Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors

Golpe, Rafael; Pérez-de-Llano, Luis; Dacal, David; Guerrero-Sande, Héctor; Pombo-Vide, Beatriz; Ventura-Valcárcel, Pablo

doi:10.1016/j.medcli.2020.06.013

Cited by 20 publications

(16 citation statements)

References 10 publications

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“…In the first moment, viral dynamics and clinical severity were postulated to be related to these drugs, but this has not been confirmed in subsequent studies. 19 In our study, despite its small power to answer this question, we did not find any relation between ACEI and ARB intake and VD.…”

Section: Discussioncontrasting

confidence: 65%

Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity

et al. 2020

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BackgroundGlobal pandemic SARS-CoV-2 causes a prothrombotic state without fully elucidated effects. This study aims to analyse and quantify the possible retinal microvascular abnormalities.Materials and methodsCase–control study. Patients between 18 and 55 years old with PCR-confirmed SARS-CoV-2 infection within the last 3 months were included. Risk stratification: group 1—mild disease (asymptomatic/paucisymptomatic); group 2—moderate disease (required hospital admission with no acute respiratory distress) and group 3—severe disease (subjects who developed an acute respiratory distress were admitted in the intensive care unit and presented interleukin 6 values above 40 pg/mL). Age-matched volunteers with negative serology tests were enrolled to control group. A colour photograph, an optical coherence tomography (OCT) and an angiography using OCT centred on the fovea were performed.ResultsControl group included 27 subjects: group 1 included 24 patients, group 2 consisted of 24 patients and 21 participants were recruited for group 3. There were no funduscopic lesions, neither in the colour images nor in the structural OCT. Fovea-centred vascular density (VD) was reduced in group 2 and group 3 compared with group 1 and control group (control group vs group 2; 16.92 vs 13.37; p=0.009) (control group vs group 3; 16.92 vs .13.63; p=0.026) (group 1 vs group 2; 17.16 vs 13.37; p=0.006) (group 1 vs group 3; 17.16 vs 13.63 p=0.017).ConclusionPatients with moderate and severe SARS-CoV-2 pneumonia had decreased central retinal VD as compared with that of asymptomatic/paucisymptomatic cases or control subjects.

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Section: Discussioncontrasting

confidence: 65%

Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity

et al. 2020

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“…Most prior studies have been limited to examining severity of disease among patients with COVID-19 and have generally found either no change or a reduction in risk of adverse outcomes among ACEI/ARB users [ 6 , 8 , 10 , 15 , 19 ]. Studies among patients with hypertension, patients tested for COVID-19 or the general population have also found no association or a protective association between ACEI/ARB use and COVID-19 test positivity, hospitalization or mortality [ 5 – 7 , 9 , 11 , 14 ]. However, these studies have been unable to adjust for exposure to SARS-CoV-2, a key potential confounder, Furthermore, studies of hospitalization or mortality from COVID-19 are unable to differentiate between associations with the risk of transmission and associations with the severity of disease after transmission.…”

Section: Discussionmentioning

confidence: 99%

“…Use of medications that affect angiotensin converting enzymes (ACE) has received particular attention as a potential risk factor for COVID-19 infection [5][6][7][8][9][10][11][12][13][14][15]. Angiotensin converting enzyme 2 (ACE2) plays a central role in the entry of the SARS-CoV-2 virus into human cells [16,17].…”

Section: Introductionmentioning

confidence: 99%

Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers associated with lower risk of COVID-19 in household contacts

et al. 2021

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Background Use of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been hypothesized to affect COVID-19 risk. Objective To examine the association between use of ACEI/ARB and household transmission of COVID-19. Methods We conducted a modified cohort study of household contacts of patients who tested positive for COVID-19 between March 4 and May 17, 2020 in a large Northeast US health system. Household members were identified by geocoding and full address matching with exclusion of addresses with >10 matched residents or known congregate living functions. Medication use, clinical conditions and sociodemographic characteristics were obtained from electronic medical record (EMR) data on cohort entry. Cohort members were followed for at least one month after exposure to determine who tested positive for SARS-CoV-2. Mixed effects logistic regression and propensity score analyses were used to assess adjusted associations between medication use and testing positive. Results 1,499 of the 9,101 household contacts were taking an ACEI or an ARB. Probability of COVID-19 diagnosis during the study period was slightly higher among ACEI/ARB users in unadjusted analyses. However, ACEI/ARB users were older and more likely to have clinical comorbidities so that use of ACEI/ARB was associated with a decreased risk of being diagnosed with COVID-19 in mixed effect models (OR 0.60, 95% CI 0.44–0.81) or propensity score analyses (predicted probability 18.6% in ACEI/ARB users vs. 24.5% in non-users, p = 0.03). These associations were similar within age and comorbidity subgroups, including patients with documented hypertension, diabetes or cardiovascular disease, as well as when including other medications in the models. Conclusions In this observational study of household transmission, use of ACEIs or ARBs was associated with a decreased risk of being diagnosed with COVID-19. While causality cannot be inferred from these observational data, our results support current recommendations to continue ACEI/ARB in individuals at risk of COVID-19 exposure.

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“…Among the seven studies, four involved US patients, three enrolled Europeans while none was from China. (8,9,14,18,25,32,33) Country specific subgroup and sensitivity analysis showed a nearly 4 times higher risk of hospitalisation in US patients (pooled OR 3.87 (1.21-12.34), I 2 =97%) while no such risk was evident in Europeans (pooled OR 1.17 (0.20-6.82), I 2 =95%) ( Supplementary Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

RAAS blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis

Kaur

Chakrabarti

Patel

2020

Preprint

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Background: Coronavirus disease 2019 (COVID-19) has evolved as a global crisis with high mortality seen in elderly and people with cardiometabolic diseases. The use of renin angiotensin aldosterone system (RAAS) blockers in these patients is known to enhance the expression of ACE-2, the chief binding receptor of SARS-CoV-2 and may potentially enhance infectivity. Objective: To provide a pooled estimate of the effect of RAAS blocker usage on COVID-19 outcomes. Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Google Scholar) and preprint (using bioRxiv and medRxiv) studies of interest. The last search was conducted on 9th July 2020. Study Selection: Studies reporting data on RAAS blocker use and COVID-19 mortality and severity were included in the review. Data Extraction and Synthesis: Mortality data and severity data including hospitalization, intensive care unit (ICU) admission, invasive ventilation, steroid use and acute kidney injury (AKI) were recorded. Pooled Odds ratio (OR) estimates were reported with 95% CIs and level of heterogeneity (I2). Main Outcomes and Measures: Odds of mortality in users of RAAS blockers with respect to non-users was the primary outcome. Odds of severity, hospitalization, ICU admission, mechanical ventilation, steroid use, and AKI in users with respect to non-users of RAAS blockers were the secondary outcomes. Results: Of 1348 articles identified, 48 published studies were included in the final analysis, with a total of 26432 patients from 31 studies included in mortality analysis and 20127 patients from 23 studies included in severity analysis. Majority of the studies (41.6%) were from China. No increased risk of mortality (Pooled OR 0.91 (0.65-1.26), I2=89%) or severity (Pooled OR 1.08 (0.79-1.46), I2=88%) was seen with RAAS blockers. The drug class was protective in hypertension (pooled OR 0.63 (0.46-0.86), I2=58%). Severity of COVID-19 outcomes was found to be high for Europeans (Pooled OR 2.08 (1.52-2.85), I2=77%) and US patients (Pooled OR 1.87 (1.62-2.17) in users of RAAS-blockers. A nearly 4 times higher risk of hospitalization, two times higher risk of ICU admission and mechanical ventilation was observed in US patients on RAAS blockers. No net effect on mortality and severity outcomes was seen in Chinese patients. RAAS blocker usage did not have any effect on corticosteroid use and AKI in Chinese patients. Conclusions and Relevance: Use of RAAS blockers is not associated with increased risk of mortality in COVID-19 patients. Reduced mortality is seen in hypertensive patients with COVID-19 and therefore the drugs should be continued in this subset. US and European patients are at higher risk of severe outcomes. Pharmacogenomic differences may explain the ethnicity related variations.

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Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors

Cited by 20 publications

References 10 publications

Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity

Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity

Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers associated with lower risk of COVID-19 in household contacts

RAAS blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis

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