Renin-Angiotensin System Inhibitors and COVID-19: a Systematic Review and Meta-Analysis. Evidence for Significant Geographical Disparities

Patoulias, Dimitrios; Katsimardou, Alexandra; Stavropoulos, Konstantinos; Imprialos, Κonstantinos; Kalogirou, Maria‐Styliani; Doumas, Michael

doi:10.1007/s11906-020-01101-w

Cited by 42 publications

(53 citation statements)

References 57 publications

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“…Accordingly, one must adjust for indication bias in patients who are on or not on ARBs or ACE inhibitors. Some prior meta-analyses and studies found that use of ARBs and/or ACE inhibitors were not associated with altered mortality (10)(11)(12)(13)(14)(15)(16), while one meta-analysis found that ACE inhibitors but not ARBs were associated with decreased COVID-19 mortality or critical illness (17) and others found that the use of ARBs or ACE inhibitors was associated with decreased mortality overall (18,19) or in patients with cardiovascular disease (20) or hypertension (21)(22)(23)(24)(25). The reason for these conflicting results could partly be due to methodological differences.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors

et al. 2021

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BACKGROUND Angiotensin receptor blockers (ARBs) and/or angiotensin converting enzyme (ACE) inhibitors could alter mortality of COVID-19, but existing meta-analyses which combined crude and adjusted results may be confounded by comorbidities being more common in ARBs/ACE inhibitors users. METHODS We searched PubMed/MEDLINE/Embase for cohort studies and meta-analysis reporting mortality by pre-existing ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex and prevalence of cardiovascular disease, hypertension, diabetes mellitus and chronic kidney disease between users and non-users of ARBs/ACE inhibitors at the study-level during data synthesis. RESULTS In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus and chronic kidney disease. ARBs/ACE inhibitors use was associated with significantly lower mortality after controlling for potential confounding factors (OR 0.77 (95% CI: 0.62, 0.96)). In contrast, meta-analysis of ARBs/ACE inhibitors use was not significantly associated with mortality when all studies were combined with no confounder adjustment performed (0.87 (95% CI: 0.71, 1.08)). CONCLUSIONS ARBs/ACE inhibitors use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality of COVID-19 because of indication bias.

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Section: Introductionmentioning

confidence: 99%

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors

et al. 2021

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“…In another meta-analysis where the relationship of the use of RAASBs with the probability of COVID-19 is stated, geographical differences are evidenced, detecting that the use of RAASBs is generally associated with a better prognosis only in studies carried out in Asian countries (OR.0.37; 95% CI: 0.16-0.89) whereas, in those carried out in North America, it is commonly associated with an even more significant increase in ICU admissions (OR: 1.75; 95% CI: 1.37-2.23) and in those carried out in Europe it is related with a higher death probability (OR: 1.68; 95% CI: 1.05-2.70). The authors note that ACEIs would be mainly protective and conversely, ARBs would be associated with an increased risk of death [32]. In a different sense are the findings of the meta-analyses of Megaly et al [33] and Chan et al [34].…”

Section: Discussionmentioning

confidence: 99%

The Age Again in The Eye of The Covid-19 Storm: Evidence-Based Decision Making.

Martín

Jurado

Abad-Molina

et al. 2021

Preprint

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Background: One hundred million of contagions, more than 2 million deaths and less than one year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. Results: Concerning the characteristics of lockdown series, mild cases accounted for 14.4%, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age >60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. Age, lymphocyte count and LDH had similar distributions at both moments. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. Conclusion: Age, sex and dyslipidaemia together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown could affect the homogeneity of the data and the robustness of the results.

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“…While the pandemic is rapidly evolving, the neutral effect of RASi exposure on mortality is increasingly recognized, although some disparities exist. Patoulias et al [ 15 ] showed that, although the use of RASi does not increase the odds for SARS-CoV-2-related death in a global scenario (OR = 1.06, 95% CI 0.77–1.47, I 2 = 83%), it increases the odds for death in Europe by 68% (OR = 1.68, 95% CI 1.05–2.70, I 2 = 82%), while decreasing it in Asia by 38% (OR = 0.62, 95% CI 0.39–0.99, I 2 = 0%). Others have come to the same nonsignificant results in a global perspective, but no subgroup analysis by region was made [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

Gaspar

Parreira

Meireles

et al. 2021

International Journal of Hypertension

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Background. Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. Objectives. We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. Methods. Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. Results. From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66–2.31, p = 0.500 ), ARDS/ALI development (OR 1.12, 95% CI 0.67–1.86, p = 0.676 ), ICU admission (OR 1.11, 95% CI 0.67–1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58–1.84, p = 0.917 ) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11–17.21, p = 0.035 ) and ARDS/ALI development (OR 4.33, 95% CI 1.49–12.6, p = 0.007 ), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission ( p = 0.018 ). IL-6 levels were significantly higher in those patients whose RASi were stopped ( p = 0.024 ). Conclusion. Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

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Renin-Angiotensin System Inhibitors and COVID-19: a Systematic Review and Meta-Analysis. Evidence for Significant Geographical Disparities

Cited by 42 publications

References 57 publications

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors

Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors

The Age Again in The Eye of The Covid-19 Storm: Evidence-Based Decision Making.

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

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