Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and COVID-19-related outcomes: A patient-level analysis of the PCORnet blood pressure control lab

Smith, Steven M.; Desai, Raj; Walsh, Marta; Nilles, Ester Kim; Shaw, Katie; Smith, Molly Housley; Chamberlain, Alanna M.; Derington, Catherine G.; Bress, Adam P.; Chuang, Cynthia H.; Ford, Daniel E.; Taylor, Bradley; Chandaka, Sravani; Patel, Lav P.; McClay, James C.; Priest, Elisa L.; Fuloria, Jyotsna; Doshi, Kruti; Ahmad, Faraz; Viera, Anthony J.; Faulkner, Madelaine; O’Brien, Emily C.; Pletcher, Mark J.; Cooper‐DeHoff, Rhonda M.

doi:10.1016/j.ahjo.2022.100112

Cited by 5 publications

(2 citation statements)

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“…Our findings would support the assumption that the up-regulation of angiotensin-converting enzyme (ACE)-2, a carboxypeptidase that cleaves angiotensin II into angiotensin- ( 1 – 7 , 56 , 57 ), induced by both ACEIs ( 58 – 60 ) and ARBs ( 61 ), could be potentially useful in the clinical course of SARS-CoV-2-infected patients, due to the cardiovascular protection elicited by the increased activity of angiotensin ( 1 – 7 ), thereby attenuating angiotensin II effects on vasoconstriction and sodium retention ( 57 , 59 ). Therefore, our results are in alignment with previous studies that demonstrated a significantly lower mortality rate in hospitalized COVID-19 patients treated with ACEI/ARB therapy ( 62 – 67 ).…”

Section: Discussionsupporting

confidence: 92%

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period

et al. 2022

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PurposeTo investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period.MethodsAll consecutive hospitalized laboratory‐confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality.Results74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%.ConclusionsHigh comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

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Section: Discussionsupporting

confidence: 92%

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period

et al. 2022

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“…[11] Finally, Smith et al have recently reported on a very large cohort of COVID-19-infected patients that ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19. [12] However, regarding the impact of RAAS blockers in the population of CKD patients having SARS-CoV-2 infection, there are no specific data. This is the reason why we conducted a prospective observational study in Bulgarian COVID-19-infected patients with or without CKD, in which we assessed whether maintenance RAAS blocker therapy has an impact on COVID-19 and its complications.…”

Section: Introductionmentioning

confidence: 99%

Renin-angiotensin-aldosterone system blockers in Bulgarian COVID-19 patients with or without chronic kidney disease

et al. 2022

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When angiotensin-converting enzyme inhibitor/angiotensin receptor blocker-treated patients present with SARS-CoV-2 infection there is a debate to know whether renin-angiotensin-aldosterone (RAAS) blockers should be stopped or not. We conducted a prospective observational study in Bulgarian COVID-19-infected patients with or without chronic kidney disease (CKD) to assess whether maintenance RAAS blocker therapy has an impact on SARS-CoV-2 infection and its complications. We included 120 in-patient COVID-19 subjects, of whom 70 had CKD and 50 had normal renal function. A total of 30% of the patients (total number of 36 patients, 21 females) were receiving RAAS therapy at admission and it was maintained throughout hospitalization. The overall mortality was 19.2% (23 patients); there was no significant difference across the 2 groups (P-value = .21), except in RAAS blockers-treated hypertensive patients who had a significantly lower mortality as compared to non-RAAS-blockers-treated hypertensive patients (P = .04). Regarding subsequent intensive-care unit admission, there were 50% less patients in the RAAS group (4 out of 36, i.e., 11%) as compared to 19 out of 84 from the non-RAAS group, that is, 22.6% (P = .29). Overall, 37 patients developed acute kidney injury (any stage by KDIGO); of them 14 (37.8%) were receiving RAAS blockers. Acute kidney injury was not significantly associated with the use of RAAS blockers (P-value = .28). Likewise, both in non-CKD and in CKD patients the use of RAAS blockers did not have an impact on renal function recovery after SARS-CoV-2 infection. Finally, regarding RAAS blockers and the biological parameters outcome only D-dimers were significantly lower at the follow-up as compared to that in non-RAAS blocker treated patients. RAAS blockers benefited patients with hypertension by lowering mortality rate. Other than that, RAAS blocker therapy continuation during SARS-CoV-2 infection in CKD and non-CKD patients had no significant impact upon major outcomes.

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Association of outpatient use of renin–angiotensin–aldosterone system blockers on outcomes of acute respiratory illness during the COVID-19 pandemic: a cohort study

et al. 2022

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ObjectivesEvaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19.DesignRetrospective cohort.SettingThe USA; 2017–2018 influenza season, 2018–2019 influenza season, and 2019–2020 influenza/COVID-19 season.ParticipantsPeople with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI.Main outcome measuresChange in hospital admission, intensive care unit (ICU) or coronary care unit (CCU), acute respiratory distress (ARD), ARD syndrome (ARDS) and all-cause mortality, comparing COVID-19 to pre-COVID-19 influenza seasons.ResultsThe cohort included 1 059 474 episodes of AVRI (653 797 filled an ACEi or ARB, and 405 677 other HTN medications). 58.6% were women and 72.9% with age ≥65. The ACEi/ARB cohort saw a larger increase in risk in the COVID-19 influenza season than the other HTN medication cohort for four out of five outcomes, with an additional 1.5 percentage point (pp) increase in risk of an inpatient stay (95% CI 1.2 to 1.9 pp) and of ICU/CCU use (95% CI 0.3 to 2.7 pp) as well as a 0.7 pp (0.1 to 1.2 pp) additional increase in risk of ARD and 0.9 pp (0.4 to 1.3 pp) additional increase in risk of ARDS. There was no statistically significant difference in the absolute risk of death (−0.2 pp, 95% CI −0.4 to 0.1 pp). However, the relative risk of death in 2019/2020 versus 2017/2018 for the ACEi/ARB group was larger (1.40 (1.36 to 1.44)) than for the other HTN medication cohort (1.24 (1.21 to 1.28)).ConclusionsPeople with AVRI using ACEi/ARBs for HTN had a greater increase in poor outcomes during the COVID-19 pandemic than those using other medications to treat HTN. The small absolute magnitude of the differences likely does not support changes in clinical practice.

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Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and COVID-19-related outcomes: A patient-level analysis of the PCORnet blood pressure control lab

Cited by 5 publications

References 26 publications

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period

Renin-angiotensin-aldosterone system blockers in Bulgarian COVID-19 patients with or without chronic kidney disease

Association of outpatient use of renin–angiotensin–aldosterone system blockers on outcomes of acute respiratory illness during the COVID-19 pandemic: a cohort study

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