Safety and Efficacy of Renin–Angiotensin–Aldosterone System Inhibitors in COVID-19 Population

Sattar, Yasar; Mukuntharaj, Pradeeksha; Zghouzi, Mohamed; Suleiman, Abdul-Rahman M.; Attique, Hassan; Ullah, Waqas; Sana, Muhammad Khawar; Zaher, Nathan; Mehmood, Maham; Doshi, Rajkumar P.; Panchal, Ankur; Mir, Tanveer; Nadeem, Muhammad; Ali, Omar E.; Mohamed, Mohamad; Bagur, Rodrigo; Elgendy, Islam Y.; Mamas, Mamas A.; Alraies, M. Chadi

INTRODUCTION: The safety of renin–angiotensin–aldosterone system inhibitors (RAASi) among COVID-19 patients has been controversial since the onset of the pandemic. METHODS: Digital databases were queried to study the safety of RAASi in COVID-19. The primary outcome of interest was mortality. The secondary outcome was seropositivity improvement/viral clearance, clinical manifestation progression, and progression to intensive care units. A random-effect model was used to compute an unadjusted odds ratio (OR). RESULTS: A total of 49 observational studies were included in the analysis consisting of 83,269 COVID-19 patients (RAASi n = 34,691; non-RAASi n = 48,578). The mean age of the sample was 64, and 56% were males. We found that RAASi was associated with similar mortality outcomes as compared to non-RAASi groups (OR 1.07; 95% CI 0.99–1.15; p > 0.05). RAASi was associated with seropositivity improvement including negative RT-PCR or antibodies, (OR 0.96; 95% CI 0.93–0.99; p < 0.05). There was no association between RAASi versus control with progression to ICU admission (OR 0.99; 95% CI 0.79–1.23; p > 0.05) or higher odds of worsening of clinical manifestations (OR 1.04; 95% CI 0.97–1.11; p > 0.05). Metaregression analysis did not change our outcomes for effect modifiers including age, sex, comorbidities, RAASi type, or study type on outcomes. CONCLUSIONS: COVID-19 is not a contraindication to hold or discontinue RAASi as they are not associated with higher mortality or worsening symptoms. Continuation of RAASi might be associated with favorable outcomes in COVID-19, including seropositivity/viral clearance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40292-021-00462-w.