Severe chronic kidney disease as a predictor of benefit from aminophylline administration in patients undergoing regadenoson stress myocardial perfusion imaging: A substudy of the ASSUAGE and ASSUAGE-CKD trials.

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.

The safety and tolerability of regadenoson in patients with end-stage renal disease: the first prospective evaluation.

BACKGROUND: There has not been any prospective evaluation of the safety and tolerability of regadenoson (REG)-stress in patients with end-stage renal disease (ESRD). METHODS: From the pooled database of two identically designed randomized, double-blinded, placebo-controlled clinical trials, ASSUAGE and ASSUAGE-CKD (IV-aminophylline vs placebo following REG-stress), we extracted the placebo-treated subjects to form 2 study groups: ESRD (dialysis or GFR < 15 mL/minute/1.73 m(2)) and control (GFR ≥ 30). The incidence of REG adverse effects and the hemodynamic and ECG responses to REG-stress were compared. RESULTS: We identified 146 ESRD subjects and 97 controls. There was no significant difference in the incidence of the composite of any REG adverse effect [ESRD 108 (74%) vs control 73 (75%), P = .82]. ESRD patients seem to have excess incidences of diarrhea [42 (29%) vs 14 (14%), P = .009] and fewer events of dizziness [28 (19%) vs 43 (44%), P < .001]. There were no serious adverse events in either group. There was no significant difference in the incidence of ST-segment deviation, tachyarrhythmias, atrioventricular block, or hypotension. CONCLUSION: This is the first prospective study to confirm the safety and tolerability of REG in patients with ESRD.

Attenuation of the side effect profile of regadenoson: a randomized double-blind placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging and have severe chronic kidney disease--the ASSUAGE-CKD trial.

A subgroup analysis of the ASSUAGE trial suggested that the standardized intravenous aminophylline administration following regadenoson-stress leads to substantial attenuation of regadenoson adverse-effects in patients with severe chronic kidney disease (CKD). In a randomized, double-blinded, placebo-controlled clinical trial of patients with stage 4 and 5 CKD, we compared the frequency and severity of regadenoson adverse-effects in those who received 75 mg of intravenous aminophylline versus a matching placebo administered 90 s post-radioisotope injection. Consecutive 300 patients with severe CKD (36% women; 86% end-stage renal disease; age 55 (±13) years) were randomized to receive aminophylline (n = 150) or placebo (n = 150). In the aminophylline arm, there was 65% reduction in the incidence of the primary endpoint of diarrhea (9 (6.0%) vs. 26 (17.3%), P = 0.002), 51% reduction in the secondary endpoint of any regadenoson adverse-effect (47 (31.3%) vs. 96 (64%), P < 0.001) and 70% reduction in headache (16 (10.7%) vs. 54 (36%), P < 0.001). The stress protocol was better tolerated in the aminophylline group (P = 0.008). The quantitative summed difference score, as a measure of stress-induced ischemic burden, was similar between the study groups (P = 0.51). In conclusion, the routine standardized administration of intravenous aminophylline in patients with severe CKD substantially reduces the frequency and severity of the adverse-effects associated with regadenoson-stress without changing the ischemic burden. [NCT01336140].