Renin–angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study

Abstract

Aim The role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin-angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome. Methods We performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors. Results Of the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37-0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26-0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18-1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28-0.92 and HR 0.82, 95% CI 0.51-1.32, respectively). Conclusions Our study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment

“…As in the case of other drugs, the potential beneficial effects of ARBs and ACEIs can be different in different patients depending on other external factors, including combinations with other treatments, patient comorbidities, and even the sex or age of the patient. In fact, beneficial effects were more clearly observed in studies that considered possible confounding factors and relevant bias in their analysis [ 31 , 136 ]. Obviously, the classical limitations of these drugs, such as the risk of potential birth defects in women that may get pregnant, must also be considered.…”

The role of the brain renin-angiotensin system in Parkinson´s disease

“…Similarly, the possible beneficial or detrimental effects of therapies with ARBs and ACE inhibitors were highly controversial [ 45 , 46 ]. Research [ 47 , 48 ] and clinical studies [ 49 , 50 ] showed the non-detrimental and possible beneficial effects of these drugs. This has been detailed in our recent review article [ 51 ].…”

Characteristics, comorbidities and laboratory measures associated with disease severity and poor prognosis in young and elderly patients with COVID-19 admitted to medical wards in Emilia-Romagna region, Italy: a multicentre retrospective study

“…[39][40][41][42][43] Fewer studies have been carried out in a single region or Hospital Center, [44][45] or have examined only some peculiar aspects concerning the impact of viral infection in human pathology. [46][47][48][49] On the other hand, while welldesigned multicenter studies allow for an improvement in the quality of the results obtained, the data collected may be heterogeneous and do not exactly reflect the characteristics, the clinical course and the prognosis of patients with COVID-19 belonging to narrower geographical areas. To date, few trials have investigated the trend of all these factors in patients with COVID-19, who have been admitted to the Internal Medicine/Cardiology Wards (IM/CW) in single Italian regions.…”