Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Design and Patient Selection
2.2. Baseline Variables
2.3. Outcome Assessment
2.4. Statistical Analysis
3. Results
3.1. Patients Characteristics at Baseline
3.2. In-Hospital Outcomes
3.3. Survivors Versus Nonsurvivors
3.4. Mild Versus Severe Forms of COVID-19 Infection
3.5. ACEIs Versus ARBs and Poor Outcomes
4. Discussion
4.1. Main Results in Brief
4.2. Hypothetical Pathogenic Mechanisms of RASi Impact on COVID-19 Evolution
4.3. Poor Prognosis Risk Factors
4.4. ACEIs Versus ARBs
4.5. Evidence in the Available Literature
4.6. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Overall Cohort | PS Cohort | |||||
---|---|---|---|---|---|---|
RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | |
N | 282 | 490 | 113 | 113 | ||
Age (years) | 75 (66–83) | 64 (50–75) | <0.001 | 73 (64–84) | 73 (61–85) | 0.61 |
Age ≥ 65 years old | 221 (78.4) | 243 (49.6) | <0.001 | 84 (74.3) | 80 (70.8) | 0.65 |
Male | 170 (60.3) | 274 (55.9) | 0.27 | 68 (60.2) | 61 (54) | 0.42 |
BMI (kg/m2) (N = 662) | 28 (25–33) | 27 (24–31) | 0.004 | 27 (24–31) | 26 (24–31) | 0.69 |
eGFR (mL/min/1.73 m2) on admission (N = 756) | 68 (44–84) | 88 (68.5–102.5) | <0.001 | 70 (44–84) | 77 (43–93) | 0.26 |
eGFR ≥ 90 | 45 (16) | 231 (48.6) | 22 (19.6) | 35 (30.9) | 0.07 | |
60 ≤ eGFR < 90 | 122 (43.4) | 143 (30.1) | 44 (39.3) | 32 (28.3) | 0.11 | |
30 ≤ eGFR < 60 | 76 (27) | 66 (13.9) | 32 (28.6) | 27 (23.9) | 0.51 | |
eGFR < 30 | 38 (13.5) | 35 (7.4) | 14 (12.5) | 19 (16.8) | 0.47 | |
Cardiovascular risk factors | ||||||
Hypertension (N = 769) | 273 (96.8) | 158 (32.4) | <0.001 | 104 (92) | 104 (92) | 1 |
Diabetes (N = 769) | 134 (47.5) | 85 (17.5) | <0.001 | 40 (35.4) | 34 (30.1) | 0.48 |
Dyslipidemia (N = 769) | 166 (58.9) | 107 (21.9) | <0.001 | 60 (53.1) | 56 (49.6) | 0.69 |
Smoking (history or current) (N = 671) | 70 (27.9) | 85 (20.2) | 0.029 | 35 (31) | 34 (30.1) | 1 |
Obesity (N = 690) | 107 (42.1) | 134 (30.7) | 0.003 | 35 (31) | 35 (31) | 1 |
Medical history | ||||||
Heart disease (N = 768) | 83 (29.4) | 41 (8.4) | <0.001 | 22 (19.5) | 23 (20.3) | 1 |
Ischemic heart disease | 65 (23) | 26 (5.3) | <0.001 | 14 (12.4) | 12 (10.6) | 0.83 |
Chronic heart failure | 24 (8.5) | 19 (3.9) | 0.011 | 7 (6.2) | 10 (8.8) | 0.61 |
HFrEF | 16 (5.7) | 8 (1.6) | 0.004 | 4 (3.5) | 4 (3.5) | 1 |
Chronic kidney disease (N = 769) | 61 (21.6) | 51 (10.5) | <0.001 | 26 (23) | 31 (27.4) | 0.54 |
Chronic respiratory disease (N = 769) | 35 (12.4) | 56 (11.5) | 0.80 | 12 (10.6) | 16 (14.2) | 0.53 |
COPD | 22 (7.8) | 23 (4.7) | 0.11 | 8 (7.1) | 10 (8.9) | 0.79 |
Active cancer | 19 (6.7) | 34 (6.9) | 1 | 5 (4.4) | 11 (9.7) | 0.20 |
Cognitive impairment (N = 768) | 48 (17.1) | 47 (9.7) | 0.003 | 18 (15.9) | 20 (17.7) | 0.85 |
VTE (N = 769) | 27 (9.6) | 31 (6.4) | 0.138 | 13 (11.5) | 14 (12.4) | 1 |
Admission treatment | ||||||
Antithrombotic treatment on admission | 159 (56.8) | 108 (22.2) | <0.001 | 55 (48.7) | 53 (46.9) | 0.89 |
Antiplatelet (N = 766) | 107 (38.4) | 61 (12.5) | <0.001 | 40 (35.4) | 28 (24.8) | 0.11 |
Anticoagulation (N = 765) | 61 (21.9) | 57 (11.7) | <0.001 | 16 (14.2) | 28 (24.8) | 0.07 |
Antihypertensive drugs (N = 767) | ||||||
Diuretics | 116 (41.4) | 60 (12.3) | <0.001 | 42 (37.2) | 41 (36.3) | 1 |
Beta-blockers | 121 (43.4) | 94 (19.3) | <0.001 | 46 (40.7) | 52 (46) | 0.50 |
COVID-19 diagnosis | ||||||
Positive PCR | 282 (100) | 490 (100) | - | 113 (100) | 113 (100) | |
Low-dose chest CT | 230 (81.6) | 388 (79.2) | 0.42 * | 91 (97.8) | 81 (94.2) | 0.38 * |
normal | 3 (1.3) | 14 (3.6) | 2 (2.2) | 5 (5.8) | ||
uncertain abnormalities | 5 (2.2) | 7 (1.8) | 2 (2.2) | 3 (3.5) | ||
minimal abnormalities (<10%) | 33 (14.3) | 51 (13.1) | 14 (15) | 9 (10.5) | ||
moderate abnormalities (10–25%) | 78 (33.9) | 128 (33) | 27 (29) | 33 (38.4) | ||
important abnormalities (25–50%) | 54 (23.5) | 108 (27.8) | 29 (31.2) | 19 (22.1) | ||
severe abnormalities (50–75%) | 43 (18.7) | 65 (16.8) | 16 (17.2) | 14 (16.3) | ||
critical abnormalities (>75%) | 14 (6.1) | 15 (3.9) | 3 (3.2) | 3 (3.5) | ||
COVID-19 infection severity indicators | ||||||
Oxygen therapy flow rate of >5 L/min | 172 (61) | 247 (50.4) | 0.015 | 67 (59.8) | 55 (51.4) | 0.26 |
Intubation/HNFO therapy/NIV | 82 (29.1) | 151 (30.8) | 0.67 | 38 (33.6) | 30 (26.5) | 0.31 |
Intubation | 80 (28.4) | 140 (28.6) | 1 | 38 (33.6) | 26 (23) | 0.10 |
HFNO therapy/NIV | 11(3.9) | 2 (0.4) | 0.14 | 0 | 4 (3.5) | 0.12 |
CT scan extension > 25% (N = 618) | 111 (48.3) | 188 (48.5) | 1 | 0 | 4 (3.5) | 0.12 |
CRP ≥ 100 mg/L (N = 746) | 182 (65.7) | 293 (62.5) | 0.42 | 71 (64.5) | 68 (60.2) | 0.59 |
D-dimer count ≥ 1500 µg/L (N = 350) | 99 (76.1) | 151 (68.6) | 0.16 | 48 (82.8) | 35 (70) | 0.18 |
Lymphopenia < 1000/µL (N = 753) | 208 (174) | 347 (73.5) | 0.95 | 85 (75.9) | 86 (77.5) | 0.90 |
hs-cTnl ≥ 100 ng/L (N = 376) | 37 (24.8) | 40 (17.6) | 0.12 | 14 (20.9) | 12 (21.4) | 1 |
Total N(%)/M(IQR) | RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | |
---|---|---|---|---|
N | 772 | 282 | 490 | |
Death | 173 (21.5) | 82 (29.1) | 91 (18.6) | <0.001 |
Death/intubation | 322 (41.7) | 133 (47.2) | 189 (38.6) | 0.019 |
Death/intubation/HFNO therapy/NIV | 332 (43) | 133 (47.2) | 199 (40.6) | 0.077 |
Death/intubation/HFNO therapy/NIV/oxygen flow rate of ≥5 L | 438 (56.7) | 179 (63.5) | 259 (52.9) | 0.004 |
Death/intubation/HFNO therapy/NIV/oxygen flow rate of ≥10 L | 358 (46.4) | 144 (51) | 214 (43.7) | 0.047 |
Acute renal impairment (N = 767) | 212 (27.6) | 105 (37.5) | 107 (22) | <0.001 |
Severe sepsis or septic shock (N = 698) | 132 (18.9) | 55 (22.2) | 77 (17.1) | 0.103 |
Pulmonary bacterial infection (N = 747) | 60 (8) | 25 (9.2) | 35 (7.4) | 0.36 |
Multiple organ deficiency (N = 767) | 36 (4.5) | 16 (5.7) | 20 (4.1) | 0.31 |
VTE | 61 (7.9) | 21 (7.4) | 40 (8.2) | 0.72 |
AF (N = 748) | 37 (4.9) | 14 (5.2) | 23 (4.8) | 0.83 |
Stroke | 20 (2.6) | 10 (3.5) | 10 (0.2) | 0.21 |
Major bleeding | 37 (4.8) | 14 (5) | 23 (4.7) | 0.87 |
Encephalitis | 15 (1.9) | 6 (2.1) | 9 (1.8) | 0.86 |
Liver injury (N = 748) | 18 (1.6) | 5 (1.8) | 13 (2.7) | 0.60 |
Hospital length of stay | 11 (6–21) | 12 (7–24) | 10 (6–20) | 0.45 |
Hospital length of stay of ≥30 days | 128 (16.6) | 51 (18.1) | 77 (15.7) | 0.21 |
Total N (%)/m ± sd/ M(Q1–Q3) | Nonsurvivors N (%)/m ± sd/ M(Q1–Q3) | Survivors N (%)/m ± sd/ M(Q1–Q3) | p-Value | |
---|---|---|---|---|
N | 772 | 173 | 599 | |
Age (years) | 68 (56–79) | 79 (71–85) | 65 (53–76) | <0.001 |
Age ≥ 65 years old | 464 (60.1) | 156 (90.2) | 308 (51.4) | <0.001 |
Male | 444 (57.5) | 108 (62.4) | 336 (56.1) | 0.16 |
BMI (kg/m2) N = 662 | 28 (24–31) | 27 (24–31) | 28 (24–31) | 0.10 |
Cardiovascular risk factors | ||||
Hypertension N = 769 | 431 (56) | 129 (74.6) | 302 (50.4) | <0.001 |
Diabetes N = 769 | 219 (28.5) | 62 (35.8) | 157 (26.2) | 0.012 |
Dyslipidemia N = 769 | 273 (35.5) | 80 (46.5) | 193 (32.3) | <0.001 |
Smoking (history or current) N = 671 | 155 (23.1) | 49 (31.4) | 106 (20.4) | 0.0042 |
Obesity N = 690 | 241 (34.9) | 50 (31.6) | 191 (35.9) | 0.32 |
Medical history | ||||
Heart disease N = 768 | 124 (16.1) | 37 (21.5) | 87 (14.6) | 0.029 |
Ischemic heart disease | 91 (11.8) | 58 (19.1) | 33 (9.7) | <0.001 |
Chronic heart failure N = 769 | 43 (5.6) | 21 (12.2) | 22 (3.7) | <0.001 |
HFrEF | 24 (3.1) | 12 (6.9) | 12 (2) | <0.001 |
Chronic kidney disease N = 769 | 112 (14.6) | 55 (31.9) | 57 (9.5) | <0.001 |
Chronic respiratory disease N = 769 | 91 (11.8) | 26 (15.1) | 65 (10.8) | 0.13 |
COPD | 45 (5.9) | 14 (8.1) | 31 (5.2) | 0.14 |
Active cancer | 53 (6.9) | 26 (15) | 27 (4.5) | <0.001 |
Cognitive impairment N = 768 | 95 (12.4) | 46 (36.4) | 49 (8.2) | <0.001 |
VTE N = 769 | 58 (7.5) | 19 (11) | 39 (6.5) | 0.048 |
Admission treatment | ||||
Antithrombotic treatment | 267 (34.8) | 99 (57.9) | 168 (28.2) | <0.001 |
Antiplatelet N = 767 | 168 (21.9) | 57 (33.3) | 111 (18.6) | <0.001 |
Anticoagulation N = 766 | 118 (15.4) | 52 (30.5) | 66 (11.1) | <0.001 |
Antihypertensive drugs | ||||
ACE or ARBs | 282 (36.5) | 82 (47.4) | 200 (33.4) | 0.001 |
Diuretics | 176 (22.9) | 69 (40.6) | 107 (17.9) | <0.001 |
Beta-blockers | 215 (28.1) | 70 (41.2) | 145 (24.3) | <0.001 |
COVID-19 diagnosis | ||||
Positive PCR | 772 (100) | 173 (100) | 599 (100) | |
Low-dose CT | 618 (80) | 118 (68.2) | 500 (83.5) | <0.001 * |
normal | 17 (2.8) | 2 (1.1) | 15 (2.5) | 0.67 § |
uncertain abnormalities | 12 (1.9) | 6 (3.5) | 6 (1) | |
minimal (<10%) | 84 (13.6) | 9 (5.2) | 75 (12.5) | |
moderate (10–25%) | 206 (33.3) | 22 (12.7) | 184 (30.7) | |
important (25–50%) | 162 (26.2) | 36 (20.8) | 126 (21) | |
severe (50–75%) | 108 (17.5) | 33 (19.1) | 75 (12.5) | |
critical (>75%) | 29 (4.7) | 10 (5.8) | 19 (3.2) | |
COVID-19 infection severity indicators | ||||
Oxygen flow rate of ≥5 L/min | 378 (48.9) | 135 (78) | 243 (40.6) | <0.001 |
HFNO therapy/NIV/OTI | 233 (30.2) | 74 (42.8) | 159 (26.5) | <0.001 |
OTI | 220 (28.5) | 71 (41) | 149 (24.9) | <0.001 |
HFNO therapy/NIV | 13 (1.7) | 3 (1.7) | 10 (1.7) | 1 |
CRP ≥ 100 mg/L (N = 746) | 476 (63.7) | 133 (80.6) | 343 (59) | <0.001 |
Ddimer count ≥ 1500 µg/L (N = 350) | 250 (71.4) | 72 (91.1) | 178 (65.7) | <0.001 |
Lymphopenia < 1000/µL (N = 753) | 555 (73.7) | 147 (86.5) | 408 (70) | <0.001 |
hs-cTnl ≥ 100 ng/L (N = 376) | 77 (20.5) | 37 (40.6) | 40 (14) | <0.001 |
In-hospital treatment | ||||
Anticoagulant N = 769 | 625 (81.3) | 141 (82.4) | 484 (80.9) | 0.73 |
preventive | 479 (62.2) | 84 (49.1) | 395 (66) | |
therapeutic | 145 (19) | 56 (32.7) | 89 (14.9) | |
ACEIs/ARBs | 125 (16.2) | 28 (16.2) | 97 (16.2) | 1 |
Antiviral | 286 (37) | 55 (31.8) | 231 (38.6) | 0.65 |
lopinavir/ritonavir | 153 (19.8) | 29 (16.7) | 124 (20.7) | |
remdesivir | 7 (0.9) | 0 | 7 (1.2) | |
oseltamivir | 2 (0.5) | 1 (0.6) | 1 (0.2) | |
hydoxychroloquine | 140(18.1) | 30 (17.3) | 110 (18.4) | |
IFN | 4 (0.5) | 0 | 4 (0.7) | |
Antibiotics | 634 (82.1) | 141 (81.5) | 493(82.3) | 0.32 |
amoxicillin/clavulanic acid | 239 (31) | 31 (17.9) | 208 (34.7) | |
3GC | 414 (53.6) | 109 (63) | 305 (50.9) | |
macrolide | 321 (41.6) | 74 (42.8) | 247 (41.2) | |
quinolone | 13 (1.7) | 5 (2.9) | 8 (1.3) | |
other | 3 (0.4) | 2 (1.2) | 1 (0.2) |
Outcome | ACEIs N (%) n = 129 | ARBs N (%) n = 152 | Unadjusted OR ACEIs vs. ARBs (95%CI) | p-Value |
---|---|---|---|---|
Death | 44 (34.1) | 37 (24.3) | 1.60 (0.95–2.71) | 0.072 |
Severe pneumonia | 86 (66.6) | 92 (60.5) | 1.30 (0.80–2.13) | 0.288 |
Acute renal insufficiency | 42 (32.6) | 64 (42.1) | 0.66 (0.40–1.08) | 0.100 |
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Cordeanu, E.-M.; Jambert, L.; Severac, F.; Lambach, H.; Tousch, J.; Heitz, M.; Mirea, C.; Hamadé, A.; Younes, W.; Frantz, A.-S.; et al. Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors. J. Clin. Med. 2020, 9, 3472. https://doi.org/10.3390/jcm9113472
Cordeanu E-M, Jambert L, Severac F, Lambach H, Tousch J, Heitz M, Mirea C, Hamadé A, Younes W, Frantz A-S, et al. Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors. Journal of Clinical Medicine. 2020; 9(11):3472. https://doi.org/10.3390/jcm9113472
Chicago/Turabian StyleCordeanu, Elena-Mihaela, Lucas Jambert, Francois Severac, Hélène Lambach, Jonathan Tousch, Marie Heitz, Corina Mirea, Amer Hamadé, Waël Younes, Anne-Sophie Frantz, and et al. 2020. "Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors" Journal of Clinical Medicine 9, no. 11: 3472. https://doi.org/10.3390/jcm9113472