Ahmad A Alamer1,2, Abdulaziz S Almulhim3, Ahmed A Alrashed4, Ivo Abraham1,5. 1. Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 1295 N Martin Ave, Tucson, AZ 85721, USA. 2. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia. 3. Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahasa 31982, Saudi Arabia. 4. Pharmaceutical Service Department, Main Hospital, King Fahad Medical City, Riyadh 11564, Saudi Arabia. 5. Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Abstract
BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. METHODS: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). RESULTS: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. CONCLUSION: The country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.
BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. METHODS: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). RESULTS: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. CONCLUSION: The country-cluster meta-analysis provided a reasonable explanation for COVID-19mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.
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Authors: Seth Flaxman; Swapnil Mishra; Axel Gandy; H Juliette T Unwin; Thomas A Mellan; Helen Coupland; Charles Whittaker; Harrison Zhu; Tresnia Berah; Jeffrey W Eaton; Mélodie Monod; Azra C Ghani; Christl A Donnelly; Steven Riley; Michaela A C Vollmer; Neil M Ferguson; Lucy C Okell; Samir Bhatt Journal: Nature Date: 2020-06-08 Impact factor: 49.962