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Journal Articles
The following publications contain information about the Lexiscan phase 3 clinical studies as well as data from the clinical development of Lexiscan.
ADVANCE MPI (Phase 3) Studies
Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging: integrated ADVANCE-MPI Trial results. J Am Coll Cardiol Img. 2008;1:307-316.
Objectives:
- To compare the effects of age, gender, body mass index (BMI), and diabetes mellitus (DM) on the safety and efficacy of regadenoson stress MPI
- To assess the noninferiority of regadenoson to adenosine for the detection of reversible myocardial perfusion defects
Methods:
- Combined data from 2 identical double-blind, randomized, active-comparator, double-dummy, multicenter phase 3 trials (2015 patients, 109 centers)
- All patients had an adenosine study then were randomized to either regadenoson or adenosine in a 2:1 ratio
- Trial protocols limited the number of patients with "no to minimal" reversible defects, based on site investigator’s interpretation of the initial adenosine study, to ≤50% of the total randomized to guarantee assessment reflected the full range of disease severity
- Three expert blinded readers independently scored the images using a 17-segment model
- Reported symptoms were collected and rated as mild, moderate, or severe
- Based on predefined analysis, symptoms were combined into 7 groups (adverse reactions according to Adenoscan label) with a frequency greater than 10%
Results:
- Primary endpoint—noninferiority:
- Average agreement rates between adenosine-adenosine and adenosine-regadenoson were 0.62±0.03 and 0.63±0.02, respectively
- Within age, gender, BMI, and DM subgroups, average adenosine and regadenoson agreement rates were similar, and adenosine and regadenoson agreement rates were also similar for each initial study ischemia size category
- Secondary endpoints:
- Average agreement rates for adenosine-adenosine and adenosine-regadenoson were 0.76±0.03 and 0.77±0.02 for the presence and 0.77±0.02 and 0.78±0.02 for the absence of ischemia
- For both stress agents, simple agreement rates were also similar across age, sex, BMI, and DM subgroups
- Image quality: the majority of images were rated good or excellent (92%)
Conclusions:
- Regadenoson is as efficacious as adenosine in detecting ischemia regardless of age, gender, BMI, and DM
- Regadenoson can be safely administered as a fixed-unit bolus
Iskandrian AE, Bateman TM, Belardinelli L, et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007;14:645-658.
Objectives:
- To demonstrate noninferiority of regadenoson compared with adenosine by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson and adenosine-adenosine images, lay above a prespecified noninferiority margin (primary endpoint)
- To prospectively perform safety and tolerability comparisons
Methods:
- A multicenter, double-blind phase 3 trial of 784 patients was conducted
- Each patient underwent 2 sets of SPECT MPI studies—an initial study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine
Results:
- The average agreement rate based on the median of 3 independent, blinded readers was 0.63±0.03 for regadenoson-adenosine and 0.64±0.04 for adenosine-adenosine
- Side-by-side interpretation of regadenoson and adenosine images was comparable for detecting reversible defects
- A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than with adenosine (P=.013)
Conclusions:
- Regadenoson provides diagnostic information comparable to standard adenosine infusion
- No serious drug-related side effects occurred
- Regadenoson was better tolerated than adenosine
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Lexiscan (regadenoson) injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.
IMPORTANT SAFETY INFORMATION
Do not administer Lexiscan to patients with second- or third-degree AV block or sinus node dysfunction unless these patients have a functioning artificial pacemaker.
Fatal cardiac arrest, life-threatening ventricular arrhythmias, and myocardial infarction may result from the ischemia induced by pharmacologic stress agents. Hypersensitivity including anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria and rashes have occurred. Resuscitation equipment and trained staff should be immediately available before administering Lexiscan.
Adenosine receptor agonists, including Lexiscan, can depress the SA and AV nodes and may cause first-, second-, or third-degree AV block, or sinus bradycardia requiring intervention. In postmarketing experience, heart block (including third degree), and asystole within minutes of Lexiscan administration have occurred.
Adenosine receptor agonists, including Lexiscan, induce arterial vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, left main coronary artery stenosis, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. In postmarketing experience, transient ischemic attack, seizures and syncope have been observed.
Adenosine receptor agonists, including Lexiscan, may result in clinically significant increases in blood pressure in some patients. In postmarketing experience, cases of potentially clinically significant hypertension have been reported, particularly in patients with underlying hypertension and when low-level exercise was included in the MPI.
Adenosine receptor agonists, including Lexiscan, may cause dyspnea, bronchoconstriction and respiratory compromise. Appropriate bronchodilator therapy and resuscitative measures should be available prior to Lexiscan administration.
The most common adverse reactions (≥5%) to Lexiscan are dyspnea, headache, flushing, chest discomfort, angina pectoris or ST-segment depression, dizziness, chest pain, nausea, abdominal discomfort, dysgeusia, and feeling hot. Most adverse reactions began soon after dosing, and generally resolved within approximately 15 minutes, except for headache, which resolved in most patients within 30 minutes. Aminophylline was used as a reversal agent in 3% of patients.
In postmarketing experience, QTc prolongation, tremor, abdominal pain in association with nausea, vomiting, or myalgias, and diarrhea, fecal incontinence, wheezing and musculoskeletal pain have occurred.
Intravenous Adenoscan is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.
IMPORTANT SAFETY INFORMATION
Adenoscan is contraindicated in patients with second- or third-degree AV block, unless these patients have a functioning artificial pacemaker, sinus node disease, and known or suspected bronchoconstrictive or bronchospastic lung disease.
Fatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and nonfatal myocardial infarction have been reported coincident with Adenoscan infusion. Patients with unstable angina may be at greater risk. Appropriate resuscitative measures should be available.
Adenoscan is a potent peripheral vasodilator and can cause significant hypotension. The risk of hypotension may be higher in patients with cardiac or cerebrovascular insufficiency.
Adenoscan exerts a direct depressant effect on the SA and AV nodes and has the potential to cause first-, second- or third-degree AV block, or sinus bradycardia.
Increases in systolic and diastolic pressure have been observed.
Adenosine receptor agonists, including Adenoscan, may cause bronchoconstriction and respiratory compromise.
Atrial fibrillation has been reported in patients with Adenoscan infusion and may last from a few seconds to hours, however, patients spontaneously converted to normal sinus rhythm.
Most common adverse reactions (≥5%) to Adenoscan are flushing, chest discomfort, dyspnea, headache, discomfort of the throat, neck, or jaw, gastrointestinal discomfort, and lightheadedness/dizziness. Side effects with Adenoscan usually resolve quickly when the infusion is discontinued, although delayed or persistent effects have been observed.
Lexiscan is a registered trademark of Astellas US LLC. Other trademarks listed belong to their respective owners.
Lexiscan was developed in collaboration with Gilead Palo Alto, Inc. (formerly CV Therapeutics, Inc.).
©2011 Astellas Pharma US, Inc. All rights reserved. 011F-012-3727 LEX30155-MK