Is it justified to stop atorvastatin (statin) in a patient with a history of myocardial infarction to start Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

Management of Atorvastatin During Paxlovid Treatment in a Patient with Prior Myocardial Infarction

Atorvastatin should be temporarily discontinued during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) treatment for COVID-19 in this 73-year-old male with history of myocardial infarction, and can be safely resumed immediately after completing the antiviral course. 1, 2

Drug Interaction Mechanism and Risks

• Ritonavir in Paxlovid is a strong CYP3A4 inhibitor that significantly increases plasma concentrations of atorvastatin, which is primarily metabolized through the CYP3A4 pathway 1, 3
• The FDA label for Paxlovid specifically recommends considering temporary discontinuation of atorvastatin during the 5-day treatment course due to this interaction 1
• Unlike simvastatin and lovastatin (which are contraindicated with Paxlovid), atorvastatin does not need to be withheld prior to starting Paxlovid treatment 1
• The increased atorvastatin concentration from this interaction can potentially lead to myopathy including rhabdomyolysis 1, 4

Benefits of Paxlovid in High-Risk COVID-19 Patients

• Paxlovid reduces the risk of hospitalization by 39% and death by 61% in COVID-19 patients, with particularly strong benefits in patients over 65 years of age 5
• Patients with cardiovascular disease are at higher risk for progression to severe COVID-19, making them priority candidates for early antiviral therapy 3
• The 73-year-old patient with history of myocardial infarction falls into a high-risk category that would significantly benefit from Paxlovid treatment 5, 3

Management Strategy for Statin Therapy

• Temporarily discontinue atorvastatin during the 5-day course of Paxlovid treatment 1, 2
• Resume atorvastatin immediately after completing the 5-day Paxlovid course 2
• The short 5-day interruption of statin therapy poses minimal cardiovascular risk compared to the substantial benefits of Paxlovid in preventing COVID-19 progression 2, 5
• Alternative options if statin therapy is deemed absolutely necessary during Paxlovid treatment:
  • Switch to pravastatin or fluvastatin which have minimal CYP3A4 metabolism and fewer interactions with ritonavir 2
  • Consider dose reduction of atorvastatin if it must be continued, though temporary discontinuation is preferred 2, 4

Clinical Considerations and Monitoring

• Monitor for muscle symptoms during and after Paxlovid treatment if statin therapy is continued at a reduced dose 4
• The European Association of Percutaneous Cardiovascular Interventions (EAPCI) notes that when lopinavir/ritonavir is used in COVID-19 patients, atorvastatin should be administered at the lowest possible dose due to metabolism interactions 6
• The 5-day interruption of statin therapy is unlikely to significantly impact long-term cardiovascular outcomes, while untreated COVID-19 poses an immediate mortality risk 5, 3

Pitfalls to Avoid

• Do not continue atorvastatin at the regular dose during Paxlovid treatment due to risk of myopathy and rhabdomyolysis 1, 4
• Do not permanently discontinue statin therapy - ensure prompt resumption after completing the 5-day Paxlovid course 2
• Avoid substituting with simvastatin or lovastatin, which are explicitly contraindicated with Paxlovid 1
• Do not withhold Paxlovid treatment in this high-risk patient due to concerns about temporary statin discontinuation 5, 3