Adrish et al. (12) |
United States |
Observational |
469 |
279 / 190 |
ACEi / ARB vs. non-ACEi / ARB |
Survival time from admission to disposition |
ACEi / ABR: ↑15 days (95% CI, 11-17) vs. 12 days (95% CI, 11-13); p=0.0062. |
Bae et al. (15) |
South Korea |
Observational |
610 |
230 / 280 |
ACEi / ARB vs. other drug |
Risk of mortality |
No differenceOR 1.00; 95% CI, 0.46 to 2.16). |
Bean et al. (32) |
United Kindgom |
Observational |
1,200 |
686 / 514 |
ACEi / ARB vs. non-ACEi / ARB |
Death or transfer to a ICU for organ support within 21-days of symptom onset |
ACEi / ABR: ↓Adjusted OR 0.63; 95% CI, 0.47 to 0.84; p<0.01. |
Bravi et al. (33) |
Italy |
Retrospective case-control |
1,603 |
758 / 844 |
ACEi / ARBs vs. non- ACEi / ARBs |
Very severe/lethal COVID-19 |
ACEi or ABR: No differenceOR 0.87; 95% CI, 0.50 to 1.49; p=0.6.ACEi: No differenceOR 0.82; 95% CI, 0.49 to 1.36; p=0.4.ARB: No differenceOR 0.83; 95% CI, 0.50 to 1.40; p=0.5. |
Cannata et al. (34) |
Italy |
Observational |
397 |
NA |
ACEi/ARB discontinuation vs. no therapyACEi/ARB continuation vs. discontinuationACEi/ARB continuation vs. no therapyACEi/ARB continuation vs. discontinuation / no therapy |
All-cause mortality |
ACEi/ARB discontinuation vs. no therapy: No differenceAdjusted OR 1.11; 95% CI, 0.36 to 3.45.ACEi/ARB continuation vs. discontinuation: No differenceAdjusted OR 0.17; 95% CI, 0.03 to 1.00.ACEi/ARB continuation vs. no therapy: ↓Adjusted OR 0.05; 95% CI, 0.01 to 0.54.ACEi/ARB continuation vs. discontinuation / no therapy: ↓Adjusted OR 0.14; 95% CI, 0.03 to 0.66. |
Conversano et al. (7) |
Italy |
Observational |
191 |
131 / 60 |
ACEi / ARB vs. non-ACEi / ARB |
All-cause mortality |
No differenceHR 0.50 (95% CI, 0.20 to 1.20; p=0.13). |
Covino et al. (8) |
Italy |
Observational |
166 |
109 / 57 |
ACEi / ARB vs. non-ACEi / ARB |
Death, and combined of death/admission to ICU |
No differenceDeath: 18% vs. 16.3%; p=0.79.Combined of death/admission to ICU: 34.2% vs. 23.6%; p=0.16. |
de Abajo et al. (35) |
Spain |
Observational |
12,529 |
7,645 / 4,884 |
ACEi / ARB vs. other antihypertensive drugs |
COVID-19 requiring admission to hospital |
ACEi: No differenceAdjusted OR 0.80; 95% CI, 0.64 to 1.00.ARB: No differenceAdjusted OR 1.10; 95% CI, 0.88 to 1.37. |
De Spiegeleer et al. (36) |
Belgium |
Observational |
154 |
51 / 103 |
ACEi / ARBs vs. non- ACEi / ARBs |
Asymptomatic status, and serious clinical outcome |
No differenceAsymptomatic status:OR 2.72; 95% CI, 0.59 to 25.1; p=0.24.Serious clinical outcome: OR 0.48; 95% CI, 0.10 to 1.97; p=0.31. |
Felice et al. (37) |
Italy |
Observational |
133 |
86 / 47 |
ACEi / ARB vs. other antihypertensive drugs |
Hospital admission, oxygen therapy, admission to ICU/sICU, non-invasive ventilation, and death |
No differenceHospital admission: adjusted OR 0.39; 95% CI, 0,05 to 2.94; p=0.36.Oxygen therapy: adjusted OR 0.51; 95% CI, 0.15 to 1.78; p=0.29.Non-invasive ventilation: adjusted OR 0.58; 95% CI, 0.21 to 1.60; p=0.29.Death: adjusted OR 0.56; 95% CI, 0.17 to 1.83; p=0.34.ACEi / ARB: ↓ Admission to ICU/sICUAdjusted OR 0.25; 95% CI, 0.09 to 0.66; p=0.006. |
Fosbøl et al. (27) |
Denmark |
Observational |
4,480 |
|
ACEi / ARB vs. non-ACEi / ARB |
Composite outcome of death or severe COVID-19 |
No differenceAdjusted HR 1.04; 95% CI, 0.89 to 1.23. |
Gao et al. (38) |
China |
Observational |
850 |
443 / 407 |
ACEi / ARB vs. other antihypertensive drugs |
Mortality rates |
No differenceAdjusted HR 0.85; 95% CI, 0.28 to 2.58; p=0.77. |
Hakeam et al. (20) |
Saudi Arabia |
Observational |
338 |
201 / 137 |
ACEi / ARB vs. non-ACEi / ARB |
ICU admission, ICU admission within 24 hours of hospitalization, ICU stay (days), and ICU death |
No differenceICU admission: 28.2% vs. 35.5%; p=0.19.ICU admission within 24 hours of hospitalization: 63.8% vs. 51.5%; p=0.23.ICU stay (days): 10.5 vs. 7; p=0.13.ICU death: 21.7% vs. 21.2%; p=0.58. |
Hippisley-Cox et al. (39) |
England |
Observational |
19,486 |
9,376 / 10,110 |
ACEi / ARBs vs. non- ACEi / ARBs |
Risk of COVID-19, risk of ICU care |
ACEi/ARBsRisk of COVID-19: ↓Adjusted HR 0.71; 95% CI, 0.67 to 0.74.Risk of ICU care: No differenceAdjusted HR 0.89; 95% CI, 0.75 to 1.06. |
Huang et al. (6) |
China |
Observational |
50 |
27 / 23 |
RAAS inhibitors vs. non-RAAS inhibitors |
In hospital mortality |
No difference0% vs. 6.67%; p=0.51 |
Jung et al. (17) |
Korea |
Observational |
5,179 |
2,295 / 2,884 |
ACEi / ARB vs. non-ACEi / ARB |
Risk of mortality |
No differenceAdjusted OR 0.88; 95% CI, 0.53 to 1.44; p=0.60). |
Khan et al. (24) |
Scotland |
Observational |
88 |
50 / 38 |
ACEi / ARB vs. non-ACEi / ARB |
Critical care admission, intubated and ventilated, and in-patient mortality |
No differenceCritical care admission: 33.3% vs. 14.7%; p=0.08.Intubated and ventilated: 18.5% vs. 11.5%; p=0.58.In-patient mortality: 18.5% vs. 22.9%; p=0.85. |
Kim et al. (18) |
Korea |
Observational |
1,378,052 |
649,153 / 728,899 |
ARB vs. non-ARB |
Risk of COVID-19 |
ARB: ↓Adjusted RR 0.75; 95% CI, 0.59 to 0.96). |
Kocayigit et al. (25) |
Turkey |
Observational |
169 |
79 / 90 |
ACEi / ARB vs. other antihypertensive drugs |
In-hospital mortality |
No differenceOR 0.53; 95% CI, 0.13 to 2.14; p=0.37. |
Lam et al. (13) |
United States |
Observational |
614 |
338 / 276 |
ACEi/ARB continuation in the hospital vs. discontinuation |
Mortality, and ICU admission |
ACEi/ARB continuation: ↓Mortality: OR 0.21; 95% CI, 0.10 to 0.45; adjusted p=0.001.ICU admission: OR 0.35; 95% CI, 0.19 to 0.64; p=0.001. |
Li et al. (2) |
China |
Observational |
362 |
173 / 189 |
ACEi / ARB vs. non-ACEi / ARB |
Severe and non-severe infections, non-survivors and survivors |
No differenceSevere and non-severe infections: 32.9% vs. 30.7%; p=0.65.Non-survivors and survivors: 27.3% vs. 33.0%; p=0.34. |
Liu et al. (3) |
China |
Observational |
157 |
73 / 84 |
ACEi / ARBs vs. CCBs |
Chest computed tomography time, and hospitalization time |
No differenceChest computed tomography time:HR 0.73; 95% CI, 0.45 to 1.2; p=0.87.Hospitalization time: HR 1.06; 95% CI, 0.44 to 1.1, p=0.83. |
Lopes et al. (28) |
Brazil |
Randomized clinical trial |
659 |
389 / 270 |
ACEi/ARB continuation in the hospital vs. discontinuation |
Primary outcome: number of days alive and out of the hospital; secondary outcome: all-cause death |
Primary outcome: No difference22.9 vs. 21.9; p=0.09.Secondary outcome: No difference2.8% vs. 2.7%; p=0.95. |
Mancia et al. (10) |
Italy |
Observational |
6,272 |
3,969 / 2,303 |
ACEi / ARBs vs. non- ACEi / ARBs |
Association with COVID-19, and severe or fatal course of the disease |
ARB: No differenceAssociation with COVID-19: adjusted OR 0.95; 95% CI, 0.86 to 1.05.Severe or fatal course of the disease: adjusted OR 0.83; 95% CI, 0.63 to 1.10.ACEi: No differenceAssociation with COVID-19: adjusted OR 0.96; 95% CI, 0.87 to 1.07.Severe or fatal course of the disease: adjusted OR 0.91; 95% CI, 0.69 to 1.21. |
Mehta et al. (40) |
United States |
Observational |
3,470 |
1,718 / 1,752 |
ACEi / ARB vs. non-ACEi / ARB |
Admitted to hospital, admitted to ICU, and use of ventilator |
ACEi:↑ Admitted to hospital: OR 1.84; 95% CI, 1.22 to 2.79.↑ Admitted to ICU: OR 1.77; 95% CI, 1.07 to 2.92.Use of ventilator: OR 1.35; 95% CI, 0.74 to 2.47.ARB:↑ Admitted to hospital: OR 1.61; 95% CI, 1.04 to 2.50.Admitted to ICU: OR 1.16; 95% CI, 0.67 to 2.02.Use of ventilator: OR 1.12; 95% CI, 0.59 to 2.12. |
Pan et al. (41) |
China |
Observational |
282 |
143 / 139 |
ACEi / ARB vs. other antihypertensive drugs |
All-cause mortality, and proportion of critically ill |
ACEi / ABR: ↓ All-cause mortality9.8% vs. 26.1%; p=0.03Proportion of critically ill: No difference31.7% vs. 43.2%; p=0.16. |
Reynolds et al. (14) |
United States |
Observational |
4,357 |
2,214 / 2,143 |
ACEi / ARB vs. non-ACEi / ARB |
Severe COVID-19 |
ACEi: No differenceMedian difference -3.3; 95% CI, -8.2 to 1.7.ARB: No differenceMedian difference 0.1; 95% CI, -4.8 to 4.9. |
Sardu et al. (11) |
Italy |
Observational |
62 |
41 / 21 |
ACEi / ARBs vs. CCBs |
Hospital admission at ICU, mechanical ventilation, cardiac injury, and death |
No difference |
Savarese et al. (21) |
Sweden |
Observational |
1,387,746 |
722,900 / 664,846 |
ACEi / ARB vs. non-ACEi / ARB |
Risk of hospitalization/death for Covid-19 in the overall population, and risk of all-cause death in patients with COVID-19 |
ACEi/ARB: ↓Risk of hospitalization/death for COVID-19 in the overall population: Adjusted OR 0.86; 95% CI, 0.82 to 0.91.Risk of all-cause death in patients with COVID-19: Adjusted HR 0.90; 95% CI, 0.83 to 0.97). |
Şenkal et al. (26) |
Turkey |
Observational |
611 |
363 / 248 |
ACEi / ARB vs. other antihypertensive drugs |
Severe disease |
ACEi: ↓OR 0.37, 95% CI, 0.15 to 0.87; p=0.03.ARB: No differenceOR 0.60, 95% CI, 0.27 to 1.36; p=0.31. |
Seo et al. (16) |
South Korea |
Observational |
4,932 |
2,142 / 2,790 |
ACEi / ARB vs. non-ACEi / ARB |
COVID-19 infection, and death |
No differenceCOVID-19 infection: Adjusted OR 0.98; 95% CI, 0.85 to 1.13.Death: Adjusted OR 0.87; 95% CI, 0.55 to 1.40. |
Son et al. (19) |
South Korea |
Observational |
2,847 |
1,449 / 1.398 |
ACEi / ARB vs. non-ACEi / ARB |
COVID-19 infection, long-term hospitalization, ICU admission, high-flow oxygen therapy, and death |
No differenceCOVID-19 infection: Adjusted OR 1.16; 95% CI, 0.96 to 1.41.Long-term hospitalization: Adjusted OR 0.86; 95% CI, 0.53 to 1.40.ICU admission: Adjusted OR 1.51; 95% CI, 0.40 to 5.70; p>0.05.High-flow oxygen therapy: Adjusted OR 0.66; 95% CI, 0.28 to 1.62; p>0.05.Death: Adjusted OR 1.36; 95% CI, 0.51 to 3.66; p>0.05. |
Tetlow et al. (23) |
London |
Observational |
557 |
320 / 237 |
ACEi / ARB vs. non-ACEi / ARB |
Macrovascular thrombus, acute kidney injury, and in-hospital mortality |
No differenceMacrovascular thrombus: Overlap propensity score - RR 1.05; 95% CI, 0.48 to 2.31.Acute kidney injury: Overlap propensity score - RR 1.04; 95% CI, 0.71 to 1.52.In-hospital mortality: Overlap propensity score - RR 1.04; 95% CI, 0.80 to 1.36. |
COVID-19 RISk and Treatments Collaboration (9) |
Italy |
Observational |
4,069 |
1,560 / 2,509 |
ACEi / ARB vs. non-ACEi / ARB |
In-hospital death |
ACEi: No differenceAdjusted HR 0.96; 95% CI, 0.77 to 1.20.ARB: No differenceAdjusted HR 0.89; 95% CI, 0.67 to 1.19. |
Vila-Corcoles et al. (22) |
Spain |
Observational |
34,936 |
16,805 / 18,131 |
ACEi / ARB vs. non-ACEi / ARB |
Risk of COVID-19 |
ACEi: No differenceHR 0.83; 95% CI, 0.61 to 1.13/ p=0.24.ARB: No differenceHR 0.67; 95% CI, 0.44 to 1.01; p=0.05. |
Wang et al. (4) |
China |
Observational |
210 |
100 / 110 |
ACEi / ARB vs. non-ACEi / ARB |
Death during hospitalization, days of hospital stay, adverse events |
No differenceDeath during hospitalization: 8.64% vs. 3.88%; p=0.15.Days of hospital stay: 17.00 vs. 17.00; p=0.82.Adverse events: 5.24% vs. 6.17%; p=0.63. |
Xu et al. (42) |
China |
Observational |
101 |
53 / 48 |
ACEi / ARB vs. other antihypertensive drugs |
In-hospital mortality, ICU admission, or invasive mechanical ventilation |
No differenceIn-hospital mortality: 28% vs. 34%; p=0.46.ICU admission: 20% vs. 28%; p=0.37.Invasive mechanical ventilation: 18% vs. 26%; p=0.31. |
Yang et al. (5) |
China |
Observational |
126 |
62 / 64 |
ACEi / ARB vs. non-ACEi / ARB |
Proportion of critical patients, and death rate |
No differenceProportion of critical patients: 9.3% vs. 22.9%; p=0.06.Death rate: 4.7% vs. 13.3%; p=0.21. |
Zhang et al. (43) |
China |
Observational |
1,128 |
603 / 525 |
ACEi / ARB vs. non-ACEi / ARB |
Risk for all-cause mortality, and COVID-19 mortality |
ACE / ARB: ↓Risk for all-cause mortality: Adjusted HR 0.42; 95% CI, 0.19 to 0.92; p=0.03.COVID-19 mortality: Adjusted HR 0.37; 95% CI, 0.15 to 0.89; p=0.03. |
Zhou et al. (44) |
China |
Observational |
3,572 |
NA |
ACEi / ARB vs. other antihypertensive drugs |
28-day all-cause death of COVID-19 |
ACEi / ARB: ↓Adjusted HR 0.39; 95% CI, 0.26 to 0.58; p<0.001. |