Elsevier

International Journal of Cardiology

Volume 223, 15 November 2016, Pages 604-610
International Journal of Cardiology

Do randomized clinical trial selection criteria reflect levels of risk as observed in a general population of acute myocardial infarction survivors? The PEGASUS trial in the light of the FAST-MI 2005 registry

https://doi.org/10.1016/j.ijcard.2016.08.191Get rights and content

Highlights

  • We investigated the PEGASUS-TIMI 54 trial criteria in a real life post-MI population.

  • Patients were categorized according to criteria used in PEGASUS trial.

  • We used data from a nationwide French registry including 3670 patients (FAST-MI).

  • Enrichment criteria used in PEGAGUS succeed in defining a high-risk population.

  • Age represents the most discriminant factor.

Abstract

Background

Few clinical trials have focused on populations with a history of distant myocardial infarction (MI). The PEGASUS trial assessed the impact of dual antiplatelet therapy in such patients, selected by enrichment criteria of high cardiovascular risk. Whether the PEGASUS population reflects the risk of a broader post-MI population is questionable. We analyzed whether 4-year mortality of a routine-practice population would differ according to the inclusion and exclusion criteria used in PEGASUS.

Methods

FAST-MI is a nationwide French registry recruiting acute MI patients in November 2005; 2490 patients alive and without recurrent MI at one year were classified into three groups: Group 1 (“PEGASUS-like” population; n = 1395; 56%), Group 2 (population having ≥ 1 exclusion criterion for the trial; n = 677; 27%), and group 3 (population meeting neither the PEGASUS inclusion nor exclusion criteria; n = 418, 17%).

Results

Group 1 patients were older than Group 3 patients, with higher GRACE scores, more comorbidity, and less STEMI, but were younger than the PEGASUS trial population. Enrichment criteria successfully defined a population at higher risk: 4-year survival 83% in Group 1, 97% in Group 2, and 68% in Group 3 (P < 0.001). Among risk-enrichment criteria, age alone was highly discriminant: in PEGASUS-like patients, survival was 78% in those ≥ 65 versus 94% in those < 65 years.

Conclusions

Enrichment criteria used in PEGAGUS succeed in defining a population at increased risk in patients with prior MI, age being the most discriminant factor. The trial population, however, was notably younger and more masculine than the corresponding real-life population in France.

Clinicaltrials.govnumber:NCT00673036.

Introduction

Only limited data are available regarding the long-term outcomes of myocardial infarction (MI) patients, past the first months following the acute event [1], [2], [3], [4]. Among contemporary data, the largest real-world surveys and registries have been focused on patients with stable coronary artery disease, who may or may not have a history of MI [5]. Some recent randomized trials have also included patients with long-term follow-up, but none have specifically focused on patients with a relatively recent MI, past the initial period of clinical instability [6], [7], [8].

The PEGASUS-TIMI 54 trial assessed the impact of ticagrelor in aspirin-treated patients at moderate to high risk, one to three years after an acute myocardial infarction (AMI) [9], [10]. Whether the population included in this international trial will actually reflect a similarly selected real-life population remains an open question.

Therefore, the aim of the present study was to assess the proportion of patients meeting the inclusion and exclusion criteria of the PEGASUS trial and to determine whether 5-year mortality of a routine-practice population selected according to the criteria used to select the population in the PEGASUS-TIMI 54 trial, would differ from those of non-selected or excluded patients, using data from the French registry of Acute ST-elevation or non-ST-elevation Myocardial Infarction (FAST-MI) 2005.

Section snippets

FAST-MI 2005 registry

The population and methods of the FAST-MI 2005 registry have been described in detail in previous publications [11], [12]. Briefly, the objective of the study was to collect comprehensive data on the management and outcomes of consecutive patients admitted to intensive care units for definite AMI over a one-month period in France at the end of 2005, irrespective of the type of institution receiving the patients (i.e. university hospitals, public hospitals or private clinics, with or without

Prevalence of the 3 population groups

From an initial population of 3059 patients included in the survey, 2490 were alive at one year and had no recurrent AMI. The PEGASUS-like population (n = 1395) represented 56% of the population of one-year survivors without intercurrent AMI. The non-PEGASUS population without exclusion criteria (n = 677) represented 27% and the patients with at least one exclusion criterion (n = 418) represented 17% of the overall population (Fig. 1).

In line with the selection criteria, the prevalence of the

Discussion

The present data from a large French nationwide registry indicate that the PEGASUS-like population (i.e. patients with enrichment criteria used in the PEGASUS trial) represents 56% of the population of one-year survivors without intercurrent AMI or stroke. This population is associated with a higher risk of major adverse cardiovascular events (including death) compared to the non-PEGASUS population without exclusion criteria. After adjusting for confounders, there was no statistically

Conclusions

In an everyday population of post-MI patients in France in 2005, a population selected by applying the PEGASUS inclusion and exclusion criteria represents over half of the population of one-year survivors without intercurrent AMI or stroke. The population meeting these criteria, however, substantially differs from the population included in the randomized controlled trial. The enrichment criteria used in the PEGAGUS trial succeed in defining a population at increased risk of death and major

Conflict of interest

Dr. Puymirat reported speaker, board membership, and consulting fees: Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Lilly, MSD, Sanofi-aventis, Servier. Dr. Schiele reported receiving grant support to his institution and travel support for scientific meetings: AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Lilly, Medtronic, Pfizer; sanofi aventis, Servier, and Takeda. Dr. Ferrières reported receiving grants and speaker fees: AstraZeneca, Genzyme, Merck, Novartis, and Servier. Dr. Simon

Funding sources

FAST-MI 2005 is registry of the French Society of Cardiology and was supported by unrestricted grants from Pfizer and Servier, and an additional grant from the Caisse Nationale d'Assurance Maladie-Travailleurs Salariés. None of the companies had a role in the design and conduct of the study, data collection and management. They were not involved in the analysis and interpretation of the data, nor in the preparation, review, or approval of the manuscript.

Acknowledgments

The authors are deeply indebted to the patients having agreed to participate in the survey, all physicians having taken care of the patients at the participating and all personnel involved in the registry organization.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [14].

References (14)

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