Response to comments by Plataki and Williams
Sir: We concur with Drs Plataki, Vaporidi and Georgopoulos that if one uses recombinant human activated protein C (rhAPC), to be safe it should be done very selectively in patients with no “contraindications”. Drs Williams, Macias and Rustige are also correct in that one of the major concerns raised during initial evaluation of rhAPC by the advisory committee to the United States Food and Drug Administration was that the risk of hemorrhage with rhAPC would likely increase when it was used in less controlled clinical settings [1]. Unfortunately, since its approval rhAPC has also failed in subsequent trials to show benefit in low-risk adult patients and in pediatric patients [2, 3]. In post-marketing studies rhAPC has also had a significantly different effect (i.e. no benefit) in the subgroup of high-risk adult patients its use was originally recommended for. Whether this is because the agent lacks efficacy or because those who will benefit from it have not been clearly identified is unknown. Regardless, we hold to our editorial’s conclusion that our understanding of the risk to benefit ratio of rhAPC has changed since approval. It is encouraging, though, that questions about the efficacy of rhAPC since that approval—which have only increased with newer data becoming available—may finally be answered by the randomized trial in high-risk patients requested by the European Medicines Agency and now planned by Eli Lilly and Company [4, 5].