Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial

doi:10.1016/S0140-6736(08)61171-X

The Lancet

Volume 372, Issue 9641, 6–12 September 2008, Pages 817-821

https://doi.org/10.1016/S0140-6736(08)61171-X Get rights and content

Summary

Background

The BEAUTIFUL study assessed the morbidity and mortality benefits of the heart rate-lowering agent ivabradine. The placebo arm of the BEAUTIFUL trial was a large cohort of patients with stable coronary artery disease and left-ventricular dysfunction. We did a subanalysis of this placebo group to test the hypothesis that elevated resting heart rate at baseline is a marker for subsequent cardiovascular death and morbidity.

Methods

The association of baseline resting heart rate with cardiovascular outcomes was analysed using Cox proportional hazard models for groups with a heart rate of 70 beats per min (bpm) or greater (2693 patients) versus less than 70 bpm (2745 patients). Additional analyses were done with finer categorisation of heart rate, and with heart rate as a continuous variable.

Findings

After adjustment for baseline characteristics, patients with heart rates of 70 bpm or greater had increased risk for cardiovascular death (34%, p=0·0041), admission to hospital for heart failure (53%, p<0·0001), admission to hospital for myocardial infarction (46%, p=0·0066), and coronary revascularisation (38%, p=0·037). For every increase of 5 bpm, there were increases in cardiovascular death (8%, p=0·0005), admission to hospital for heart failure (16%, p<0·0001), admission to hospital for myocardial infarction (7%, p=0·052), and coronary revascularisation (8%, p=0·034). The analysis of fine-groupings of heart rate suggests that the increase in mortality and heart failure outcomes rises continuously above 70 bpm, whereas the relation is less pronounced for coronary outcomes. For heart failure outcomes, the predictive value of resting heart rate was stronger for earlier events than for later events.

Interpretation

In patients with coronary artery disease and left-ventricular systolic dysfunction, elevated heart rate (70 bpm or greater) identifies those at increased risk of cardiovascular outcomes, with a differential effect on outcomes associated with heart failure and outcomes associated with coronary events.

Funding

Servier, France.

Introduction

Heart rate is increasingly being postulated as a modifiable risk factor for cardiovascular disease. Previous studies have shown a relation between elevated resting heart rate and the risk of cardiovascular disease in the general population¹ and in patients with stable coronary artery disease with or without hypertension.2, 3 However, the threshold at which risk increases in coronary patients, and the quantitative relation between heart rate increase and outcome, are less well defined; data from the Coronary Artery Surgery Study suggested that risk increases around 83 beats per min (bpm) and above,² whereas analysis of the International Verapamil SR/Trandolapril Study indicated increased risk above 75 bpm, well below the conventional definition of tachycardia (>90 bpm).³ There are many hypothetical mechanisms through which elevated heart rate might directly affect cardiovascular risk, mostly related to increased myocardial oxygen demand,⁴ energy depletion,⁵ accelerated atherosclerosis,6, 7, 8, 9 or increased risk of plaque rupture.¹⁰

The placebo arm of the BEAUTIFUL (morBidity-mortality EvAlUaTion of the I_f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction) study11, 12 provided a large population with coronary artery disease and left-ventricular systolic dysfunction, who were well treated in terms of cardiovascular prevention. We tested the hypothesis that elevated resting heart rate at baseline is a marker for subsequent cardiovascular death and morbidity.

Section snippets

Study design and participants

The design and baseline characteristics for the BEAUTIFUL trial have been described previously.11, 12 Briefly, BEAUTIFUL included men and women aged 55 years or older with coronary artery disease, left-ventricular ejection fraction of less than 40%, and end-diastolic short-axis internal dimension larger than 56 mm, identified by echocardiography. The patients were in sinus rhythm and had a resting heart rate of 60 bpm or greater. Resting heart rate was measured at baseline in the supine

Results

The baseline characteristics of the patients enrolled in the placebo group are shown in table 1. Patients with a heart rate of 70 bpm or greater were younger and had a lower left-ventricular ejection fraction and a higher systolic blood pressure than those with a heart rate of less than 70 bpm, and were more likely to have higher NYHA (New York Heart Association) heart failure class, to be smokers or diabetics, and less likely to be treated with β blockers. The mean age of the population was 65

Discussion

In this prospective study, we report an association between elevated heart rate and the risk of cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular dysfunction. Our study confirms previous reports that elevated heart rate is a predictor of mortality and heart failure in patients with coronary artery disease.2, 3 However, our results also extend these observations to coronary events such as admission to hospital for fatal and non-fatal myocardial

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Fast track — ArticlesHeart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

Am Heart J

Am Heart J

J Electrocardiol

J Am Coll Cardiol

Lancet

Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease

Eur Heart J

Fast track — Articles
Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial