary Appendix).