Highlights
- •Statins need to be continued during nirmatrelvir/ritonavir therapy in COVID-19.
- •Simvastatin use is contraindicated during nirmatrelvir/ritonavir therapy.
- •Pravastatin and fluvastatin can be safely used as a substitute for simvastatin.
- •Statin treatment is associated with an improved prognosis for COVID-19.
- •Withdrawal from statin therapy may also acutely worsen cardiovascular prognosis.
Keywords
We read with interest the Danish population-based study estimating the risk of significant drug-drug interactions (DDIs) with the antiviral component, nirmatrelvir, of the drug combination nirmatrelvir/ritonavir (NMV/r) in the age groups ≥65 years and ≥80 years [
[1]
]. The study highlights the potentially detrimental effects of DDIs if this antiviral treatment is used as part of polypharmacy in this elderly population at a high risk for the progression of SARS-CoV-2 infection to severe COVID-19.Regarding statin treatment and NMV/r DDIs, it was found that 15.45% of the study population in the age group ≥65 years used simvastatin or lovastatin and that the respective percentage among those aged ≥80 years was 17.70%. The percentages for atorvastatin in the age groups ≥65 and ≥80 years were 19.91% and 15.85%, respectively. Because simvastatin and lovastatin are contraindicated during NMV/r treatment, Larsen [
[1]
] recommends that “patients at low risk of atherosclerotic events could potentially pause the statin treatment during NMV/r administration”.For several reasons, we are concerned about the potential danger associated with the recommendation to discontinue statin treatment in the age group ≥65 years. First, according to the current guidelines, statins are not routinely prescribed to patients having a low risk for atherosclerotic cardiovascular disease (ASCVD) [
[2]
]. Moreover, the decision to use statin in older individuals is not evidence-based and, therefore, must be made individually [[3]
]. Second, it is challenging to estimate the actual ASCVD risk in older patients, especially those aged ≥75 years and who are free of clinically overt ASCVD [[4]
]. Among patients aged <75 years, the efficacy of statins used for primary prevention is well proven, and the relative risk reduction of major vascular events is about 20-30% for every 1 mmol/l reduction in low-density lipoprotein cholesterol [[5]
]. Third, in patients with COVID-19, several studies have shown that the use of statins is associated with an improved prognosis [- Mihaylova B
- Emberson J
- Blackwell L
- Keech A
- Simes J
- Barnes EH
- Voysey M
- Gray A
- Collins R
- Baigent C.
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
Lancet. 2012; 380 (Cholesterol Treatment Trialists' (CTT) Collaborators): 581-590https://doi.org/10.1016/S0140-6736(12)60367-5
[6]
]. In addition, the main protease (Mpro) of the SARS-CoV-2 virus adversely affects the microvascular endothelial cells in the brain, and statins may directly inhibit Mpro activity [[7]
]. Fourth, withdrawal from statin therapy may acutely worsen the prognosis of patients with non-ST-segment elevation myocardial infarction, even in patients without the additional cardiovascular burden caused by a viral infection [[8]
]. Finally, the option that statin withdrawal remains permanent is a major concern.Based on the previously mentioned considerations, we recommend that rather than discontinuing simvastatin treatment, simvastatin should be substituted by either pravastatin or fluvastatin [
[9]
]. By taking into account the prognosis of both COVID-19 and ASCVD, the patient would then be at low risk of side effects from statin therapy and will be guaranteed the best possible benefits from the statin treatment.- Vuorio A
- Kovanen PT
- Raal F.
Cholesterol-lowering drugs for high-risk hypercholesterolemia patients with COVID-19 while on Paxlovid™ therapy.
Future Virol. 2022; (b)https://doi.org/10.2217/fvl-2022-0060
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Ethical approval
Not applicable.
Author contributions
AV writing the first draft. AV, FR, PTK reviewing and editing to produce the final draft.
Declaration of competing interest
AV has received consultancy fees from Amgen and Novartis. PTK has received consultancy fees, lecture honoraria, and/or travel fees from Amgen, Novartis, Raisio Group, and Sanofi. FR has received research grants, honoraria, or consulting fees for professional input and/or lectures from Sanofi, Regeneron, Amgen, and Novartis.
References
- Assessing the proportion of the Danish population at risk of clinically significant drug-drug interactions with new oral antivirals for early treatment of COVID-19.Int J Infect Dis. 2022; 122: 599-601https://doi.org/10.1016/j.ijid.2022.06.059
- 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.Eur Heart J. 2020; 41: 111-188https://doi.org/10.1093/eurheartj/ehz455
- Evaluation and treatment of older patients with hypercholesterolemia: a clinical review.JAMA. 2014; 312: 1136-1144https://doi.org/10.1001/jama.2014.10924
- Statin therapy in older adults for primary prevention of atherosclerotic cardiovascular disease: the balancing act.American College of Cardiology. 2020; ([accessed 20 October 2022])
- The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.Lancet. 2012; 380 (Cholesterol Treatment Trialists' (CTT) Collaborators): 581-590https://doi.org/10.1016/S0140-6736(12)60367-5
- The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis.Ann Med. 2021; 53: 874-884https://doi.org/10.1080/07853890.2021.193316s5
- Statin needs to be continued during Paxlovid therapy in COVID-19.Clin Infect Dis. 2022; (a): ciac667https://doi.org/10.1093/cid/ciac667
- Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction.Arch Intern Med. 2004; 164: 2162-2168https://doi.org/10.1001/archinte.164.19.2162
- Cholesterol-lowering drugs for high-risk hypercholesterolemia patients with COVID-19 while on Paxlovid™ therapy.Future Virol. 2022; (b)https://doi.org/10.2217/fvl-2022-0060
Article info
Publication history
Published online: December 01, 2022
Accepted:
November 28,
2022
Received in revised form:
November 24,
2022
Received:
October 24,
2022
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© 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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- Drug-drug interaction with oral antivirals for early treatment of COVID-19 – Authors’ replyInternational Journal of Infectious DiseasesVol. 126Open Access
