Positive association of angiotensin II receptor blockers, not angiotensin-converting enzyme inhibitors, with an increased vulnerability to SARS-CoV-2 infection in patients hospitalized for suspected COVID-19 pneumonia

Georges, Jean; Gilles, Floriane; Cochet, H.; Bertrand, A.; Tournemire, Marie de; Monguillon, V.; Pasqualini, M.; Prevot, A.; Roger, Guillaume; Saba, Joseph; Soltani, J.; Koukabi-Fradelizi, M.; Beressi, J.P.; Laureana, Cécile; Prost, Jean François; Livarek, B.

doi:10.1371/journal.pone.0244349

Cited by 6 publications

(2 citation statements)

References 24 publications

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“…After removing irrelevant items based on the title and abstract, 141 studies were deemed for full-text reading. A total of 49 numbers of articles were used in quantitative analysis [ 12 , 21 – 69 ]. The reason for article inclusion and exclusion is shown in the PRISMA flow (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Safety and Efficacy of Renin–Angiotensin–Aldosterone System Inhibitors in COVID-19 Population

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Mukuntharaj

Zghouzi

et al. 2021

High Blood Press Cardiovasc Prev

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Introduction The safety of renin–angiotensin–aldosterone system inhibitors (RAASi) among COVID-19 patients has been controversial since the onset of the pandemic. Methods Digital databases were queried to study the safety of RAASi in COVID-19. The primary outcome of interest was mortality. The secondary outcome was seropositivity improvement/viral clearance, clinical manifestation progression, and progression to intensive care units. A random-effect model was used to compute an unadjusted odds ratio (OR). Results A total of 49 observational studies were included in the analysis consisting of 83,269 COVID-19 patients (RAASi n = 34,691; non-RAASi n = 48,578). The mean age of the sample was 64, and 56% were males. We found that RAASi was associated with similar mortality outcomes as compared to non-RAASi groups (OR 1.07; 95% CI 0.99–1.15; p > 0.05). RAASi was associated with seropositivity improvement including negative RT-PCR or antibodies, (OR 0.96; 95% CI 0.93–0.99; p < 0.05). There was no association between RAASi versus control with progression to ICU admission (OR 0.99; 95% CI 0.79–1.23; p > 0.05) or higher odds of worsening of clinical manifestations (OR 1.04; 95% CI 0.97–1.11; p > 0.05). Metaregression analysis did not change our outcomes for effect modifiers including age, sex, comorbidities, RAASi type, or study type on outcomes. Conclusions COVID-19 is not a contraindication to hold or discontinue RAASi as they are not associated with higher mortality or worsening symptoms. Continuation of RAASi might be associated with favorable outcomes in COVID-19, including seropositivity/viral clearance. Supplementary Information The online version contains supplementary material available at 10.1007/s40292-021-00462-w.

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Section: Resultsmentioning

confidence: 99%

“…A total of 49 studies with 83,269 of COVID-19 patients (RAASi n = 34,691; non-RAASi n = 48,578) were included in the study [ 12 , 21 – 69 ]. The included study population had confirmed COVID-19 diagnosis by nasopharyngeal reverse transcriptase-polymerase chain reaction (RT-PCR).…”

Section: Resultsmentioning

confidence: 99%

Safety and Efficacy of Renin–Angiotensin–Aldosterone System Inhibitors in COVID-19 Population

Sattar

Mukuntharaj

Zghouzi

et al. 2021

High Blood Press Cardiovasc Prev

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Renin‐Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID‐19

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Lampa

Gustafsson

et al. 2021

JAHA

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Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin‐angiotensin aldosterone system (RAAS) inhibitor use and COVID‐19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID‐19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine‐learning‐derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID‐19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74–1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID‐19 (HR, 0.92; 95% CI, 0.70–1.22), and 64 died with COVID‐19 (HR, 1.22; 95% CI, 0.68–2.19). The severity of COVID‐19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89–1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID‐19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID‐19 pandemic.

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Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

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Taylor

Lampa

et al. 2022

JAHA

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Background Renin‐angiotensin aldosterone system (RAAS) inhibitor—COVID‐19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID‐19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor—COVID‐19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID‐19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin‐converting enzyme inhibitors or angiotensin II type‐I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed‐effects meta‐analyses, only from studies without critical risk of bias that assessed severe COVID‐19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta‐analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin‐converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66–0.87; P <0.001; angiotensin II type‐I receptor blockers: HR, 0.86; 95% CI, 0.77–0.97; P =0.015) and intubation or death (angiotensin‐converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48–0.85; P =0.002; angiotensin II type‐I receptor blockers: HR, 0.74; 95% CI, 0.58–0.95; P =0.019) with COVID‐19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID‐19 research, raising an important question: Were research methods and/or peer‐review processes temporarily weakened during the surge of COVID‐19 research or is this lack of rigor a systemic problem that also exists outside pandemic‐based research? Registration URL: www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42021237859.

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Positive association of angiotensin II receptor blockers, not angiotensin-converting enzyme inhibitors, with an increased vulnerability to SARS-CoV-2 infection in patients hospitalized for suspected COVID-19 pneumonia

Cited by 6 publications

References 24 publications

Safety and Efficacy of Renin–Angiotensin–Aldosterone System Inhibitors in COVID-19 Population

Safety and Efficacy of Renin–Angiotensin–Aldosterone System Inhibitors in COVID-19 Population

Renin‐Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID‐19

Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

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