Tag Archives: lisinopril

An Update On ACE2, RAAS and Covid-19: Still No Reason To Stop Or Change Your Blood Pressure Medication

Previously, I wrote a detailed post on concerns that have been raised about certain blood pressure medications potentially  increasing the risk of contracting SARS-CoV-2 or increasing the likelihood of death and serious disease related to the virus.

Millions of patients worldwide with heart failure and hypertension are taking drugs that inhibit pathways in the renal angiotensin aldosterone system termed angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs.)

Lisinopril and ramipril are common ACE inhibitors whereas valsartan, losartan, and irbesartan are common ARBs.

Speculation that these drugs might be contributing to mortality associated with COVID-19 was initiated by a “Rapid Response” published online March 3 by the British Medical Journal in response to an editorial on “preventing a COVID-19 pandemic.” and “Correspondence” to the Lancet published March 7.

Since then I’ve been following this topic closely but nothing has emerged from any new data or new expert analysis to suggest that patients should stop taking ACE inhibitors or ARBs.

Yesterday, an excellent summary of the topic from some of the world’s leading authorities was published in the New England Journal of Medicine entitled “Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19″

It begins with this wonderful sentence: “The renin–angiotensin–aldosterone system (RAAS) is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology.”

The authors outline in detail the possible interactions between ACE2 receptors and SARS CoV-2.

For those not interested in the scientific details in the paper, the Cliff’s Notes version of this article is below. Basically, we have insufficient data to know if patients taking RAAS inhibitors are at higher or lower risk for serious SARS-CoV-2 infection.


KEY POINTS RELATED TO THE INTERPLAY BETWEEN COVID-19 AND THE RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM

  • • ACE2, an enzyme that physiologically counters RAAS activation, is the functional receptor to SARS-CoV-2, the virus responsible for the Covid-19 pandemic
  • • Select preclinical studies have suggested that RAAS inhibitors may increase ACE2 expression, raising concerns regarding their safety in patients with Covid-19
  • • Insufficient data are available to determine whether these observations readily translate to humans, and no studies have evaluated the effects of RAAS inhibitors in Covid-19
  • • Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in Covid-19
  • • Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have heart failure or have had myocardial infarction, may result in clinical instability and adverse health outcomes
  • • Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with Covid-19

So my recommendations (and more importantly the recommendations of every major society or organization which has weighted in on this topic) to patients remain the same: don’t stop your ACE inhibitor or ARB due to concerns about coronavirus.

Skeptically Yours,

-ACP

Coronavirus and ACE Inhibitors: Do Not Stop Taking Your Blood Pressure Medication

Many of my patients with hypertension and/or cardiovascular disease are taking drugs termed angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs.)

Both types of drugs are mainstays in our treatment of hypertension and heart failure.

Lisinopril and ramipril are common ACE inhibitors whereas valsartan, losartan, and irbesartan are common ARBs.

Speculation that these drugs might be contributing to mortality associated with COVID-19 was initiated by a “Rapid Response” published online March 3 by the British Medical Journal in response to an editorial on “preventing a COVID-19 pandemic.” and “Correspondence” to the Lancet published March 7.

I’ve provided the paragraph in which the authors of the Rapid Response raise the question along with their rationale at the end of this post.

Primarily, however, in this post I want to reproduce comments from experts in this area which confirm my observation that the evidence is not sufficient to ask patients to stop these life-saving drugs.

From the European Society of Cardiology yesterday (March 13, 2020):

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 a potential adverse effects of angiotensin converting enzyme inhibitors (ACE-i) 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 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 ACE-i and ARBs.

Because of the social media-related amplification, patients taking these drugs for their high blood pressure and their doctors have become increasingly concerned, and, in some cases, have stopped taking their ACE-I or ARB medications.

This speculation about the safety of ACE-i 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.

The Council on Hypertension of the European Society of Cardiology wish to highlight the lack of any evidencesupporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak.

The Council on Hypertension strongly recommend that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection.

 


 

And from the Science Media Centre:

Prof Tim Chico, Professor of Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Sheffield, said:

“This letter does not report the results of a study; it simply raises a possible question about whether a type of blood pressure and heart disease medication called ACE inhibitors might increase the chances of severe COVID19 infections.  It does not give any evidence that confirms this, simply that it suggests such a relationship should be looked for.

“It is very important that this letter is not interpreted or reported as saying that ACE inhibitors are proven to worsen COVID19 disease.  With more information we will begin to be able to understand whether the relationships between disease severity and existing disease and treatment.

“I strongly advise anyone on heart medications not to stop or change these without discussion with their doctor.  If a patient stops their medication and worsens to the point of requiring admission to hospital at the same time as we are dealing with an increase in COVID19 cases, that would pose the patient a considerable risk and put further strain on the healthcare services.”

 

Prof Peter Sever, Professor of Clinical Pharmacology & Therapeutics, Imperial College London, said:

“There are some questions about whether certain drugs such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers, commonly taken by patients with hypertension, heart failure and diabetes might increase susceptibility to corona virus infection.  On the other hand these drugs could reduce the risk of serious lung disease following infection.

“At the present time we have no evidence as to whether either of these two possibilities are true.

“Patients could be put at risk by stopping these drugs, which are effective treatments for their current condition, without medical supervision, and until further evidence is available should be encouraged to continue their current treatment.”

 

Prof Hugh Montgomery, UCL Professor of Intensive Care Medicine, UCL, said:

“There is no proof yet that the use of ACE inhibitors worsen Coronovirus infection.  There are theoretical reasons, in fact, why they might offer benefit in serious disease.  I would not advocate people ceasing such medication until the evidence has been weighed and clear guidance issued.”

 

Dr Dipender Gill, Specialist Registrar in Clinical Pharmacology and Therapeutics at Imperial College Healthcare NHS Trust, and a Postdoctoral Researcher at Imperial College London, said:

“Evidence is currently lacking and it is too early to make robust conclusions on any link between use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-I receptor blockers with risk or severity of novel coronavirus disease 2019 (COVID-19) infection.  Furthermore, the acute implications of stopping such medications in relation to effects on risk or severity of COVID-19 infection are not known.  Patients should be advised to follow public health guidance rather than alter their medications without proper and informed consultation with their medical doctor.”

 



Let me repeat my main message: Do Not Stop Your Blood Pressure Medication Based On This Speculation.

I will keep monitoring this area and update you as information arises.

 

Skeptically Yours,

-ACP

This article has been updated with additional information as of 3/30/20 with a newer post here.

N.B. It is not unreasonable to raise questions but before making substantial changes in treatment we need more data. Below, the BMJ Rapid Response

The question is, does there exist a connection between the use of these drugs and severe sequela of Covid-19? While the epidemiological association has not been investigated yet, several indicators underline the hypothesis of the link between ACE inhibitors and Covid-19:

On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4].

On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5].

Is a link between these observations possible? Is the expression of ACE2 receptor in the virus targeted cells increased by the use of ACE-inhibitor/angiotensin-receptor blocker and is the patient therefore more at risk for a severe course? We need rapid epidemiological and preclinical studies to clarify this relationship. If this were the case, we might be able to reduce the risk of fatal Covid-19 courses in many patients by temporarily replacing these drugs.