Pharmacovigilance in patients with diabetes: A data-driven analysis identifying specific RAS antagonists with adverse pulmonary safety profiles that have implications for COVID-19 morbidity and mortality

Abstract

Objectives: The current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered firstline agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection. Methods: 1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs. Results: Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P ¼ 0.005) as well as ARBs (P ¼ 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. Conclusion: These analyses suggest that pharmacists and clinicians will need to consider the specific medication's adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.

Designed Variants of ACE2-Fc that Decouple Anti-SARS-CoV-2 Activities from Unwanted Cardiovascular Effects

“…Severe cases of SARS-CoV-2 infection frequently have multiorgan involvement(Bosmuller et al, 2020; Menter et al, 2020; Noris, Benigni, & Remuzzi, 2020; Renu, Prasanna, & Valsala Gopalakrishnan, 2020; Zaim, Chong, Sankaranarayanan, & Harky, 2020) that adds difficulty to treatments. In addition, there are concerns that RAAS antagonist medications could be associated with pulmonary adverse drug events in COVID-19 morbidity and mortality(Stafford et al, 2020). In our view, the dual function of investigational drug hrsACE2 to simultaneously act on viral neutralization and RAAS can potentially complicate clinical assessment of therapeutic efficacy.…”

Pulmonary Adverse Event Data in Hypertension with Implications on COVID-19 Morbidity

“…Studies to address the role of these drugs in COVID-19 pathogenesis have primarily focused on broad drug classes rather than individual drugs within a class. However, our recent investigation of renin-angiotensin system (RAS) inhibitors in diabetic patients identified only Captopril as having a unique cluster of multiple pulmonary adverse drug events (ADEs) that could impact the pulmonary symptomology of COVID-19 1 .…”

“…1,21 , we implemented a three-stage approach to curate disparate databases and identified patients with hypertension including pulmonary arterial and intracranial hypertension. First, data mining algorithms were used to identify hypertension datasets and associated post-marketing ADEs for ACEI/ARB drugs that were prevalent among the top reported symptoms in COVID-19 patients.…”

Back to the Normalcy; Is It Possible After the Latest Coronavirus Disease-Covid-19 Attack?

“…The protease is upregulated by androgens, the fact that clarifies why male subjects are more frequently affected. Thus, it is also expected that hypertensive patients treated with the ACE inhibitors could have facilitated viral invasion [4,5].…”

“…Although ACE inhibitors and angiotensin receptor blockers (ARBs) are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts during actual pandemic. Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than other ACE inhibitors or ARBs and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests [5].…”