RETRACTED ARTICLE: Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI

See related article, pp. 1062-1070 Aminophylline has long been used in the reversal of vasodilators used for myocardial perfusion imaging. However, in 2010, manufacturers of aminophylline reported shortages making a search for an alternative a high priority. In this issue of the Journal, Doral et al 1 at the University of Rochester report their evaluation of the effectiveness of intravenous (IV) and oral caffeine as an alternative to IV aminophylline in the reversal of adverse effects of regadenoson. They randomized 241 patients to receive 100 mg of IV aminophylline, 60 mg of IV caffeine, or a caffeinated beverage, either diet soda or caffeinated coffee, if adverse symptoms occurred. They provided a 5-minute delay before offering a reversal agent to allow for adequate myocardial extraction of the radiotracer. Exercise was encouraged during administration of regadenoson and performed in 22% of patients. 2 The primary endpoint was complete resolution (CR) of symptoms. If a patient did not achieve CR, they were classified into incomplete response (IR), predominant response (PRE), partial response (PR), or no response (NR). PRE was defined as C50% resolution of the number of symptoms; PR was defined as less than 50% resolution of the number of symptoms. A secondary end point was time from initiation of the reversal agent until CR.

supporting

confidence: 81%

“…13 Doran et al used a low threshold for reversal in their study, reversing 63% of patients. 1 Most labs choose a higher threshold and reverse a much lower percentage of patients. If a patient is reversed, we recommend waiting 3 minutes following radiotracer administration.…”

mentioning

confidence: 99%

Intravenous caffeine: An alternative to aminophylline to reverse adverse effects during regadenoson myocardial perfusion imaging

Jolly

Thomas

2017

“…This agent is administered via either an IV or oral route. Both oral and IV caffeine were recently compared in a randomized controlled fashion to IV aminophylline by Doran et al17 and were shown to provide rapid and safe reversal of vasodilator-induced adverse effects during SPECT MPI. This study evaluated the effect of reversal agents on patient-reported symptoms in a series of 241 consecutive patients presenting to the stress laboratory and undergoing regadenoson stress.…”

Section: Alternative Non-aminophylline Based Vasodilator Stress Revermentioning

confidence: 99%

“…Rates of complete or predominant reversal were 100% with IV aminophylline, 96% with IV caffeine ( P = NS vs aminophylline), and 84% with PO caffeine ( P = 0.003 vs IV aminophylline). Of the 37 patients in the oral caffeine group, 19 assigned to oral caffeine crossed over to receive IV caffeine based on concern the symptoms might be too severe for oral caffeine to be effective 17…”

Section: Alternative Non-aminophylline Based Vasodilator Stress Revermentioning

confidence: 99%

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR

Abidov

Dilsizian

Doukky

et al. 2019

Self Cite

Pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols. Electronic supplementary material The online version of this article (10.1007/s12350-018-01548-0) contains supplementary material, which is available to authorized users.

“…16 A recent study investigated the use of IV and oral caffeine as a potential alternative to aminophylline for the reversal of regadenoson-induced adverse effects. 17 The significance of prior caffeine consumption on regadenosoninduced coronary hyperemia and the diagnostic sensitivity of MPI for detection of perfusion abnormalities have been recently debated in the Journal. [18][19][20][21][22] Our view is that moderate caffeine consumption (i.e., B2 cups of coffee more than 1 hour prior to presentation to the stress laboratory) does not alter coronary flow reserve to such an extent to significantly impact myocardial perfusion pattern on MPI.…”

mentioning

confidence: 99%

Effect of aminophylline administration on the diagnostic yield of vasodilator myocardial perfusion imaging

Daya

Hage

2017

The last few decades have witnessed a steady increase in the proportion of myocardial perfusion imaging (MPI) tests that utilize pharmacologic stress instead of exercise. 1 Currently regadenoson, a pyrazole derivative of adenosine selective for the A 2A receptor, is the most commonly used vasodilator agent accounting for more than 80% of all pharmacological stress tests performed in the USA. 2 The widespread utilization of regadenoson is supported by multiple factors including its similar diagnostic and prognostic performance to adenosine when used for MPI, the simpler and more rapid infusion protocol, and the better safety profile in specific patient groups. 3-6 Although better tolerated by patients, regadenoson shares with adenosine similar adverse effects such as flushing, headaches, and gastrointestinal symptoms. 3,7 Aminophylline, a nonselective adenosine receptor antagonist, has been available on the market for decades and used to reverse the adverse effects of dipyridamole and adenosine and more recently been shown to be safe and effective for use with regadenoson. 8,9 In this issue of the Journal, Fughhi et al. 10 address the concern that use of aminophylline to ameliorate the adverse effects of regadenoson may reverse its effects on coronary vasodilation and subsequent myocardial hyperemia reducing the sensitivity of MPI for detecting perfusion abnormalities. The data for the current study were pooled from two double-blinded, placebo-controlled randomized clinical trials, the ASSUAGE and ASSUAGE-CKD trials, 9,11 which demonstrated the effectiveness of aminophylline in attenuating the adverse effects associated with regadenoson in patients undergoing MPI. In both trials, patients were randomized to receive 75 mg of intravenous aminophylline or placebo administered at 90 seconds after radioisotope injection (*2 minutes following regadenoson). The primary end point of the current report was the degree of reversibility of the perfusion defect on imaging as measured by the semi-quantitative summed difference score (SDS). The secondary end point was the presence of myocardial ischemia as defined by SDS C2. The authors also examined the effect of aminophylline use on the prognostic value of myocardial ischemia detection by MPI for cardiac events including cardiac death, myocardial infarction (MI), and coronary revascularization over a follow-up period of 29 ± 14 months.The myocardial ischemic burden (primary outcome) and the presence of myocardial ischemia (secondary outcome) on MPI were similar between the two groups. However, there was a trend towards a higher proportion of abnormal perfusion (summed stress score, SSS C4, 34% vs 27%, P = .08) in the placebo group that the authors attributed to the significantly higher rate of prior MI (20% vs 13%, P = .03) in this group. To account for this imbalance, the authors performed a sensitivity analysis in patients without clinical or MPI evidence (summed rest score, SRS C4) of prior MI, and demonstrated similar prevalence of myocardial ischemia and abnormal perfusio...