What is the preferred pharmacologic stress agent for patients with End-Stage Renal Disease (ESRD)?

Preferred Pharmacologic Stress Agent in ESRD

Regadenoson is the preferred pharmacologic stress agent for patients with end-stage renal disease (ESRD), as it has been specifically studied and FDA-approved for use in this population without dose adjustment required. 1

Evidence Supporting Regadenoson in ESRD

FDA Approval and Safety Profile

• The FDA label explicitly states that no dose adjustment is needed in patients with renal impairment, including patients with end-stage renal disease and/or dependent on dialysis 1
• This represents a formal label update from January 2017 based on accumulating post-marketing safety data 2
• While regadenoson is predominantly renally excreted (57% unchanged in urine), the plasma concentration-time profile in the early stages after dosing—when clinically meaningful pharmacologic effects occur—is not significantly altered even in severe renal impairment 1

Clinical Safety Data in ESRD

• The largest retrospective study of 277 consecutive ESRD patients demonstrated that regadenoson was well tolerated with a safety profile similar to patients with normal renal function, with no medication-related hospitalizations, serious events, or deaths within 30 days 3
• Hemodynamic responses (heart rate increase and blood pressure changes) were comparable between ESRD and control groups 3
• The first prospective evaluation (ASSUAGE trials) in 146 ESRD subjects confirmed no serious adverse events and similar overall adverse effect incidence (74% vs 75%) compared to controls 4

Pharmacokinetic Considerations

• Although elimination half-life and AUC increase with worsening renal function, the maximum plasma concentrations and early-phase concentration-time profiles remain similar across all degrees of renal impairment 1
• This pharmacokinetic profile explains why clinical efficacy and safety are preserved despite reduced renal clearance 1, 2
• Regadenoson is dialyzable in vitro, though specific pharmacokinetic data in patients on dialysis has not been formally assessed 1

Alternative Agents: Why Not Adenosine?

While adenosine (ADENOSCAN) is also used for pharmacologic stress testing, regadenoson offers practical advantages in ESRD:

• Regadenoson requires a single 10-second bolus injection versus adenosine's 4-6 minute continuous infusion 2
• The extensive safety database specifically in ESRD patients makes regadenoson the evidence-based choice 3, 4
• No studies have demonstrated superior safety or efficacy of adenosine over regadenoson in the ESRD population

Clinical Pearls and Monitoring

Expected Adverse Effects

• Common side effects include headache (25%), dyspnea (19%), chest discomfort (15%), nausea (15%), and flushing (12%), which occur at similar rates regardless of renal function 5
• ESRD patients may experience slightly higher rates of diarrhea (29% vs 14%) and lower rates of dizziness (19% vs 44%) compared to controls 4
• All adverse effects are typically self-limited and resolve without intervention 3, 4

Hemodynamic Monitoring

• Monitor for hypotension, particularly in elderly patients (≥75 years), who have a 2% incidence compared to <1% in younger patients 1
• Expect modest decreases in systolic blood pressure (approximately 11 mmHg) and increases in heart rate (approximately 20 bpm) 3

Special Considerations

• No increased risk of arrhythmias, ST-segment deviation, or atrioventricular block in ESRD patients 4
• No clinically meaningful changes in estimated GFR from baseline to 24 hours post-dose 5