TY - JOUR
T1 - Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients
AU - Trifirò, Gianluca
AU - Massari, Marco
AU - Da Cas, Roberto
AU - Menniti Ippolito, Francesca
AU - Sultana, Janet
AU - Crisafulli, Salvatore
AU - Giorgi Rossi, Paolo
AU - Marino, Massimiliano
AU - Zorzi, Manuel
AU - Bovo, Emanuela
AU - Leoni, Olivia
AU - Ludergnani, Monica
AU - Spila Alegiani, Stefania
AU - Spila Alegiani, Stefania
AU - ITA-COVID-19: RAAS inhibitor group
N1 - Funding Information:
Marco Massari, Roberto Da Cas, Francesca Menniti Ippolito, Janet Sultana, Salvatore Crisafulli, Paolo Giorgi Rossi, Massimiliamo Marino, Manuel Zorzi, Emanuela Bovo, Olivia Leoni, Monica Ludergnani and Stefania Spila Alegiani have no conflicts of interest to disclose. Gianluca Trifirò reports grants from Novartis, from the Italian Drug Agency, during the conduct of the study; has participated in advisory boards within the last 5 years on topics not related to this article and organised by Sandoz, Hospira, Sanofi, Biogen, Ipsen, and Shire; and is a consultant for Otsuka. He is the principal investigator of observational studies funded by several pharmaceutical companies (e.g. Amgen, AstraZeneca, Daiichi Sankyo, IBSA) to the University of Messina, as well as thescientific coordinator of the Master’s programme ‘Pharmacovigilance, Pharmacoepidemiology and Pharmacoeconomics: Real-World Data Evaluations’ at the University of Messina, which receives unconditional funding from several pharmaceutical companies.
Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Introduction: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. Objective: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. Methods: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. Results: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89–1.06) or ARB (HR 0.98, 95% CI 0.89–1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. Conclusions: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.
AB - Introduction: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. Objective: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. Methods: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. Results: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89–1.06) or ARB (HR 0.98, 95% CI 0.89–1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. Conclusions: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.
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U2 - 10.1007/s40264-020-00994-5
DO - 10.1007/s40264-020-00994-5
M3 - Article
C2 - 32852721
AN - SCOPUS:85089985922
VL - 43
SP - 1297
EP - 1308
JO - Drug Safety
JF - Drug Safety
SN - 0114-5916
IS - 12
ER -