Statin benefits patients with severe COVID-19 while vitamin C is ‘ineffective'

A common cholesterol-lowering drug may improve outcomes for critically ill patients with COVID-19, while high dose vitamin C is ineffective.

These are the latest findings to come from the REMAP-CAP study, the world’s largest trial of multiple interventions for critically ill adults with COVID-19, led by Imperial College London and the Intensive Care National Audit & Research Centre (ICNARC) in the UK.

The study finds that simvastatin, a common and inexpensive drug used to reduce cholesterol, has a very high probability (96%) of improving survival and reducing length of time patients need support in an intensive care. This is equivalent to one life saved for every 33 patients treated with simvastatin.

Our work to date through this landmark trial has helped to improve the treatment for some of the sickest patients with COVID-19. Professor Anthony Gordon Department of Surgery & Cancer

In a separate analysis, researchers also found the use of intravenous, high-dose vitamin C for hospitalised patients with COVID-19 was found to be ineffective, and potentially even harmful.

According to the researchers, the findings are likely to improve outcomes in critically ill patients with COVID-19, and help healthcare professionals internationally to improve the treatment of patients.

The work, funded and supported by the National Institute for Health and Care Research (NIHR), is published in two papers today (Wednesday, 25 October) in the journals JAMA (vitamin C) and NEJM (simvastatin).

Professor Anthony Gordon, UK Chief Investigator for REMAP-CAP, from Imperial College London’s Department of Surgery and Cancer and Consultant in Intensive Care Medicine at Imperial College Healthcare NHS Trust, said: “Our work to date through this landmark trial has helped to improve the treatment for some of the sickest patients with COVID-19.

“Working with partners in hospitals around the world, we’ve been able to generate real world evidence to show which treatment combinations are most effective in the treatment of severe COVID-19.

“To have both of these landmark results from REMAP-CAP published simultaneously is testament to the ability of this trial to efficiently evaluate multiple interventions. We want to thank all the patients, clinicians, and research staff who have contributed to advancing knowledge to inform the treatment of COVID-19, and continue to contribute to this ground-breaking trial.”

Simvastatin benefits

In the study 2,684 critically ill patients were included at 141 hospitals across 13 countries, Simvastatin was shown to have a very high probability (96%) of improving outcomes (a combination of survival and length of time patients need support in an intensive care unit) when started as a treatment for critically ill patients with COVID-19, and a 92% chance of improving survival at three months.

Researchers say the simvastatin finding is highly likely to improve outcomes in critically ill patients with COVID-19 and will help healthcare professionals internationally to improve the treatment of patients with severe disease.

Professor Danny McAuley, Professor and Consultant in Intensive Care Medicine at the Royal Victoria Hospital and Queen's University Belfast and lead investigator for the Simvastatin Domain of REMAP-CAP said: "These results are really encouraging as they have shown that treatment with simvastatin is highly likely to improve outcomes in critically ill patients with COVID-19. This research will help healthcare professionals internationally to improve the treatment of patients with COVID-19."

Vitamin C findings

In the second analysis, researchers examined high-dose vitamin C in COVID-19, finding evidence that it is not beneficial for patients.

In the largest trial of vitamin C, harmonizing two clinical trials (REMAP-CAP and LOVIT-COVID), more than 2,500 patients in 20 countries took part in the study, including both critically ill and non-critically ill patients with COVID-19 in hospital.

Participants received high-dose, intravenous infusions of vitamin C, around 100 times the strength of vitamin C supplements available in high street stores.

Analysis shows that high dose vitamin C did not improve outcomes for patients. This part of the trial was stopped once researchers had evidence that the treatment was not effective and, after a full analysis of the data, the results indicated that it may even be harmful.*

The team advise that clinicians should not use intravenous vitamin C in treatment of patients with COVID-19.

Dr Neill Adhikari, co-lead investigator for the LOVIT-COVID trial and of the Vitamin C Domain of REMAP-CAP, said: “Harnessing the power of global collaboration, the harmonized REMAP-CAP and LOVIT-COVID trials have investigated vitamin C, a potential therapy for COVID-19, and have shown it to be ineffective and probably harmful. The results from this trial suggest that the use of vitamin C in hospitalised COVID-19 patients should be de-adopted.”

Ongoing study 

REMAP-CAP began investigating treatments for COVID-19 in March 2020, enrolling hospitalised patients with either moderate or severe (requiring ICU care) COVID-19 disease.

The study design randomises patients to multiple combinations of treatments, enabling researchers to evaluate different treatments for COVID-19, including antivirals, drugs which modulate the immune response, and therapies that modulate or support other vital aspects of the body's response to the virus.

In total, over 2,000 patients in 15 countries have been enrolled at more than 260 hospitals worldwide and randomised to multiple treatment combinations. The effects of interventions are assessed separately for moderate and severely ill patients.

The latest findings on simvastatin and vitamin C add to previous REMAP-CAP findings, which found that arthritis drugs tocilizumab and lopinavir/ritonavir, as well as hydrocortisone steroid treatment, improved recovery among critically ill COVID-19 patients.

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This article is based on materials from the National Institute for Health and Care Research (NIHR).

‘Simvastatin in Critically Ill Patients with Covid-19’ by The REMAP-CAP Investigators is published in NEJM. DOI: https://doi.org/10.1056/NEJMoa2309995 

‘Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials’ by The LOVIT-COVID Investigators and the REMAP-CAP Investigators is published in JAMA. DOI: https://doi.org/10.1001/jama.2023.21407

*The possible harm isn’t “proven” because as soon as researchers found vitamin C wasn’t effective they stopped the trial. After analysing the full result the team found there is a high probability it is harmful, but don’t know exactly what the harm was. Patients receiving vitamin C in the trial had lower survival rates and spent longer receiving support in ICU.