To the Editor:

We have read with great interest the general results of the MASCARA study1 and the accompanying editorial2 both recently published in the Revista Española de Cardiología.

The MASCARA study defined itself as a study of effectiveness,3 and not of efficacy, within the management of acute coronary syndrome (ACS) in Spain in 2004-2005. Although the determination of the real benefit of primary percutaneous coronary intervention in ST-elevation acute coronary syndrome and an early invasive strategy in the first 48 hours of non-ST-elevation acute coronary syndrome were among the objectives, this proved impossible to achieve when analyzing the results of the study,1 although the authors note in the conclusions that there has been an increase in invasive strategies in Spain compared to previous studies.

Although the "theoretical" aims of the MASCARA study were not fulfilled, the results presented, in our opinion, are very interesting from the scientific standpoint and contribute interesting reflections on cardiological practice in a time of ever-changing information. Although the differences between randomized studies and registries are well known2 to all the professionals involved in the treatment of ACS patients, we would like to see, in registries as well designed as this, that the outcomes of strategies with clear scientific support—primary percutaneous coronary intervention and early intervention— produce clear clinical improvement "in the real world" as have other recent interventions, such as the use of beta-blockers in heart failure.4

The conclusions of the MASCARA study refer to factors related to the healthcare process that impede the implementation of strategies that have clearly demonstrated benefit in cardiovascular medicine. We should investigate this field further, and analyze the causes of discrepancies between clinical trials and the "real world"—where many of the problems that prevent us providing our patients with better treatment are located—in order to reduce the leading cause of death in our society, cardiovascular disease. These various related factors, some known and others unknown, are the confounding factors that prevent us from transforming efficacy into effectiveness. There is a striking lack of studies on various prevalent diseases, such as the MASCARA study, that report the actual situation regarding these diseases in "the real world."

There are economic reasons for the lack of resources from the public and private sectors which are naturally more interested in demonstrating prognostic improvement, albeit marginal, and in groups scarcely representative of daily clinical practice. Similarly, we also do not know if the benefits of various pharmacological therapies overlap with others, are complementary or only benefit various risk groups (concomitant use of anti-IIb/IIIa, early and dual antiplatelet therapy at various doses for the management of non-ST-elevation acute coronary syndrome), or if, on the other hand, they could cause adverse effects unacceptable in "the real world" (for example, bleeding or hyperkalemia). Health infrastructures can make it unviable to apply various treatments (for example, due to the ambulance system in specific geographic areas).

However, many problems arise in the scientific literature regarding the identification of these associated clinical factors, that is, the factors that confound efficacy with effectiveness. Today, the available scientific information in many cases emphasizes statistically significant differences, although small, obtained from combined outcome variables of debatable clinical relevance. This is done even by analyzing substudies—with their known methodological biases5—of major clinical trials of cardiovascular therapy. Furthermore, scientific meetings and congresses also focus on therapies that show marginal benefits in groups of highly selected patients that scarcely reflect daily clinical reality.

In short, the striking data reported by the MASCARA study once again highlights the relevance of clinical factors related to patient management, that is, the factors confounding efficacy with effectiveness. We should increase our knowledge concerning these factors in order to be able to control them and make efficacy a synonym of effectiveness.