Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Data Collection
2.3. Main Outcomes
2.4. Statistical Analysis
2.5. Ethics
3. Results
3.1. Study Population
3.2. Outcomes of Prognosis
3.3. Major Adverse Cardiovascular Events
3.4. ACEI/ARB Continuation Versus Withdrawal during Hospitalization
3.5. Comparison between ACEI and ARB
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total Population (n = 11,205) | Non-ACEI/ARB Group (n = 9043) | ACEI/ARB Group (n = 2162) | p-Value | |
---|---|---|---|---|
Age (years): mean (SD) | 67.0 (16.3) | 65.7 (16.8) | 72.5 (12.5) | <0.0001 |
Female sex (%) | 4827/11,190 (43.1%) | 3944/9030 (43.7%) | 883/2160 (40.9%) | 0.018 |
Race/Ethnicity (%) | ||||
Caucasian | 9831/11,014 (89.3%) | 7836/8886 (88.2%) | 1995/2128 (93.8%) | <0.001 * |
African | 45/11,014 (0.4%) | 36/8886 (0.4%) | 9/2128 (0.4%) | |
Latin American | 990/11,014 (9.0%) | 892/8886 (10.0%) | 98/2128 (4.6%) | |
Asian | 50/11,014 (0.5%) | 43/8886 (0.5) | 7/2128 (0.3%) | |
Other | 98/11,014 (0.9%) | 79/8886 (0.9%) | 19/2128 (0.9%) | |
Smoking (%) | ||||
Non-smoker | 7438/10,699 (69.5%) | 6125/8617 (71.1%) | 1313/2082 (63.1%) | <0.001 * |
Former smoker | 2686/10,699 (25.0%) | 2030/8617 (23.6%) | 656/2082 (31.5%) | |
Active smoker | 575%10,699 (5.4%) | 462/8617 (5.4%) | 113/2082 (15.4%) | |
Alcohol use disorder (%) | 516/10,887 (4.7%) | 387/8780 (4.4%) | 129/2107 (6.1%) | 0.001 |
Comorbidities (%) | ||||
Hypertension | 5576/11,190 (49.8%) | 3589/9033 (39.7%) | 1987/2157 (92.1%) | <0.001 |
Dyslipidemia | 4415/11,189 (39.5%) | 3231/9029 (35.8%) | 1184/2160 (54.8%) | <0.001 |
Diabetes mellitus | 2095/11,178 (18.7%) | 1464/9022 (16.2%) | 631/2156 (29.3%) | <0.001 |
Obesity | 2186/10,212 (21.4%) | 1618/8242 (19.6%) | 568/1970 (28.8%) | <0.001 |
Heart failure | 811/11,186 (7.3%) | 594/9030 (6.6%) | 217/2156 (10.1%) | <0.001 |
Ischemic heart disease | 880/11,193 (7.9%) | 591/9032 (6.5%) | 289/2161 (13.4%) | <0.001 |
Cerebrovascular disease | 797/11,173 (7.1%) | 598/9018 (6.6%) | 199/2155 (9.2%) | <0.001 |
Peripheral artery disease | 523/11,183 (4.7%) | 387/9026 (4.3%) | 136/2157 (6.3%) | <0.001 |
Chronic kidney disease | 665/11,183 (5.9%) | 491/9026 (5.4%) | 174/2157 (8.1%) | <0.001 |
Age-adjusted Charlson Comorbidity Index: points (SD) | 3.6 (2.7) | 3.4 (2.7) | 4.4 (2.47) | <0.0001 |
Previous treatment (%) | ||||
ACEI | 1890/11,205 (16,9%) | 993/9043 (11.0%) | 897/2162 (41.5%) | <0.001 |
ARB | 2133/11,205 (19.0%) | 1103/9043 (12.2%) | 1030/2162 (47.6%) | <0.001 |
Outcome | Non-ACEI/ARB Group | ACEI/ARB Group | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
RR (95%CI) | p-Value | RR (95%CI) | p-Value | |||
Composite variable of prognosis: IMV, NIMV, ICU admission, or death * | 2443/8854 (27.6%) | 569/2107 (27.0%) | 0.98 (0.91–1.06) | 0.6064 | Normotensive: 1.12 (0.90–1.38) Hypertensive: 0.68 (0.62–0.75) | 0.3085 <0.0001 |
IMV * | 622/9024 (6.9%) | 115/2157 (5.3%) | 0.77 (0.64–0.94) | 0.0100 | Normotensive: 2.07 (1.42–3.02) Hypertensive: 0.50 (0.39–0.64) | 0.0002 <0.0001 |
NIMV | 396/9026 (4.4%) | 130/2156 (6.0%) | 1.37 (1.13–1.67) | 0.0015 | 1.13 (0.90–1.43) | 0.2908 |
ICU admission * | 767/9035 (8.5%) | 148/2161 (6.8%) | 0.81 (0.68–0.96) | 0.0140 | Normotensive: 1.76 (1.23–2.52) Hypertensive: 0.57 (0.46–0.71) | 0.0019 <0.0001 |
Death | 1897/8853 (21.4%) | 436/2105 (20.7%) | 0.97 (0.88–1.06) | 0.4897 | 0.65 (0.59–0.72) | <0.0001 |
Comparison | Adjusted HR | 95%CI | p-Value |
---|---|---|---|
ACEI/ARB vs. non-ACEI/ARB during hospitalization | From the onset of symptoms: At 7 days: 0.57 At 30 days: 0.68 | 0.49–0.66 0.55–0.85 | <0.001 0.001 |
ACEI/ARB continued vs. withdrawn | From the onset of symptoms: At 7 days: 0.52 At 30 days: 0.79 | 0.44–0.60 0.60–1.05 | <0.001 0.110 |
ARB vs. ACEI | 0.77 | 0.62–0.96 | 0.027 |
Outcome | Non-ACEI/ARB Group | ACEI/ARB Group | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
RR (95%CI) | p-Value | RR (95%CI) | p-Value | |||
Major adverse cardiovascular events (MACE): MI, HF, stroke, arrhythmia | 827/8986 (9.2%) | 257/2144 (12.0%) | 1.30 (1.14–1.49) | 0.0001 | 0.94 (0.81–1.09) | 0.4211 |
MI | 60/9005 (0.7%) | 28/2151 (1.3%) | 1.95 (1.23–3.05) | 0.0043 | 1.64 (0.93–2.89) | 0.0877 |
HF | 504/9010 (5.6%) | 160/2150 (7.4%) | 1.33 (1.12–1.58) | 0.0014 | 1.03 (0.85–1.26) | 0.7597 |
Stroke | 51/9003 (0.6%) | 18/2153 (0.8%) | 1.48 (0.86–2.52) | 0.2005 | 0.90 (0.46–1.73) | 0.7435 |
Arrhythmia | 347/9002 (3.9%) | 104/2152 (4.8%) | 1.25 (1.01–1.55) | 0.0446 | 0.86 (0.66–1.11) | 0.2335 |
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Roy-Vallejo, E.; Sánchez Purificación, A.; Torres Peña, J.D.; Sánchez Moreno, B.; Arnalich, F.; García Blanco, M.J.; López Miranda, J.; Romero-Cabrera, J.L.; Herrero Gil, C.R.; Bascunana, J.; et al. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19. J. Clin. Med. 2021, 10, 2642. https://doi.org/10.3390/jcm10122642
Roy-Vallejo E, Sánchez Purificación A, Torres Peña JD, Sánchez Moreno B, Arnalich F, García Blanco MJ, López Miranda J, Romero-Cabrera JL, Herrero Gil CR, Bascunana J, et al. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19. Journal of Clinical Medicine. 2021; 10(12):2642. https://doi.org/10.3390/jcm10122642
Chicago/Turabian StyleRoy-Vallejo, Emilia, Aquilino Sánchez Purificación, José David Torres Peña, Beatriz Sánchez Moreno, Francisco Arnalich, María José García Blanco, José López Miranda, Juan Luis Romero-Cabrera, Carmen Rosario Herrero Gil, José Bascunana, and et al. 2021. "Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19" Journal of Clinical Medicine 10, no. 12: 2642. https://doi.org/10.3390/jcm10122642