How to manage gouty arthritis with colchicine and allopurinol in patients with Heart Failure with reduced Ejection Fraction (HFrEF)?

Management of Gouty Arthritis in HFrEF Patients

For acute gout flares in HFrEF patients, use colchicine as first-line therapy, and allopurinol can be safely used for urate-lowering therapy with appropriate precautions, though its cardiovascular safety remains uncertain. 1

Acute Gout Flare Management

Colchicine as Preferred Agent

• Colchicine is the preferred treatment for acute gout attacks in HFrEF patients over NSAIDs, as NSAIDs should be strictly avoided due to risks of fluid retention, worsening heart failure, and renal impairment. 1

• Colchicine appears safe in HFrEF and may provide cardiovascular benefit—a retrospective study showed reduced in-hospital mortality (2.1% vs 6.5%, p=0.009) when colchicine was used during acute decompensated heart failure admissions. 2

• Recent evidence demonstrates colchicine prophylaxis reduces cardiovascular events compared to NSAIDs, with a hazard ratio of 0.64 (95% CI 0.45-0.90) for MACE. 3

Critical Colchicine Precautions

• Do not use colchicine in patients with very severe renal dysfunction (CrCl <30 mL/min), as toxicity risk increases substantially. 1, 4

• Monitor for diarrhea as a common adverse effect, which may complicate volume management in HFrEF. 1

Alternative for Monoarticular Gout

• Intra-articular corticosteroids are an effective alternative for single-joint involvement. 1

• Avoid systemic corticosteroids when possible, as they cause sodium and water retention that can precipitate heart failure decompensation. 1

Urate-Lowering Therapy with Allopurinol

Allopurinol Use in HFrEF

• Allopurinol may be used for gout prophylaxis in HFrEF, though the ESC guidelines explicitly state its safety in HFrEF is uncertain. 1

• Despite this uncertainty, allopurinol is considered safer than febuxostat in cardiovascular disease—febuxostat carries an increased risk of cardiovascular death and heart failure hospitalization. 5

• Start allopurinol at low doses (≤100 mg/day, even lower with CKD stage ≥3) and titrate gradually to target serum uric acid <6 mg/dL. 1, 6

Mandatory Anti-inflammatory Prophylaxis

• Always initiate concomitant anti-inflammatory prophylaxis when starting allopurinol to prevent paradoxical gout flares during the initial months of therapy. 1, 6

• Use colchicine 0.5-1 mg daily for prophylaxis, which reduces flare frequency from 77% to 33% (NNT=2) when starting allopurinol. 1, 7

• Continue prophylaxis for 3-6 months minimum, with ongoing evaluation for persistent flares. 1, 6

Dosing Adjustments for Renal Impairment

• In CKD stage ≥3 (common in HFrEF patients on diuretics), start with even lower allopurinol doses (50-100 mg/day) and monitor closely. 1, 6, 4

• Despite dose reductions needed for renal impairment, allopurinol can still be titrated above 300 mg/day to achieve target uric acid levels with careful monitoring. 1

Key Clinical Pitfalls

Diuretic-Induced Hyperuricemia

• Recognize that loop diuretics (standard HFrEF therapy) commonly precipitate or worsen gout. 1

• Consider allopurinol prophylaxis in HFrEF patients on chronic diuretics who develop hyperuricemia or recurrent gout. 1

Absolute Contraindications

• Never use NSAIDs in HFrEF patients with gout—they cause diuretic resistance, acute kidney injury, fluid retention, and heart failure exacerbation. 1, 5

• NSAIDs increase MACE risk compared to colchicine (HR 1.56,95% CI 1.11-2.17) and compared to no prophylaxis (HR 1.50,95% CI 1.17-1.91). 3

Monitoring Requirements

• Check renal function and electrolytes 1-2 weeks after initiating or increasing allopurinol dose, as HFrEF patients are vulnerable to acute kidney injury. 1

• Monitor for allopurinol hypersensitivity syndrome, particularly in patients with CKD—lower starting doses mitigate this risk. 1