{"doi":"10.1093/ajh/hpaa177","title":"Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and COVID-19: Demonstrating the Actionability of Real-World Evidence","abstract":"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used by many millions of people1 for highly prevalent conditions including hypertension, heart failure, and diabetes. It was therefore quite concerning when mechanistic considerations regarding the role of angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of SARS-CoV-22 led to the hypotheses that these widely used, lifesaving drugs might both increase the risk of developing COVID-19 and worsen outcomes in people who developed COVID-19. These hypotheses were especially concerning because the aforementioned therapeutic indications for using ACEIs and ARBs themselves are among the most prevalent comorbidities in patients who develop COVID-19, and are associated with worse outcomes of COVID-19.3,4 Based on these mechanistic considerations, some authors went so far as to recommend that ACEIs and ARBs be discontinued in patients with active COVID-19 infection, and that their discontinuation be considered in some people who are at high risk for developing COVID-19.5,6 It is therefore reassuring that the recent population-based cohort study conducted by Dublin et al.7 found that ACEIs and ARBs do not appear to increase the risk of developing COVID-19 or to increase the risk of hospitalization in those who develop COVID-19, and that there is no dose–response relationship between ACEI/ARB use and risk of developing COVID-19 or of being hospitalized once a person has developed COVID-19. The study by Dublin et al. has numerous strengths that bolster the confidence that we can have in its conclusions. These strengths include a methodologically rigorous, clinically informed design that adjusted for a broad set of potential confounders, including diseases, dispensed prescription drugs, and several potentially important factors that are often unavailable in administrative databases such as race/ethnicity, tobacco use, and body mass index. Indeed, the study demonstrated the importance of adjusting for such factors, since ACEI/ARB use was associated with adverse outcomes in unadjusted but not in adjusted analyses, similar to prior studies evaluating this question.8 This suggests that a less rigorous study that controlled for a narrower set of confounders might have yielded spurious associations between ACEIs/ARBs and adverse outcomes. The study was also large enough to produce reasonably narrow 95% confidence intervals that suggest that the results are statistically incompatible with even moderately strong associations. The broad inclusion criteria for the primary analyses helped to reduce the risk for selection and collider bias. Secondary analyses were restricted to patients with indications for ACEI/ARB use to help to address confounding by indication. Finally, the study examined dose–response relationships and associations with comparator antihypertensive medications (examined as control exposures) that would have helped to contextualize any positive associations that may have emerged between ACEIs/ARBs and adverse outcomes. The results of Dublin et al.’s paper agree with and extend those of prior studies, conducted in Europe, that found no association between ACEI/ARB use and the development and severity of COVID-19.9–11 Prior observational studies evaluating the association between ACEI/ARB use and the development and severity of COVID-19 had several potential weaknesses such as collider bias, the potential for misclassification of ACEI/ARB use in the absence of dispensing data, and lack of information on ACEI/ARB dose. In addressing several of the limitations of prior studies, Dublin et al.’s findings strengthen the existing evidence supporting current recommendations12 to continue indicated ACEI/ARB therapy during the pandemic, even in people who develop COVID-19. There are potential physiologic explanations for the lack of association of ACEI/ARB use with development and severity of COVID-19 observed in the current study. Early in the","journal":"American Journal of Hypertension","year":2020,"id":108777,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228812,"name":"Jordana B. Cohen","orcid":"0000-0003-4649-079X","position":1,"is_corresponding":false},{"id":356700,"name":"Sean Hennessy","orcid":"0000-0003-4726-9413","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-18T23:12:46.854423Z","pmid":"33156920","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}