Background: Regadenoson is predominantly renally metabolized. Patients with severe chronic kidney disease (CKD) experience more frequent gastrointestinal adverse effects (AE) from regadenoson. Aminophylline use following regadenoson reduces the incidence of regadenoson-related AE. We investigated whether patients with severe CKD receive incremental benefit from aminophylline administration in reducing regadenoson AE.
Methods: We performed post hoc analysis of the pooled database of the ASSUAGE and ASSUAGE-CKD trials. These were randomized placebo-controlled clinical trials which tested the benefit of intravenous aminophylline vs placebo after regadenoson injection in patients undergoing a clinically indicated stress MPI. Patients were categorized into two treatment arms: aminophylline vs placebo; and two groups: Severe CKD (GFR < 30 mL·min(-1)/1.73 m(2) or dialysis) and Control (GFR ≥ 30 mL·min(-1)/1.73 m(2)). The study endpoints were gastrointestinal AE, non-gastrointestinal AE and composite of any regadenoson AE.
Result: The pooled database of the two trials yielded 548 patients, of whom 274 patients received aminophylline and 274 received placebo. Aminophylline was associated with greater absolute risk reduction (ARR) in gastrointestinal AE among patients with severe CKD vs controls (25% vs 4%, p < .001). A significant interaction was identified between severe CKD and aminophylline in reducing gastrointestinal AE (p = .007), indicating greater reduction in gastrointestinal AE with aminophylline use among patients with severe CKD. Aminophylline use was associated with a trend toward greater ARR in any regadenoson-related AE (32% vs 21%, p = .08).
Conclusion: Aminophylline is associated with incremental benefit in reducing gastrointestinal AE in patients with severe CKD undergoing regadenoson stress MPI. Potentially, this population could be targeted for prophylactic administration of aminophylline in order to improve their overall experience with the test.
Keywords: ASSUAGE; adverse effects; aminophylline; chronic kidney disease (CKD); end-stage renal disease (ESRD); regadenoson.