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Vol. 72. Issue 8.
Pages 616-624 (August 2019)
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Vol. 72. Issue 8.
Pages 616-624 (August 2019)
Original article
DOI: 10.1016/j.rec.2018.07.010
International Normalized Ratio and Mortality Risk in Acute Heart Failure and Nonvalvular Atrial Fibrillation Patients Receiving Vitamin K Antagonists
Razón internacional normalizada y mortalidad de los pacientes con insuficiencia cardiaca y fibrilación auricular tratados con antagonistas de la vitamina K
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Enrique Santasa, Gema Miñanaa,b, Jana Gummela, Roxana Farcasana, Ana Payáa, Raquel Herediaa, Vicent Bodía,b, Anna Mollara, Vicente Bertomeu-Gonzálezc,d,e, Francisco Javier Chorroa,b,c, Juan Sanchisa,b,c, Josep Lupónc,f,g, Antoni Bayés Genísc,f,g, Julio Núñeza,b,c,
Corresponding author
yulnunez@gmail.com

Corresponding author: Servicio de Cardiología, Hospital Clínico Universitario de Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain.
a Servicio de Cardiología, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
b Departamento de Medicina, Universitat de València, Valencia, Spain
c Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
d Servicio de Cardiología, Hospital Universitario San Juan, San Juan de Alicante, Alicante, Spain
e Departamento de Medicina, Universidad Miguel Hernández, Alicante, Spain
f Servicio de Cardiología, Unidad de Insuficiencia Cardiaca, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
g Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
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Tables (4)
Table 1. Patients’ Baseline Characteristics by INR Category
Table 2. Crude Incidence Rates (per 100 Person-Years) and 95% Confidence Intervals (CIs) for All-Cause and Cause-Specific Mortality by INR Category
Table 3. Risk Estimates (Differences in Mean Survival Times) in the Different Analyses of Primary and Secondary Endpoints in Subtherapeutic (INR < 2) and Supratherapeutic (INR > 3) Categories Compared With INR 2–3
Table 4. Risk Estimates for Different Analyses Meeting the Proportional Hazards Assumption for Subtherapeutic (INR < 2) and Supratherapeutic (INR > 3) Categories Compared With INR 2–3
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Abstract
Introduction and objectives

Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up.

Methods

In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality.

Results

During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years’ follow-up: –0.50; 95%CI, –0.77 to –0.23 years; P < .001; and –0.40; 95%CI, –0.70 to –0.11 years; P = .007, respectively, compared with INR 2-3.

Conclusions

In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.

Keywords:
Atrial fibrillation
International normalized ratio
Heart failure
Abbreviations:
CV
INR
NVAF
RMST
VKA
Resumen
Introducción y objetivos

Los pacientes con insuficiencia cardiaca en tratamiento con antagonistas de la vitamina K (AVK) por fibrilación auricular no valvular (FANV) a menudo presentan valores alterados de la razón internacional normalizada (INR). El objetivo es evaluar la asociación entre la INR al ingreso por insuficiencia cardiaca y el riesgo de mortalidad en el seguimiento.

Métodos

Estudio observacional retrospectivo en el que se evaluó la INR al ingreso de 1.137 pacientes consecutivos con insuficiencia cardiaca aguda en tratamiento con AVK por FANV. Esta se categorizó en: INR en rango óptimo (INR = 2-3, n = 210), infraterapéutica (INR < 2, n = 660) o supraterapéutica (INR > 3, n = 267). La asociación independiente entre INR y mortalidad se evaluó mediante cálculo restringido de las diferencias en tiempos de supervivencia media, dado que la INR no cumple la condición de proporcionalidad de riesgos de mortalidad.

Resultados

Tras una mediana de 2,15 [0,71-4,29] años, fallecieron 495 pacientes (43,5%). En el análisis multivariable, tanto la INR infraterapéutica como la supraterapéutica se asociaron con un mayor riesgo de mortalidad, con unas diferencias en tiempos de supervivencia media a 5 años de –0,50 años (IC95%,–0,77 a –0,23; p < 0,001) y –0,40 años (IC95%, –0,70 a –0,11; p = 0,007) con respecto a los pacientes con INR 2-3.

Conclusiones

La INR fuera de rango óptimo al ingreso de los pacientes con insuficiencia cardiaca aguda en tratamiento con AVK por FANV se asocia de manera independiente con un mayor riesgo de mortalidad en el seguimiento a largo plazo.

Palabras clave:
Fibrilación auricular
Razón internacional normalizada
Insuficiencia cardiaca

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