No proof that NSAIDs, ACE inhibitors or angiotensin II blockers can worsen the effects of COVID-19

Various media reports and social media posts originating in France suggest that NSAIDs (particularly ibuprofen) can worsen outcomes in patients with COVID-19. Similar information is circulating about the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II blockers (ARBs). As COVID-19 is a rapidly evolving topic, new data continue to emerge and recommendations could change. However, below is a summary of what several professional organizations are saying about these issues.Nonsteroidal anti-inflammatory drugs The Royal Pharmaceutical Society of Great Britain states that “There is not currently enough information on ibuprofen use and COVID-19 to advise people to stop using NSAIDs. There is currently no published scientific evidence that ibuprofen increases the risk of catching COVID-19 or makes the illness worse. In addition, there is also no conclusive evidence that taking ibuprofen is harmful for other respiratory infections.”(1)The European Medicines Agency (EMA) issued a statement saying that “There is currently no scientific evidence establishing a link between ibuprofen and worsening of COVID‑19. EMA is monitoring the situation closely and will review any new information that becomes available on this issue in the context of the pandemic.”(2)The Health Service Executive (Ireland) is “advising anyone with COVID-19 to continue to take any medication you were already taking, unless you are told not to by a healthcare professional. This includes anti-inflammatories (NSAIDs) such as ibuprofen, naproxen or diclofenac.” The group further stated that “The French Health Minister has made a statement which recommends that paracetamol (acetaminophen) should be used and anti-inflammatory medication avoided in people with COVID-19 in France. This is based on French analysis and is not in line with the analysis and recommendations of the HSE and other EU countries.”(3)The Canadian Pharmacists Association’s statement says “There is insufficient evidence that NSAIDs negatively impact morbidity or mortality of COVID-19. Health Canada continues to recommend both ibuprofen and acetaminophen for treatment of fever due to COVID-19.”(4)The World Health Organization’s official Twitter feed states the following: “WHO is aware of concerns on the use of ibuprofen for the treatment of fever for people with COVID-19. At present, based on currently available information, WHO does not recommend against the use of ibuprofen. We are also consulting with physicians treating the patients and are not aware of reports of any negative effects, beyond the usual ones that limit its use in certain populations. WHO is not aware of published clinical or population-based data on this topic.”(5)NSAIDs Bottom Line: Various experts/groups have issued statements saying that patients taking NSAIDs should continue to do so as there is no good evidence to indicate otherwise. To treat fever in children, either acetaminophen or ibuprofen can be used. However, pharmacists may wish to use a cautious approach and suggest acetaminophen first-line (unless inappropriate or contraindicated) until further information on ibuprofen safety in COVID-19 becomes available.ACEIs and ARBsThe Council on Hypertension of the European Society of Cardiology states that “Based on initial reports from China, and subsequent evidence that arterial hypertension may be associated with increased risk of mortality in hospitalized COVID-19 infected subjects, hypotheses have been put forward to suggest potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). It has been suggested, especially on social media sites, that these commonly used drugs may increase both the risk of infection and the severity of SARS-CoV2 (the virus that causes COVID-19). The concern arises from the observation that, similar to the coronavirus causing SARS, the COVID-19 virus binds to a specific enzyme called ACE2 to infect cells, and ACE2 levels are increased following treatment with ACEIs and ARBs. This speculation about the safety of ACEI or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it. Indeed, there is evidence from studies in animals suggesting that these medications might be rather protective against serious lung complications in patients with COVID-19 infection, but to date there is no data in humans.”(6)“The Council on Hypertension of the European Society of Cardiology wishes to highlight the lack of any evidence supporting harmful effect of ACEIs and ARBs in the context of the pandemic COVID-19 outbreak. The Council strongly recommends that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEIs or ARBs should be discontinued because of the COVID-19 infection.”(6)The International Society of Hypertension (ISH) “completely endorses the content of two recent statements made by the Council on Hypertension of the European Society of Cardiology and the European Society of Hypertension both of which made clear that there is no good evidence to change the use of ACEIs or ARBs for the management of raised blood pressure in the context of avoiding or treating COVID-19 infection.” The ISH also highlights the following critical pieces of information:“There are no clinical data in humans to show that ACEIs or ARBs either improve or worsen susceptibility to COVID-19 infection, nor do they affect the outcomes of those infected.”“In the absence of any such compelling data the ISH strongly recommends that the routine use of ACEIs or ARBs to treat raised blood pressure should continue and should not be influenced by concerns about COVID-19 infection.”(7)Hypertension Canada indicates that “there is no evidence that patients with hypertension or those treated with ARB or ACE inhibitor antihypertensive therapy are at higher risk of adverse outcomes from COVID19 infection. We endorse patients with hypertension to continue with their current blood pressure treatment.”(8)The Renal Association (UK) maintains that “The evidence that these medications increase the risk of death is unconvincing: the reports may simply reflect the fact that people taking the drugs are more likely to have conditions that place them at high risk of severe COVID-19 infection. We therefore advise people taking these medications to continue to take them. If they become unwell such that they need to seek medical help, the doctor may advise stopping the drugs depending on their clinical condition.”(9)A joint statement from the Heart Failure Society of America (HFSA), American College of Cardiology (ACC) and American Heart Association (AHA) asserts that “Currently there are no experimental or clinical data demonstrating beneficial or adverse outcomes with background use of ACEIs, ARBs or other RAAS antagonists in COVID-19 or among COVID-19 patients with a history of cardiovascular disease treated with such agents. The HFSA, ACC, and AHA recommend continuation of RAAS antagonists for those patients who are currently prescribed such agents for indications for which these agents are known to be beneficial, such as heart failure, hypertension, or ischemic heart disease. In the event patients with cardiovascular disease are diagnosed with COVID-19, individualized treatment decisions should be made according to each patient's hemodynamic status and clinical presentation. Therefore, be advised not to add or remove any RAAS-related treatments, beyond actions based on standard clinical practice.”(10) ACEIs and ARBs Bottom Line: Advise patients taking ACEIs or ARBs to continue to take them. There is no clinical or scientific evidence to suggest that treatment with ACEIs or ARBs should be discontinued because of the COVID-19 infection.As COVID-19 is a rapidly evolving topic, I will keep you posted if any new data emerge to change these recommendations.ReferencesAnon. Advice on NSAIDs and COVID-19. Pharm J 2020; March 17, 2020. https://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/advice-on-nsaids-and-covid-19/20207839.article?firstPass=false (accessed March 19, 2020).European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19. Press release March 18, 2020. https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19 (accessed March 19, 2020).Health Service Executive (Ireland). Advice about anti-inflammatory medication and COVID-19. March 16, 2020. https://www.hse.ie/eng/services/news/media/pressrel/advice-about-anti-inflammatory-medication-and-covid-19.html (accessed March 19, 2020).Canadian Pharmacists Association. Use of NSAIDs in patients with COVID-19: what is the evidence? March 17, 2020. https://www.pharmacists.ca/cpha-ca/assets/File/cpha-on-the-issues/Use-of-NSAIDs-in-patients-with-COVID-19-FINAL-EN.pdf (accessed March 19, 2020).World Health Organization. Tweet March 18, 2020. https://twitter.com/who (accessed March 19, 2020).European Society of Cardiology Council on Hypertension. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. March 13, 2020. https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang (accessed March 19, 2020).International Society of Hypertension. A statement from the International Society of Hypertension on COVID-19. https://ish-world.com/news/a/A-statement-from-the-International-Society-of-Hypertension-on-COVID-19/ (accessed March 19, 2020).Hypertension Canada’s statement on: hypertension, ACE-inhibitors and angiotensin receptor blockers and COVID-19. March 13, 2020. https://hypertension.ca/wp-content/uploads/2020/03/2020-30-15-Hypertension-Canada-Statement-on-COVID-19-ACEi-ARB.pdf (accessed March 19, 2020).The Renal Association, UK position statement for patients: novel corona virus infection and the use of blood pressure medications. March 15, 2020. https://renal.org/renal-association-uk-position-statement-patients-novel-corona-virus-infection-use-blood-pressure-medications/ (accessed March 19, 2020).HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. March 17, 2020. https://professional.heart.org/professional/ScienceNews/UCM_505836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-antagonists-in-COVID-19.jsp (accessed March 19, 2020).

No proof that NSAIDs, ACE inhibitors or angiotensin II blockers can worsen the effects of COVID-19

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