We appreciate the comments by Lozano et al.1 on the consensus document and editorial published in the Revista Española de Cardiología about the use of the polypill.2 This consensus document made some recommendations based on current evidence and, when no evidence was available, the consensus opinion of the authors. As a possible use of the polypill, the consensus mentions patients with a recent coronary event who, given their characteristics, may have a low adherence to therapy. Lozano et al.1 question basic aspects of clinical use of the polypill: bioequivalence of acetylsalicylic acid and the results with this new therapeutic strategy after thrombosis in patients with recent coronary stent placement, particularly, when a new drug-eluting stent was used. Despite the difficulties in establishing causality due to multiple factors that could be related to drug-eluting or bare-metal stent thrombosis, we think the following considerations should be taken into account.
A test formulation is considered bioequivalent to a reference medication if the 90% confidence interval (CI) of the geometric mean for the area under the curve (AUC) and maximum plasma concentration (Cmax) is between 80% and 125%. In the case of the polypill approved in Spain, a bioequivelence trial was conducted. The 90% CI of the geometric means for both AUC and Cmax were within these limits and so bioequivalence was demonstrated according to the accepted criterion. Specifically, in the case of acetylsalicylic acid, the 90% CIs were 96.92%-104.47% for AUC and 84.51%-95.78% for Cmax.3
These results, which demonstrate bioequivalence for acetylsalicylic acid in the polypill compared to separate pills, suggest the polypill can be used in the same indications as acetylsalicylic acid, in this case, as a strategy for secondary prevention in patients with ischemic heart disease, regardless of the clinical presentation (after acute coronary syndrome or in chronic phase) and treatment (after percutaneous revascularization or surgery or in patients without revascularization). In different clinical trials with polypills in patients with ischemic heart disease, which include the FOCUS study,4 there was no evidence of increased ischemic complications compared with the separate components, although that study excluded patients with drug-releasing stents. These patients were, however, included in the SECURE (Secondary Prevention of Cardiovascular Disease in the Elderly Trial, NCT 02596126) study that randomized patients over 65 years of age with recent myocardial infarction to the polypill or the individual components.
CONFLICTS OF INTERESTJ.R. Gonzalez-Juanatey is a speaker for Ferrer International.