The efficacy and safety of Lexiscan were determined relative to Adenoscan® (adenosine) injection in two phase 3, randomized, double-blind, noninferiority, pivotal studies—ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI).1,2
In 2 pivotal trials, Lexiscan was evaluated in 2015 patients (median age of 66 years) with known or suspected CAD indicated for pharmacologic stress MPI.1
All patients underwent a baseline scan with Adenoscan, and were randomized in a 2:1 ratio to either Lexiscan or Adenoscan for a second stress scan with the same radionuclide imaging protocol as the baseline scan.1,3
CABG = coronary artery bypass graft;
MI = myocardial infarction;
PTCA = percutaneous transluminal coronary angioplasty.
aOn day of dosing with blinded study medication.
Demonstrate noninferiority in the strength of agreement between sequential Adenoscan and Lexiscan images, and the strength of agreement between 2 sequential Adenoscan images for detecting the extent of reversible perfusion defects.3
Lexiscan was found to be similar to Adenoscan in assessing the extent of reversible perfusion defects.1
Regardless of age, gender, BMI, or diabetes, Lexiscan images were similar to Adenoscan images in detecting reversible myocardial perfusion defects.2
BMI = body mass index; CI = confidence interval; SE = standard error.
The overall incidence of adverse reactions was 80% for Lexiscan and 83% for Adenoscan. Aminophylline was used to treat reactions in 3% of patients in the Lexiscan group and 2% of patients in the Adenoscan group. Most adverse reactions began soon after dosing, and generally resolved within ≈15 minutes, except for headache which resolved in most patients within 30 minutes.1
PAC = premature atrial contraction; PVC = premature ventricular contraction.
a12-lead electrocardiograms (ECGs) were recorded before and for up to 2 hours after dosing.
bIncludes rhythm abnormalities (PACs, PVCs, atrial fibrillation/flutter, wandering atrial pacemaker, supraventricular or ventricular arrhythmia) or conduction abnormalities, including atrioventricular (AV) block.
The majority of study patients had an increase in heart rate and a decrease in blood pressure within 45 minutes after Lexiscan administration.1
bpm = beats per minute.
ADVANCE MPI Studies 1 and 2
Lexiscan® (regadenoson) injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress.
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 and nonfatal myocardial infarction, ventricular arrhythmias, and cardiac arrest have occurred following Lexiscan injection. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to Lexiscan. Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan. Adhere to the recommended duration of injection. As noted in an animal study, longer injection times may increase the duration and magnitude of increase in coronary blood flow. If serious reactions to Lexiscan occur, consider the use of aminophylline, an adenosine antagonist, to shorten the duration of increased coronary blood flow induced by Lexiscan.
Sinoatrial and Atrioventricular Nodal Block
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.
Atrial Fibrillation/Atrial Flutter
New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported following Lexiscan injection.
Hypersensitivity, Including Anaphylaxis
Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria and rashes have occurred. In clinical trials, hypersensitivity reactions were reported in fewer than 1 percent of patients.
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 attacks, 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 and following Lexiscan administration.
Lexiscan may lower the seizure threshold; obtain a seizure history. New-onset or recurrence of convulsive seizures has occurred following Lexiscan injection. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with Lexiscan injection. Methylxanthine use is not recommended in patients who experience a seizure in association with Lexiscan administration.
Cerebrovascular Accident (Stroke)
Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of Lexiscan including hypotension or hypertension may be associated with these adverse reactions.
In clinical trials, the most common adverse reactions (≥5%) to Lexiscan were 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, the following additional adverse reactions have occurred: supraventricular tachyarrhythmias, acute coronary syndrome (ACS), tremor, QTc prolongation, abdominal pain in association with nausea, vomiting, or myalgias, diarrhea, fecal incontinence, wheezing and musculoskeletal pain.