Safety of regadenoson in patients with end-stage liver disease

doi:10.1007/s12350-010-9288-1

Journal of Nuclear Cardiology

Volume 18, Issue 1, February 2011, Pages 90-95

https://doi.org/10.1007/s12350-010-9288-1 Get rights and content

Abstract

Background

Regadenoson is a selective A_2A receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined.

Methods and Results

We studied 168 consecutive patients with ESLD who had regadenoson stress gated single photon emission computed tomography MPI between January 2008 and March 2010 before planned orthotopic liver transplantation and compared the hemodynamic responses and safety profile to 168 control patients. There were 72 women (43%) in ESLD versus 87 (52%) in the control group (P= .1). The patients with ESLD were younger (58 ± 7 vs 62 ± 12 years, P= .0002), but more likely to be Caucasians (P= .002). The MPI images were normal in 161 patients (96%) in each group. The left ventricular ejection fraction was 72 ± 10% in ESLD and 66 ± 11% in the control patients (P= .0001). The heart rate increase in response to regadenoson was lower in patients with ESLD than in the control group (16 ± 11 vs 23 ± 16 bpm, P= .0001), but the changes in systolic and diastolic blood pressures were similar (−9 ± 12 vs −11 ± 14 mmHg and −6 ± 8 vs −7 ± 10 mmHg, respectively, P= NS). There were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study.

Conclusion

This is the first study to document the tolerability and safety profile of regadenoson in patients with ESLD.

Introduction

Myocardial perfusion imaging (MPI) is widely used for the detection of coronary artery disease (CAD), risk stratification, and pre-operative evaluation. Approximately half of the studies are performed with a vasodilator stress agent.¹ This is particularly true in patients with end-stage liver disease (ESLD) undergoing liver transplant evaluation as these patients have limited exercise capacity. Orthotopic liver transplantation is the last hope of treatment in patients with ESLD. The number of these procedures continues to increase and the results continue to improve.² The procedure is costly and the resources are limited and hence pre-operative screening to identify high-risk patients is often done.³ Regadenoson, unlike adenosine, is given as a fixed dose. Another relevant pharmacokinetic property of regadenoson is that it is not metabolized and predominately excreted by the kidney (55-60%), while the remaining 40% is excreted by the liver through the bile, also unchanged.⁴ There are no safety data of the drug in patients with ESLD. The purpose of this study is to examine the hemodynamic changes, safety, and tolerability of regadenoson in patients with ESLD.

Section snippets

Patient Selection

We identified from our database, 168 consecutive patients with ESLD who had regadenoson stress gated MPI for clinical indications from 2008 to 2010. The MPI was done before anticipated orthotopic liver transplantation. Since the majority of the patients had normal perfusion images,³^,⁵ we selected a control group of patients with no liver disease (N = 168), from the same time period, and with comparable MPI results. The patients’ records were reviewed for demographics, co-morbidities,

Results

The baseline characteristics of the patients are listed in Table 1. The ESLD group was younger than the control group and included more Caucasians, and fewer patients with hypertension or peripheral vascular disease. The most common causes fro liver transplant were: hepatitis C (40%), non-alcoholic steatohepatitis (18%), alcohol (12%), crypotogenic (11%), primary biliary cirrhosis (6%), and alpha-1 antitrypsin deficiency (4%). Both the groups had a similar proportion of patients with diabetes

Discussion

This is the first study that documents the safety of regadenoson in patients with ESLD. Further, the changes in BP were comparable to those in the control group but the HR response was less. Blunted HR response to adenosine and regadenoson has been described by our group in patients with diabetes, metabolic syndrome, and end-stage renal disease.¹²^,¹³

Most patients undergoing stress MPI for liver transplant evaluation have normal myocardial perfusion, which led some to question the benefit of

Disclosures

Dr Ami E. Iskandrian is an investigator and a consultant to Gilead Sciences, Inc. The other authors have no disclosures.

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El regadenosón es un agonista selectivo para los receptores adenosínicos-2A recién aprobado para inducir estrés farmacológico con una sola inyección en bolo para la adquisición de imágenes SPECT de perfusión miocárdica (IPM).
Se incluyeron 123 pacientes sucesivos referidos para IPM por sospecha de enfermedad arterial coronaria (EAC). A 66 pacientes se les hizo una prueba de estrés con regadenosón y a 57 con adenosina, ambas seguidas por SPECT de manera estándar. A los técnicos, médicos y los pacientes mismos se les pidió que reportaran sus experiencias mediante cuestionarios.
En comparación con la adenosina, el regadenosón no produjo ningún bloqueo auriculoventricular (frente al 10% tras adenosina), pero produjo una taquicardia menor y cambios de la presión arterial pequeños. Todos los síntomas tras el regadenosón fueron más leves y de duración más corta. Hubo menos pacientes que tenían síntomas graves tras el regadenosón (17% vs. 32%, p < 0,01). El efecto secundario reportado más frecuentemente fue la disnea, seguido por rubefacción y angina, pero todos estos efectos se resolvieron rápidamente. La puntuación global de los síntomas, que incluye tanto la severidad como la duración, fue significativamente más baja después del regadenosón que después de la adenosina (6,7 ± 6,3 vs. 10,0 ± 7,9, respectivamente, p < 0,01). Las imágenes SPECT fueron similares. El procedimiento con el regadenosón fue más rápido y práctico.
El regadenosón es un nuevo agente de estrés conveniente para IPM con un perfil muy favorable para los pacientes y los departamentos de cardiología nuclear.
Regadenoson is a recently approved selective adenosine-2A receptor agonist to induce pharmacological stress in myocardial perfusion imaging (MPI) procedures using a single bolus injection.
We included 123 patients referred for MPI because of suspected coronary arterial disease (CAD). Of these, 66 patients underwent a regadenoson stress test and 57 patients underwent an adenosine stress test preceding standard myocardial SPECT imaging. Technicians, physicians and patients were asked to report their experience using questionnaires.
As compared to adenosine, regadenoson did not produce any atrio-ventricular block (0 vs. 10% with adenosine), but did produce minor tachycardia and minimal blood pressure changes while all other side effects were milder and shorter. There were fewer patients with severe complaints after taking regadenoson than adenosine (17% vs. 32%, respectively, p < 0.01). The most frequent complaint reported was dyspnea, followed by flushing and chest pain. However, when they did occur, they usually disappeared rapidly. The overall symptom score, including severity and duration of side effects, was significantly lower after regadenoson than after adenosine (6.7 ± 6.3 vs. 10.0 ± 7.9, respectively; p < 0.01.) SPECT imaging results were similar. The regadenoson procedure was faster and more practical.
Regadenoson, the new selective adenosine-2A receptor agonist, is a stress agent for MPI with a patient- and department friendly profile.
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Citation Excerpt :
Aminophylline, a non-specific adenosine receptor antagonist, may interfere with the vasodilatory activity of regadenoson and can be given intravenously to attenuate adverse reactions. Susceptibility factors Liver disease In 168 patients with end-stage liver disease, who had regadenoson stress-gated single photon emission CT before planned orthotopic liver transplantation and 168 controls, the heart rate increase in response to regadenoson was less in the patients, but the changes in systolic and diastolic blood pressures were similar; there were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study [46C]. Lung disease In a retrospective study of 228 patients with COPD (n = 126) or asthma (n = 102) undergoing SPECT imaging with regadenoson, compared with 1142 patients without COPD or asthma, there were no cases of exacerbation of COPD or asthma after regadenoson [47C].
The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the 2011 publications on adverse reactions to positive inotropic drugs and drugs used in dysrhythmias covers cardiac glycosides, milrinone, the adenosine receptor agonist regadenoson, ajmaline, amiodarone, bepridil, disopyramide, dofetilide, dronedarone, flecainide, mexiletine, and propafenone.
Pharmacologic manipulation of coronary vascular physiology for the evaluation of coronary artery disease
2013, Pharmacology and Therapeutics
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Although regadenoson clearance varies significantly with renal function (Gordi et al., 2007), several prospective studies support the use of regadenoson without dose adjustment in all stages of renal dysfunction (Ananthasubramaniam et al., 2012; Doukky et al., 2012b, 2013). The safety of regadenoson in patients with severe hepatic disease has also been evaluated favorably (Aljaroudi et al., 2011). This flexibility is likely due to the balanced renal and hepatic clearance of regadenoson in subjects with normal renal and liver function.
During the last forty years tremendous progress has been made in our understanding of coronary atherosclerosis and in the development of methods to characterize atherosclerotic disease burden and risk. Stress testing is designed to elucidate abnormalities in myocardial perfusion during stress due to abnormal coronary vasomotor response. We summarize the underlying determinants of normal coronary vasomotor tone as well as its responsiveness to both exercise and pharmacologic stressors. We introduce the various methods of assessing the presence of myocardial ischemia. A detailed discussion of the most commonly used stress agents as well as their clinical advantages and limitations follows.
Regadenoson: A focused update
2013, Journal of Nuclear Cardiology
Since its approval by the Food and Drug Administration in 2008, regadenoson has become the most commonly used vasodilator in the United States. Previous reviews have summarized the pre-clinical and clinical data on the use of regadenoson for myocardial perfusion imaging (MPI). Since then, data have emerged on the safety of this agent in special groups of patients such as those with chronic kidney disease, airway disease (asthma and chronic obstructive pulmonary disease), and liver disease. There has also been recent interest in the use of regadenoson in hybrid protocols with exercise as a way to improve patient tolerance and image quality. Finally, although regadenoson was approved for clinical use based on the agreement rate of regadenoson MPI and adenosine MPI with regards to perfusion abnormalities, data are now available on the prognostic data derived from regadenoson MPI. We will briefly summarize these recent reports here in a focused update on the use of regadenoson for MPI.

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Original ArticleSafety of regadenoson in patients with end-stage liver disease

Abstract

Background

Methods and Results

Conclusion

Introduction

Section snippets

Patient Selection

Results

Discussion

Disclosures

Nuclear cardiac imaging: Principles and applications

Pharmacological stress testing

AASLD practice guidelines: Evaluation of the patient for liver transplantation

Hepatology

Usefulness of preoperative stress perfusion imaging in predicting prognosis after liver transplantation

Am J Cardiol

Regadenoson: A new myocardial stress agent

J Am Coll Cardiol

Usefulness of preoperative noninvasive radionuclide testing for detecting coronary artery disease in candidates for liver transplantation

Am J Cardiol

Myocardial perfusion and function: Single photon emission computed tomography

J Nucl Cardiol

Automatic quantification of ejection fraction from gated myocardial perfusion SPECT

J Nucl Med

Relation of left-ventricular dyssynchrony by phase analysis of gated SPECT images and cardiovascular events in patients with implantable cardiac defibrillators

J Nucl Cardiol

Corridor4DM: The Michigan method for quantitative nuclear cardiology

J Nucl Cardiol

Automated assessment of serial SPECT myocardial perfusion images

J Nucl Cardiol

The impact of viability assessment using myocardial perfusion imaging on patient management and outcome

J Nucl Cardiol

Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus

Am Heart J

Blunting of the heart rate response to adenosine and regadenoson in relation to hyperglycemia and the metabolic syndrome

Am J Cardiol

Original Article
Safety of regadenoson in patients with end-stage liver disease