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Prognostic association of medication trajectories with 3-year mortality in heart failure and preserved ejection fraction: findings from the EPICAL2 cohort study

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aims of this study were to describe combinations of beta-blockers (BB), renin-angiotensin system (RAS) blockers, and mineralocorticoid receptor antagonist (MRA) prescriptions and their trajectories in heart failure with preserved ejection fraction (HFpEF) patients, and to assess their effect on the three-year all-cause and cardiovascular (CV)-mortality.

Methods

We used data from the EPICAL2 cohort of 689 hospitalized HFpEF patients. Medication prescriptions were collected at hospital discharge and at 6, 12, and 24 months after discharge. A multi-trajectory approach was used to conjointly model groups of individuals following similar trajectories over medications prescriptions. We used Cox and Fine‐Gray models, to evaluate respectively the associations between 3-year all‐cause mortality and CV-mortality and the trajectory groups.

Results

Multi-trajectory modelling revealed five distinct trajectory groups: group1 (N = 232, 33.6%) stable ACEI/ARB and BB prescriptions, group 2 (N = 199, 28.8%) stable ACEI/ARB prescription, group 3 (N = 133, 19.3%) stable BB prescriptions, group 4 (N = 78, 11.3%) stable prescriptions of none of the medications, and group 5 (N = 47, 6.8%) stable ACEI/ARB, BB, and MRA prescriptions. As compared to the group 4 of patients receiving none of the three medications, patients receiving a stable prescription of one or a combination of two or the three medications over 2 years) had a lower overall mortality over 3-year follow-up, i.e., group 1 (HR = 0.5, 95% CI 0.4–0.8), group 2 (HR = 0.6, 95% CI:0.4–0.8), group 3 (HR = 0.5, 95% CI:0.4–0.7), and group 5 (HR = 0.5, 95% CI:0.3–0.9). However, none of these trajectory groups was associated with a lower CV-mortality over 3 years.

Conclusion

In an unselected population-based sample of HFpEF patients, the long-term stable use of the combination ACEI/ARB and BB, BB exclusively, ACEI/ARB exclusively, or the combination ACEI/ARB and BB and MRAs was associated with reduced three-year all-cause mortality.

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Availability of data and material

Data archiving is not mandated but data will be made available on reasonable request.

Abbreviations

ACEI:

Angiotensin-converting enzyme inhibitor

ARB:

Angiotensin II receptor blockers

BB:

Beta-blockers

BIC:

Bayesian information criterion

BMI:

Body mass index

COPD:

Chronic obstructive pulmonary disease

CKD:

Chronic kidney disease

CV:

Cardiovascular

EPICAL2:

Epidemiologie et Pronostic de l’Insuffisance Cardiaque Aigue en Lorraine

GBTM:

Group-based trajectory modelling

HFpEF:

Heart failure with preserved ejection fraction

HFrEF:

Heart failure and reduced ejection fraction

MAR:

Missing at random

MCAR:

Missing completely at random

MRAs:

Mineralocorticoid receptor antagonists

NYHA:

New York Heart Association

RAS:

Renin-angiotensin system

RCT:

Randomized controlled trials

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Acknowledgements

The authors thank all physicians from the 21 participating centers in the EPICAL2 clinical cohort study (Hôpitaux de Brabois et Hôpital Central, CHU Nancy; CH Luneville; Espace chirurgical Ambroise Paré Nancy; CH Alpha Santé Mont-Saint-Martin; CH Pont-à-Mousson; CH Saint-Nicolas Verdun; Hôpital Bon-Secours CHR Metz; CH Freyming Merlebach; Hôpital Sainte-Blandine Metz; Hôpital Bel Air CHR Thionville; CH Marie-Madeleine Forbach; Hôpital Alpha Santé Hayange; CH Saint-Nicolas Sarrebourg; Hôpital Lemire SaintAvold; Hôpital des Armées Legouest Metz; Clinique Claude Bernard Metz; CH Saint-Charles Saint-Dié; CH Jean Monnet Epinal; CH Neufchateau; CH Vittel). We would also like to thank all participants and patients of EPICAL2.

Funding

The EPICAL2 cohort study was funded as part of the 2009 National Hospital Program of Clinical Research (PHRC 2009) of the French Ministry of Health and by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHUS-0004).

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Authors and Affiliations

  1. APEMAC, Université de Lorraine, 54000, Nancy, France

    Sarah Bitar & Nelly Agrinier

  2. CHRU-Nancy, INSERM, Université de Lorraine, CIC, Epidémiologie Clinique, 54000, Nancy, France

    Sarah Bitar, Nathalie Thilly & Nelly Agrinier

  3. Département Méthodologie Promotion Investigation, CHRU-Nancy, Université de Lorraine, 54000, Nancy, France

    Nathalie Thilly

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  1. Sarah Bitar
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Contributions

Nelly Agrinier, and Nathalie Thilly contributed to conception and design of the study, data acquisition and interpretation of results, and critically revised the manuscript; Sarah Bitar contributed to analysis and interpretation, and drafted manuscript. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

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Correspondence to Sarah Bitar.

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Bitar, S., Thilly, N. & Agrinier, N. Prognostic association of medication trajectories with 3-year mortality in heart failure and preserved ejection fraction: findings from the EPICAL2 cohort study. Eur J Clin Pharmacol 77, 1569–1581 (2021). https://doi.org/10.1007/s00228-021-03153-6

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