Statin Needs to be Continued During Paxlovid Therapy in COVID-19

Vuorio, Alpo; Kovanen, Petri T.; Raal, Frederick J.

doi:10.1093/cid/ciac667

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…Importantly, a very recent study in the United Kingdom identified microangiopathic thrombosis as a common cause of myocardial injury in hospitalized COVID-19 patients with troponin elevation [40]. Regarding HeFH patients with COVID-19, both the severe hypercholesterolemia and the SARS-CoV-2 infection jointly cause CMD which, in combination, is likely to be more severe than in normolipidemic individuals [41].…”

Section: Coronary Microcirculationmentioning

confidence: 99%

“…As the listed statins are substrates for the hepatic cytochrome P450 (CYP) 3A4, and the ritonavir component of Paxlovid strongly inhibits CYP 3A4, coadministration of Paxlovid with any of the listed statins may increase their concentration to a toxic level [80]. However, it is important to continue statin treatment, particularly in HeFH patients with a high cardiovascular risk [81][82][83]. Accordingly, during NMV/r treatment, simvastatin or lovastatin should be substituted with either pravastatin or fluvastatin.…”

Section: Primarily Triglyceride-lowering Drugs (Fenofibrate)mentioning

confidence: 99%

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Familial hypercholesterolemia: The nexus of endothelial dysfunction and lipoprotein metabolism in COVID-19

Vuorio

Raal

Kovanen

2023

Current Opinion in Lipidology

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Purpose of reviewPatients with heterozygous familial hypercholesterolemia (HeFH) are at increased risk for COVID-19 cardiovascular complications in the acute phase of the infection. Elevated levels of LDL-C and often lipoprotein(a) are present from birth and lead to endothelial dysfunction, which is aggravated by a direct viral attack of the endothelial cells and their exposure to the toxic levels of circulating proinflammatory and prothrombotic mediators during the hyperinflammatory reaction typical of COVID-19. Recent findingsEvidence to date shows the benefit of lipid-lowering therapy in patients with COVID-19. In HeFH patients who are at much higher cardiovascular risk, the focus should, therefore, be on the effective lowering of LDL-C levels, the root cause of the greater cardiovascular vulnerability to COVID-19 infection in these patients. The ongoing use of statins and other lipid-lowering therapies should be encouraged during the ongoing COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19, particularly in HeFH patients. SummaryEpidemiologic registry data show that the incidence of myocardial infarction is increased in SARS-CoV-2infected HeFH patients. There is a need to study whether the risk for acute cardiovascular events is increased in the long-term and if there are changes in lipid metabolism after SARS-CoV infection(s) in patients with HeFH.

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Section: Coronary Microcirculationmentioning

confidence: 99%

Section: Primarily Triglyceride-lowering Drugs (Fenofibrate)mentioning

confidence: 99%

Familial hypercholesterolemia: The nexus of endothelial dysfunction and lipoprotein metabolism in COVID-19

Vuorio

Raal

Kovanen

2023

Current Opinion in Lipidology

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“…The computational and clinical studies of ARBs favor their development as strong competitors of the newly introduced Paxlovid, the antiviral drug Pfizer developed to treat COVID-19 patients [38,80,[88][89][90]. Importantly, there is evidence that the COVID-19 medication Paxlovid, of which nirmatrelvir is the main active ingredient (Pfizer, New York, NY, USA), may cause unwanted drug-drug interactions with medications commonly prescribed to patients with pre-existing cardiovascular diseases [91,92]. This, coupled with our results showing the inability of nirmatrelvir to modulate AngII-and AngA-mediated contraction even at clinically relevant doses, demonstrates the importance of investigating potential cardiovascular-protective pharmaceuticals to be used in conjunction with Paxlovid is essential.…”

Section: Arbs As a Covid-19 Treatmentmentioning

confidence: 99%

Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries

Gadanec,

Swiderski,

Apostolopoulos

et al. 2023

IJMS

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Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the placebo effect observed in hypertensive clinical trials. To determine this within physiology and to evaluate novel ARBs, we tested the ability of known angiotensin II receptor blockers (ARBs) (candesartan and telmisartan) used to treat hypertension and other cardiovascular diseases, as well as novel ARBs (benzimidazole-N-biphenyl tetrazole (ACC519T), benzimidazole-bis-N,N′-biphenyl tetrazole (ACC519T(2)) and 4-butyl-N,N0-bis[[20-2Htetrazol-5-yl)biphenyl-4-yl]methyl)imidazolium bromide (BV6(K+)2), and nirmatrelvir (the active ingredient in Paxlovid) to modulate vascular contraction in iliac rings from healthy male New Zealand White rabbits in responses to various vasopressors (angiotensin A, angiotensin II and phenylephrine). Additionally, the hemodynamic effect of ACC519T and telmisartan on mean arterial pressure in conscious rabbits was determined, while the ex vivo ability of BV6(K+)2 to activate angiotensin-converting enzyme-2 (ACE2) was also investigated. We show that commercially available and novel ARBs can modulate contraction responses at ultra-high dilutions to different vasopressors. ACC519T produced a dose-dependent reduction in rabbit mean arterial pressure while BV6(K+)2 significantly increased ACE2 metabolism. The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K+)2 to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.

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“…Unfortunately, the simultaneous use of Paxlovid and statin may result in serious interactions [ 44 ]. While it is essential to continue statin treatment during the 5-day Paxlovid treatment, simvastatin and lovastatin need to be substituted with another statin [ 45 , 46 ]. The substitution can be done with either pravastatin or fluvastatin.…”

Section: Lipid-lowering Drugs and Covid-19mentioning

confidence: 99%

Familial Hypercholesterolemia Patients with COVID-19—Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection

Vuorio¹,

Raal²,

Kovanen³

2022

Rev. Cardiovasc. Med.

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Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.

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Statin Needs to be Continued During Paxlovid Therapy in COVID-19

Cited by 5 publications

References 10 publications

Familial hypercholesterolemia: The nexus of endothelial dysfunction and lipoprotein metabolism in COVID-19

Familial hypercholesterolemia: The nexus of endothelial dysfunction and lipoprotein metabolism in COVID-19

Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries

Familial Hypercholesterolemia Patients with COVID-19—Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection

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