Should atorvastatin (a statin) be continued or held in an adult patient with a history of atherosclerotic disease, specifically PAD and cardiovascular disease, while on daptomycin therapy?

Statin Management During Daptomycin Therapy in PAD Patients

Continue atorvastatin during daptomycin therapy in this patient with PAD and cardiovascular disease, as the cardiovascular mortality benefit of statin therapy far outweighs the theoretical risk of additive myopathy. 1

Rationale for Continuing Statin Therapy

Guideline-Mandated Statin Use in PAD

• Patients with PAD have established atherosclerotic cardiovascular disease (ASCVD), which includes peripheral artery disease by definition, making statin therapy a Class I recommendation. 1
• The 2018 ACC/AHA guidelines mandate high-intensity statin therapy for all patients under 75 years with clinical ASCVD (including PAD) to achieve ≥50% LDL-C reduction, with continuation even in patients over 75 who tolerate therapy. 1
• The 2024 ESC guidelines recommend an LDL-C goal of <1.4 mmol/L (55 mg/dL) with >50% reduction from baseline in all patients with atherosclerotic PAD. 1

Mortality and Morbidity Benefits

• Statin therapy in PAD patients reduces all-cause mortality by 42% (HR: 0.58,95% CI: 0.49-0.67) and cardiovascular death by 43% (HR: 0.57,95% CI: 0.40-0.74). 2
• Major adverse cardiovascular events (MACE) are reduced by 35% (HR: 0.65,95% CI: 0.51-0.80) and myocardial infarction rates by 41% (HR: 0.59,95% CI: 0.33-0.86). 2
• Amputation-free survival increases by 56% (HR: 0.44,95% CI: 0.30-0.58) and amputation risk decreases by 35% (HR: 0.65,95% CI: 0.41-0.89). 2

Risk Assessment of Concurrent Therapy

Myopathy Risk with Daptomycin-Statin Combination

• While both daptomycin and statins can independently cause myopathy, there is no guideline recommendation or FDA mandate to discontinue statins during daptomycin therapy. 1
• The theoretical additive myopathy risk can be mitigated through clinical monitoring rather than statin discontinuation. 3

Monitoring Strategy During Concurrent Therapy

• Obtain baseline creatine kinase (CK) levels before initiating daptomycin in patients already on statins. 3
• Monitor CK levels weekly during the first month of daptomycin therapy, then every 2 weeks if stable. 3
• Instruct the patient to immediately report muscle pain, weakness, or dark urine. 3
• Discontinue atorvastatin only if CK rises to >10 times upper limit of normal or if symptomatic myopathy develops. 3

Alternative Approach if Statin Must Be Held

When Temporary Discontinuation Is Justified

• If the patient develops symptomatic myopathy (muscle pain with CK elevation >5-10x ULN) during daptomycin therapy, temporarily hold atorvastatin. 3
• If daptomycin course is brief (≤2 weeks) and patient has severe baseline myopathy risk factors (elderly, frail, renal dysfunction), consider temporary hold with close monitoring. 3

Bridging Lipid-Lowering Therapy

• If atorvastatin must be held, immediately initiate ezetimibe 10 mg daily as it does not cause myopathy and provides 15-20% additional LDL-C reduction. 1, 3
• For statin-intolerant patients with atherosclerotic PAD who don't achieve LDL-C goals on ezetimibe, add bempedoic acid (which also lacks myopathy risk) or consider PCSK9 inhibitors. 1, 3

Resumption After Daptomycin

• Resume atorvastatin immediately upon completion of daptomycin therapy if it was temporarily held. 1
• If myopathy occurred, wait until CK normalizes, then rechallenge with a lower-intensity statin or alternative agent. 3

Common Pitfalls to Avoid

• Never discontinue statins in PAD patients without implementing alternative lipid-lowering therapy, as this dramatically increases cardiovascular mortality risk. 1, 2
• Do not assume that daptomycin automatically contraindicates statin use—this is not supported by guidelines or drug labels. 1
• Avoid using only clinical symptoms to monitor for myopathy; obtain objective CK measurements as patients may have asymptomatic CK elevation. 3
• Do not restart statins at the same dose if symptomatic myopathy occurred; use a lower intensity or alternative agent with rechallenge. 3
• Remember that the cardiovascular benefits of statins in PAD (42% mortality reduction) vastly exceed the risk of myopathy (typically <1% with monitoring). 2