Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France

Oussalah, Abderrahim; Gleye, Stanislas; Urmes, Isabelle Clerc; Laugel, Elodie; Callet, Jonas; Barbé, Françoise; Orlowski, Sophie; Malaplate, Catherine; Aimone-Gastin, I.; Caillierez, Beatrice Maatem; Merten, Marc; Jeannesson, Élise; Kormann, Raphaël; Olivier, Jean‐Luc; Rodriguez-Guéant, Rosa-Maria; Namour, Farès; Bévilacqua, S.; Losser, Marie-Reine; Lévy, Bruno; Kimmoun, Antoine; Gibot, Sébastien; Thilly, Nathalie; Frimat, Luc; Schvoerer, Évelyne; Guéant, Jean‐Louis

doi:10.1093/cid/ciaa677

Cited by 59 publications

(62 citation statements)

References 37 publications

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“…Some studies did not find any relationship between the use of ACE-I or ARB and the development of AKI 31,32 . Contrary to these results, Oussalah et al reported a harmful effect of long-term ACE-I or ARB use on the renal function and further interaction with the occurrence of AKI and ARDS in 149 patients with severe COVID-19 33 . Our study highlighted the possible association between ACE-I or ARB use and a significant increase in both ARDS and AKI.…”

Section: Discussionmentioning

confidence: 82%

Adverse impact of renin–angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

Lim

Cho

Jeon

et al. 2020

Sci Rep

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The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10–4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02–6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15–8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.

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Section: Discussionmentioning

confidence: 82%

Adverse impact of renin–angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

Lim

Cho

Jeon

et al. 2020

Sci Rep

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“…The evidence for the safety of other ACE2-raising drugs, used alone or in combination, is sparse but the majority of the studies discussed herein suggested that these drugs are not associated with adverse outcomes with exception of one study indicating increased risk of AKI in patients receiving ACEI/ARBs in severe COVID-19 disease [117]. Although the majority of clinical studies examining outcomes on COVID-19 patients have reported results for combined use of ACEIs and ARBs, it should be noted that these two drug classes have divergent cardiovascular effects and outcomes in patients [152], and perhaps future studies should aim to report results for ACEIs and ARBs separately.…”

Section: Resultsmentioning

confidence: 95%

“…A large body of evidence from clinical observational studies reported thus far, as well as our recalculation of meta-analysis data on all-cause mortality, supports continued use of ACEIs/ARBs in COVID-19 patients. Although these drugs generally appear to be clinically safe, their chronic use in severe COVID-19 patients might increase the risk of acute renal injury [117]. Evidence also exists for the beneficial effects of ACEIs/ARBs in some sub-populations of COVID-19 patients such as in lowering risk of mortality in hypertensive patients or decreasing risk of hospitalisation for COVID-19 patients with diabetes.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, evidence from the literature reviewed above supports the current guidelines issued by several societies including the recent joint statement of the British Cardiovascular Society together with the British Society for Heart Failure (https://www.britishcardiovascularsociety.org/news/ ACEi-or-ARB-and-COVID-19) that COVID-19 patients can continue with their existing ACEI/ARB therapies. Based on a recent report [117], we suggest that patients with severe COVID-19 on ACEIs or ARBS should be monitored for development of renal dysfunction and AKI. However, for definitive clarity there is still a need for large scale, well-conducted randomised clinical trials as well mechanistic studies investigating the safety of the many ACE2-raising drugs that are routinely used in the clinic in COVID-19 patients.…”

Section: Resultsmentioning

confidence: 99%

“…The importance of the impact of ACEI/ARB pharmacotherapy and stage of COVID-19 disease was highlighted recently in a study from France. In a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19 [117], chronic use of ACEIs/ARBs in 44 patients was associated with an increased risk of developing acute renal injury (AKI) stage !1 (OR, 3.28, 95% CI, 2.17-4.94). Despite the small number of patients, the authors showed that daily dose of ACEIs/ARBs was independently associated with increased risk of elevated kidney markers, such as urea nitrogen >0.52 g/L (OR, 1.26 [95% CI, 1.13-1.41] with an increased risk of þ25 to þ31% per each 10 mg increment of the lisinopril-dose equivalent.…”

Section: Meta-analyses Of Clinical Studies Of Covid-19 Patients Receimentioning

confidence: 99%

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Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety

Akhtar

Benter

Danjuma

et al. 2020

Journal of Drug Targeting

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The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes-and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.

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Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

et al. 2021

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Key Points Question Is the receipt of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) associated with worse clinical outcomes among patients with COVID-19? Findings In this systematic review and meta-analysis of 52 studies that evaluated clinical outcomes among 101 949 total patients with COVID-19 who did and did not receive ACEIs or ARBs, a significantly lower risk of multivariable-adjusted mortality and severe adverse events was found among patients who received ACEIs or ARBs compared with patients who did not. A subgroup analysis of patients with hypertension indicated significant decreases in mortality and severe adverse events among patients receiving ACEIs or ARBs in both unadjusted and adjusted analyses. Meaning The study’s findings suggest that ACEIs and ARBs may be associated with protective benefits for patients with COVID-19 and that patients may continue receiving ACEIs and ARBs for the treatment of any condition without an increased risk of worse outcomes unless specifically advised to avoid them by treating clinicians.

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Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France

Cited by 59 publications

References 37 publications

Adverse impact of renin–angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

Adverse impact of renin–angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety

Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

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