April 6, 2020

expert reaction to preprint on COVID-19, high blood pressure, and high blood pressure drugs

A preprint, posted to MedRxiv, reports on COVID-19, high blood pressure, and high blood pressure drugs.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

Is this good research; is it robust?

“It is not high quality; it is a small observational study (not as far as I can tell a case-control study as stated by the authors).  Comparisons are made between groups according to a retrospective classification of treatments.  There is essentially no adjustment for the many potential confounding variables.  The findings simply cannot be relied upon to draw important conclusions over the benefits or possible harms of treatment with Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.  There is no evidence that suggests that they are harmful, but any benefit is little more than speculative.

What are its strengths and limitations?

“Its only strength is that a lot of clinical data were collected in a situation where Covid-19 was having notable effects.  Its key limitations are that not only was treatment not allocated randomly, but also no adjustment was made for possible differences in clinical characteristics that might account for observed differences between treatments.

Is this peer-reviewed research or preliminary data?

“This is not yet peer-reviewed and it is very unlikely that any major journal would publish it without major re-analysis.

What are the implications; or is it too early for there to be any?

“As noted, it does not provide evidence for harm of these drugs, but it neither provides evidence for their efficacy or even absence of harms in practice in patients with Covid-19.”

Dr Katrina Pollock, Senior Clinical Research Fellow in Vaccinology and Honorary Consultant, Department of Infectious Disease, Imperial College London, said:

Is this good research; is it robust?

“This is a small retrospective study and is not as robust as a full clinical trial.

What are its strengths and limitations?

“It provides some early data on important questions, which need further investigation, about co-morbidities and COVID-19, particularly hypertension, and commonly used medications for high blood pressure.  However the study was too small to answer these questions.

Is this peer-reviewed research or preliminary data?

“The research has not yet been peer-reviewed and the data must be viewed as very preliminary.

What are the implications; or is it too early for there to be any?

“This data may help to instruct a key area for research, which needs to be prioritised, but it is not sufficient to inform clinical practice.  Patients and doctors should continue to follow national and international guidance on the treatment of hypertension whilst further research is undertaken.”

Prof Ian Hall, Professor of Molecular Medicine, and Director of the Nottingham Biomedical Research Centre, University of Nottingham, said:

“This study provides preliminary results suggesting that patients with high blood pressure taking two commonly used types of blood pressure treatment do not appear to be at increased risk of severe COVID19 disease.  This is reassuring as it has been suggested that people taking ACE inhibitors or Angiotensin II receptor antagonists, two widely used groups of drugs used to lower blood pressure, might have worse outcomes; this is because the virus uses a receptor called ACE2 to enter the cell, and there is a theoretical risk that patients taking these drugs might express more ACE2 in the airway and therefore be at increased risk from the virus.

“The study does have some weaknesses; it is based on a retrospective review of cases, and it is difficult in a relatively small study to control sufficiently for other risk factors.  However, overall the message is helpful.  Indeed, if anything, patients taking these drugs appeared to do somewhat better, although the differences in the most relevant clinical outcomes were not statistically significant.

“Ensuring patients with high blood pressure continue to take their medication is obviously important, as poor blood pressure control is associated with severe complications such as stroke and heart attacks.  Current advice, which is to stay on these drugs rather than change to other drugs, should continue to stand.”

Prof Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases, University of Nottingham, said:

“This is an interesting and important piece of work.  One of the surprises was that hypertension was identified as a risk factor for severe COVID-19.  The COVID-19 virus uses the ACE-2 receptor to enter the cell and these receptors are upregulated but the ACEI and ARB drugs commonly used in hypertension, hence a possible explanation.  This paper suggests that is not the case but given the large numbers of people taking these drugs amongst age groups most severely affected by COVID-19 it is important that this work is replicated.  This work has not been formally peer reviewed the method used are standard for this type of study.”

Preprint (not a paper): ‘Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension’ by Guang Yang et al. is on medRxiv.  This work is not peer-reviewed.

https://www.medrxiv.org/content/10.1101/2020.03.31.20038935v1

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19/

Declared interests

Prof Stephen Evans: “I have no financial conflicts, but I am involved advising colleagues who are planning a study to attempt to answer these questions, so I have thought about some of the key issues.”

None received.