Subgroup analyses of major randomized clinical trials in heart failure are published frequently, but their impact on medical knowledge and practice guidelines has not been previously reported. In a novel analysis, we determined number of citations, impact factors, number of authors, and citations in guidelines of both parent trials and sub-studies; we also qualitatively assessed whether the analyses were described as post-hoc and non-pre-specified. A total of 229 sub-studies evaluating outcomes in patient subgroups were published (median 6, range 0-36 per trial). The number of subjects in the parent trials positively correlated with number of sub-studies (rho = 0.51, P = 0.009). The subgroups are frequently not pre-specified. The impact factors of sub-studies were lower in comparison to the parent trials as were the number of citations two years after the publication date; in addition, parent trials were cited more frequently in European and American professional guidelines compared with the sub-studies. We maintain that the sub-studies derived from major heart failure trials are frequently published, but their contribution to clinical guidelines and medical knowledge are highly debatable.
Keywords: Heart failure; Randomized clinical trials; Sub‐studies.