Usefulness of Combined Renin-Angiotensin System Inhibitors and Diuretic Treatment In Patients Hospitalized with COVID-19.

Antecedent use of renin-angiotensin system inhibitors (RASi) prevents clinical deterioration and protects against cardiovascular/thrombotic complications of COVID-19, for indicated patients. Uncertainty exists regarding treatment continuation throughout infection and doing so with concomitant medications. Hence, the purpose of this study is to evaluate the differential effect of RASi continuation in patients hospitalized with COVID-19 according to diuretic use. We used the Coracle registry, which contains data of hospitalized patients with COVID-19 from 4 regions of Italy. We used Firth logistic regression for adult (>50 years) cases with admission on/after February 22, 2020, with a known discharge status as of April 1, 2020. There were 286 patients in this analysis; 100 patients (35.0%) continued RASi and 186 (65%) discontinued. There were 98 patients treated with a diuretic; 51 (52%) of those continued RASi. The in-hospital mortality rates in patients treated with a diuretic and continued versus discontinued RASi were 8% versus 26% (p = 0.0179). There were 188 patients not treated with a diuretic; 49 (26%) of those continued RASi. The in-hospital mortality rates in patients not treated with a diuretic and continued versus discontinued RASi were 16% versus 9% (p = 0.1827). After accounting for age, cardiovascular disease, and laboratory values, continuing RASi decreased the risk of mortality by approximately 77% (odds ratio 0.23, 95% confidence interval 0.06 to 0.95, p = 0.0419) for patients treated with diuretics, but did not alter the risk in patients treated with RASi alone. Continuing RASi in patients concomitantly treated with diuretics was associated with reduced in-hospital mortality.

Renin-Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID-19.

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.

Renin-angiotensin-aldosterone system inhibitors and SARS-CoV-2 infection: an analysis from the veteran's affairs healthcare system.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are known to impact the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association between chronic therapy with these medications and infection risk remains unclear. OBJECTIVES: The objective was to determine the association between prior ACEI or ARB therapy and SARS-CoV-2 infection among patients with hypertension in the U.S. Veteran's Affairs health system. METHODS: We compared the odds of SARS-CoV-2 infection among three groups: patients treated with ACEI, treated with ARB, or treated with alternate first-line anti-hypertensives without ACEI/ARB. We excluded patients with alternate indications for ACEI or ARB therapy. We performed an augmented inverse propensity weighted analysis with adjustment for demographics, region, comorbidities, vitals, and laboratory values. RESULTS: Among 1,724,723 patients with treated hypertension, 659,180 were treated with ACEI, 310,651 with ARB, and 754,892 with neither. Before weighting, patients treated with ACEI or ARB were more likely to be diabetic and use more anti-hypertensives. There were 13,278 SARS-CoV-2 infections (0.8%) between February 12, 2020 and August 19, 2020. Patients treated with ACEI had lower odds of SARS-CoV-2 infection (odds ratio [OR] 0.93; 95% CI: 0.89-0.97) while those treated with ARB had similar odds (OR 1.02; 95% CI: 0.96-1.07) compared with patients treated with alternate first-line anti-hypertensives without ACEI/ARB. In falsification analyses, patients on ACEI did not have a difference in their odds of unrelated outcomes. CONCLUSIONS: Our results suggest the safety of continuing ACEI and ARB therapy. The association between ACEI therapy and lower odds of SARS-CoV-2 infection requires further investigation.

Hypertension, medications, and risk of severe COVID-19: A Massachusetts community-based observational study.

It remains uncertain whether the hypertension (HT) medications angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS-CoV-2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID-19) as defined by hospitalization or mortality among individuals diagnosed with COVID-19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use. In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID-19 diagnosis. In our study, pre-infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID-19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID-19 compared to 9% with less severe COVID-19 used ACEi, 8% and 4%, respectively, used ARB. In propensity score-matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID-19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID-19 severity. In conclusion, cardiovascular-related comorbidities were associated with severe COVID-19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID-19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin-angiotensin system (RAS) inhibitors to prevent severe COVID-19.