Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality

Abstract

IMPORTANCE It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.OBJECTIVE To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSTo examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.EXPOSURES ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. MAIN OUTCOMES AND MEASURESIn the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. RESULTSIn the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age-and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). CONCLUSIONS AND RELEVANCEPrior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

First Wave of COVID-19 Hospital Admissions in Denmark: A Nationwide Population-Based Cohort Study

“…By early April 2020, a few pharmacological interventions were available mostly within the frame of clinical trials [28], which, alongside with improved clinical management, could have had an impact on our outcome estimates over time. In comparison to previous studies from Denmark [5][6][7] we found a higher mortality. However, we report outcomes in a selected group of patients namely those in need of hospitalisation and therefore presenting with a more severe clinical course.…”

“…The rst case in Denmark was diagnosed on February 27th, 2020, and during the rst month, the number of laboratory-con rmed cases rose to more than 3,000; 500 patients were hospitalised, of which 30% required admission to an intensive care unit (ICU) and 5% died Despite variations reported across countries, emerging evidence consistently indicates that older men with multiple comorbidities have poorer COVID-19-related outcomes [2][3][4]. To date, studies from Denmark focusing on the overall epidemiological characteristics during the early phase of the epidemic (until May 2020) [5,6] and the association with several cardiovascular outcomes have been made publicly available [7]. From these early reports, COVID-19 related mortality in Denmark have been described to vary between 9.3-16.6% and rates of ICU admission between 12.9-17.8% depending on the speci c groups of patients studied [5,7].…”

“…To date, studies from Denmark focusing on the overall epidemiological characteristics during the early phase of the epidemic (until May 2020) [5,6] and the association with several cardiovascular outcomes have been made publicly available [7]. From these early reports, COVID-19 related mortality in Denmark have been described to vary between 9.3-16.6% and rates of ICU admission between 12.9-17.8% depending on the speci c groups of patients studied [5,7].…”

Curative anticoagulation prevents endothelial lesion in COVID‐19 patients

“…However, the main scientific societies of cardiology and more specifically of hypertension took the position not to withdraw ACEi or ARB therapy in COVID‐19. Hence, the Council on Hypertension of the European Society of Cardiology recommended that "patients should continue treatment with their usual anti‐hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEIs or ARBs should be discontinued because of the COVID‐19 infection.” 33 Indeed, recent studies did not find any association between ACEi or ARBs therapy and worsening in COVID‐19 patients 34 …”

Fighting COVID-19 spread among nursing home residents even in absence of molecular diagnosis: a retrospective cohort study.

“…The lower prevalence of ACE inhibitor intake among COVID-19 seropositive patients does not support the hypothesis that these molecules could make patients more susceptible to SARS-Cov2 infection. However, literature data still remains controversial [25,26].…”