In a statin‑intolerant adult with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who is taking ezetimibe 10 mg daily and bempedoic acid 180 mg daily, what gout symptoms should be monitored and how should they be managed?

Gout Monitoring and Management in Patients on Bempedoic Acid and Ezetimibe

In statin-intolerant adults taking ezetimibe 10 mg and bempedoic acid 180 mg daily, monitor for new-onset joint pain, swelling, and warmth—particularly in the great toe, ankle, or knee—because bempedoic acid raises serum uric acid by approximately 0.8 mg/dL and triples the risk of acute gout attacks compared to placebo. 1

Baseline and Ongoing Monitoring

• Measure baseline serum uric acid before initiating bempedoic acid and recheck periodically (every 3–6 months) to identify hyperuricemia early. 1

• Educate patients to report acute onset of severe joint pain, erythema, or swelling immediately, as these symptoms indicate possible gout flare requiring prompt intervention. 1

• Hyperuricemia occurs approximately four-fold more frequently with bempedoic acid than placebo, and clinical gout attacks are three-fold more common. 1

Clinical Presentation of Gout to Monitor

• Classic monoarticular arthritis affecting the first metatarsophalangeal joint (podagra) is the most common initial presentation; however, ankles, knees, wrists, and fingers may also be involved. 1

• Look for sudden-onset severe pain (often nocturnal), joint erythema, warmth, swelling, and exquisite tenderness that peaks within 12–24 hours. 1

• In patients with established gout, bempedoic acid may trigger recurrent flares or polyarticular involvement. 1

Management Algorithm When Gout Develops

Step 1: Acute Gout Treatment

• Initiate urate-lowering therapy if clinical gout develops while continuing bempedoic acid, as the cardiovascular benefit of LDL-C reduction typically outweighs gout risk in high-risk ASCVD patients. 1

• Treat acute flares with NSAIDs (if renal function permits), colchicine, or corticosteroids according to standard gout management protocols. 1

Step 2: Long-Term Urate Management

• Start allopurinol or febuxostat to maintain serum uric acid <6 mg/dL, which prevents recurrent attacks and allows continuation of bempedoic acid for cardiovascular protection. 1

• Consider prophylactic colchicine 0.6 mg daily during the first 3–6 months of urate-lowering therapy initiation to prevent flares. 1

Step 3: Reassess Lipid Therapy if Gout is Refractory

• If gout becomes uncontrolled despite optimal urate-lowering therapy, discontinue bempedoic acid and substitute a PCSK9 inhibitor (alirocumab, evolocumab, or inclisiran), which lowers LDL-C by 50–60% without affecting uric acid. 2, 1

• PCSK9 inhibitors are well-tolerated in statin-intolerant patients and carry a Class I recommendation for very high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated therapy. 2

Other Musculoskeletal Adverse Effects to Monitor

• Tendon rupture is rare (0.5% vs. 0% placebo) but serious; instruct patients to report unexplained tendon pain, and discontinue bempedoic acid immediately if rupture is confirmed. 1

• Muscle spasms, back pain, and extremity pain occur at placebo-comparable rates, but bempedoic acid produces markedly fewer muscle-related adverse events than statins because it is activated only in the liver. 1, 3

Common Pitfall to Avoid

• Do not discontinue bempedoic acid at the first sign of hyperuricemia without symptoms; asymptomatic hyperuricemia alone does not require drug cessation, but warrants closer monitoring and patient education about gout symptoms. 1

• Failing to check baseline uric acid leaves you unable to quantify the drug's contribution to any subsequent gout flare, complicating management decisions. 1