Table 1.
Main characteristics of included studies.
| Study Year | Design | Region | Population | Total/ ACEi/ARB | Control | Mean-median age / % female | Comorbidities | Outcome adjustments |
|---|---|---|---|---|---|---|---|---|
| RANDOMIZED CONTROLLED TRIAL | ||||||||
| Amat-Santos 2020 | Non-planned interim analysis of an open-label RCT | Spain | Patients with aortic stenosis successfully treated with transcatheter aortic valve replacement |
ACEi (ramipril): 52 | Placebo: 50 | 83 47% |
HTN: 54% CAD: 26% DM: 20% CKD: 33% |
– |
| CASE-CONTROL STUDIES | ||||||||
| de Abajo 2020 | Case-control study | Madrid, Spain | Case: ≥ 18 years with PCR-confirmed COVID-19 requiring hospital admission (n = 1139) Control: from database Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database (n = 11390) Matching 1:10 by sex and age |
COVID-19 positive Total: 497 ACEi: 240 ARB: 244 Aldosterone antagonists: 38 Renin inhibitors: 1 |
COVID-19 negative Total: 3822 ACEi: 2192 ARB: 1616 Aldosterone antagonists:218 Renin inhibitors: 8 |
69 61% |
HTN: 54% COVID-19+ 50% COVID-19 - CAD: 11% COVID-19+ 8% COVID-19 - DM: 27% COVID-19+ 20% COVID-19 - CKD: 8% COVID-19+ 5% COVID-19 - HF: 7% COVID-19+ 4% COVID-19 - |
Age, sex, diabetes, dyslipidemia, ischemic heart disease, heart failure, atrial fibrillation, thromboembolic disease, cerebrovascular accident, chronic obstructive pulmonary disease, asthma, cancer, and chronic kidney disease |
| Gnavi 2020 | Nested case-control study in 2 cohorts | Piedmont, Italy | Case: Discharged patients with confirmed COVID-19 infection (RT-PCR) in - Hypertensive patients (N = 316) - Cardiovasular disease* patients (N = 171) Control: Discharged patients without COVID-19 infection Matching 1:5 by sex and age |
COVID-19 positive Total: 215 ACEi: NR ARB: NR Total: 93 ACEi: NR ARB: NR |
COVID-19 negative Total: 1153 ACEi: NR ARB: NR Total: 475 ACEi: NR ARB: NR |
71 (hypertension cohort); 75 (cardiovascular disease cohort) 31% (hypertension cohort); 22% (cardiovascular disease cohort) |
HTN: 100% | Age, sex, and disease type (hypertension or cardiovascular disease) |
| Mancia 2020 | Population-based case–control study | Lombardy Italy | Case: Positive COVID-19 patients (≥40 years old) N = 6272 Control: beneficiaries of the Regional Health Service N = 30759 Matched 1:5 by sex, age at index date, and municipality of residence |
COVID-19 positive Total: 2896 ACEi: 1502 ARB: 1394 |
COVID-19 negative Total: 27863 ACEi: 6569 ARB: 5910 |
68 37% |
NR | Cardiovascular disease, respiratory disease, kidney disease, cancer, antihypertensive agents, lipid lowering agents, oral hypoglycemic agents, insulin, antiplatelet agents, antiarrhythmic agents, anticoagulant agents, digitalis, nitrates, inhaled glucocorticoids, nonsteroidal antiinflamatory drugs, immunosuppressive agents, beta agonists, other drugs for respiratory disease |
| COHORT/NESTED CASE-CONTROL STUDIES | ||||||||
| Argenziano 2020 | Single-center retrospective cohort study | New York, USA | Patients with hypertension and diabetes admitted in the emergency department or in the hospital for COVID-19 infection N = 1000 |
Total: 284 ACEI: NR ARB: NR |
Non-ACEi/ARB: 716 |
63 40% |
HTN: 60% CAD: 13% DM: 37% CKD: 14% HF: 10% |
– |
| Bean 2020 | Retrospective cohort study | London, UK |
Adult COVID 19 symptomatic patients N = 1200 |
Total: 399 ACEi: 260 ARB: 147 |
Non-ACEi/ARB: 801 |
68 43% |
HTN: 54% DM: 35% CKD: 17% HF: 9% |
Age, sex, hypertension, diabetes mellitus, chronic kidney disease, ischaemic heart disease, heart failure |
| Chen 2020 | Retrospective cohort study | Wuhan, China | Patients with hypertension and diabetes admitted in the hospital for symptomatic COVID-19 infection N = 71 |
Total: 31 ACEi: NR ARB: NR |
Non-ACEi/ARB: 39 | 67 NR |
HTN: 100% DM: 100% |
– |
| Chodik 2020 | Cross sectional Cohort | Tel Aviv, Israel | individuals tested for SARS-COV-2 (RT-PCR) N = 1317 positive N = 13203 negative |
Total: 991 ARB 603 ACEI 388 |
Non-ACEi/ARB: 13,529 | 41 COVID-19+ 37 COVID-19– 40% COVID-19 + / 46% COVID-19 - |
HTN: 14% COVID-19+ 11% COVID-19 - DM: 9% COVID-19+ 5% COVID-19 - CKD: 8% COVID-19+ 6% COVID-19 - HF: 0.2% COVID-19+ 0.6% COVID-19 - |
Age, sex, SES, BMI, and co-morbidities |
| Yan, 2020 | Multicentre retrospective case-control study | Zhejiang, China | Case: Consecutive patients presenting to hospital with confirmed diagnosis of Covid-19 infection N = 610 Control: Population-based control group N = 48667 |
COVID-19+ Total: 58 ACEi: 5 ARB: 53 |
COVID.19 - Total: 8040 ACEi: 555 ARB: 7485 |
49 49% |
HTN: 22% DM: 10% CVD/cerebrovascular disease: 3% |
Age, sex, BMI |
| Felice 2020 | Single-centre retrospective cohort study | Treviso, Italy | Symptomatic COVID-19 hypertensive patients presenting to the emergency department N = 133 |
Total: 82 ACEI: 40 ARB: 42 |
Non-ACEi/ARB: 51 |
73 35% |
HTN: 100% DM: 26% HF: 24% |
– |
| Feng 2020 | Multi-center retrospective cohort study | Wuhan, Shangai, Tongling China |
Subgroup of hypertensive COVID 19 symptomatic patients admitted in 3 hospitals N = 113 |
Total: 33 ACEi: NR ARB: NR |
Non-ACEi/ARB: 62 | 53 45% |
HTN: 100% | – |
| Gao 2020 | Single-centre retrospective cohort study | Wuhan, China | Subgroup of hypertensive COVID 19 symptomatic patients admitted in the hospital N = 710 |
Total: 183 ACEi: NR ARB: NR |
Non-ACEi/ARB: 527 | 64 48% |
HTN: 100% DM: 28% HF: 3% CKD: 2% MI: 1% |
Propensity-matched score for mortality Age, sex, medical history of diabetes, insulin-treated diabetes, myocardial infarction, PCI/CABG, renal failure, stroke, heart failure, and COPD |
| Hu 2020 | Retrospective single-centre cohort | Zhejiang, China |
Subgroup of hypertensive COVID 19 symptomatic patients admitted in the hospital N = 149 |
Total: 65 ACEi: NR ARB: NR |
Non-ACEi/ARB: 84 | 57 41% |
HTN 100% DM: 20% CKD: 4% |
– |
| Huang 2020 | Retrospective single-centre cohort | Wuhan, China | Hypertensive COVID 19 symptomatic patients admitted in the hospital N = 50 |
Total: 20 ACEi: NR ARB: NR |
Non-ACEi/ARB: 30 |
62 45% |
HTN: 100% DM: 8% CAD: 2% |
– |
| Imam 2020 | Retrospective multicentre cohort | Detroit, USA | COVID-19 symptomatic patients N = 1305 |
Total: 565 ACEi: NR ARB: NR |
Non-ACEi/ARB: 740 | 61 46% |
HTN: 56% DM: 30% HF: 6% Vascular Disease: 16% |
Age, comorbidities, NSAID, ACEi/ARB |
| Jung 2020 | Cohort study | Seoul, Korea | Adult COVID 19 patients N = 5179 |
Total: 762 ACEI: 32 ARB: 730 |
Non-ACEi/ARB: 1577 |
45 56% |
HTN: 22% DM: 17% HF: 4% CAD: 1% CKD: 5% |
Age, sex, Charlson Comorbidity Index, immunosuppression, and hospital type. |
| Li 2020 | Retrospective, single-center cohort | Wuhan, China | Hypertensive COVID 19 symptomatic hospitalized patients N = 362 |
Total: 115 ACEi: NR ARB: NR |
Non-ACEI/ARB: 247 | 66 41-51% |
HTN: 100% DM 35% Cerebrovascular disease: 23% CHD: 18% HF 3% |
– |
| Mehra, 2020 | Cohort/Nested case-control | 169 hospitals in Asia, Europe, and North America |
Hospitalized patients from Surgical Outcomes Collaborative (Surgisphere), an international registry N = 8910 |
Total: 1326 ACEi: 770 ARB: 556 |
Non-ACEi/ARB: 7584 | 49 40% |
HTN: 26% CAD: 11% DM: 14% HF: 2% Dyslipidemia: 31% COPD: 3% |
Age, sex, hypertension |
| Mehta, 2020 | Retrospective cohort study | Ohio and Florida, USA | Patients tested for COVID-19 N = 18472 N positive = 1735 N negative = 16737 | Total: 2285 ACEi: 1322 ARB: 982 |
Non-ACEi/ARB: 16187 |
49 60% |
HTN: 93% DM: 46% CAD: 22% HF: 17% COPD: 14% |
Propensity score: Age, sex, and presence of hypertension, diabetes, coronary artery disease, heart failure, and COPD |
| Meng, 2020 | Retrospective single center case control | Shenzhen, China | Hospitalized patients with COVID-19 and receiving anti-hypertensive therapy N = 42 |
Total: 17 ACEi: NR ARB: NR |
Non-ACEi/ARB: 25 | 65 43% |
HTN: 100% DM: 24% ACEi/ARB 8% Non-ACEi/ARB CHD: 35% ACEi/ARB 8% Non-ACEi/ARB |
– |
| Million, 2020 | Retrospective cohort study | Marseille, France | COVID-19 positive tested patients N = 1061 |
ARB: 40 | Non-ARB: 1021 | 44 54% |
HTN: 14% DM: 7% CAD: 4% Obesity: 6% Chronic Respiratory Disease: 11% |
Age, comedications, COVID-19 severity score |
| Montastruc 2020 | Retrospective cohort study | Toulouse, France | Adult patients positive for COVID-19 admitted in the intensive care unit N = 96 |
Total: 35 ACEI: 12 ARB: 23 |
Non-ACEi/ARB: 61 | 63 21% |
HTN: 45% DM: 28% CKD: 10% Arrythmia: 6% |
– |
| Peng 2020 | Retrospective cohort study | Wuhan, China | Hospitalized COVID-19 patients with Cardiovascular disease N = 112 |
Total: 22 ACEi: NR ARB: NR |
Non-ACEi/ARB: 90 | 61 53% |
DM: 33% HTN: 82% |
– |
| Reynolds 2020 | Retrospective cohort study | New York, USA | Patients tested for COVID-19 N = 12594 N positive = 5894 N negative = 6700 | Risk of infection (PSM): Total 1909 ACEi: 1137 ARB: 1044 Risk of severe infection (PSM): Total 1110 ACEi: 627 ARB: 664 |
Risk of infection (PSM): Non-ACEi/ARB: 4344 Risk of severe infection (PSM): Non-ACEi/ARB: 2453 |
49 59% |
HTN: 35% DM: 18% HF: 6% MI: 4% CKD: 18% COPD: 15% Current smoker: 5% Former smoker: 18% |
Age; sex; race; ethnic group; body-mass index; smoking history; history of hypertension, myocardial infarction, heart failure, diabetes, chronic kidney disease, and obstructive lung disease (e.g., asthma and obstructive pulmonary diseases) |
| Tan, 2020 | Retrospective cohort study | Wuhan, China | Subgroup of symptomatic COVID-19 patients with hypertension N = 100 |
Total: 31 ACEi: NR ARB: NR |
Non-ACEi/ARB: 69 | 67 NR |
HTN: 100% DM: 26% ACEi/ARB 29% Non-ACEi/ARB GI: 19% ACEi/ARB 25% Non-ACEi/ARB CKD: 7% ACEi/ARB 13% Non-ACEi/ARB CHD: 10% ACEi/ARB 16% Non-ACEi/ARB COPD: 7% ACEi/ARB 10% Non-ACEi/ARB Tumor: 3% ACEi/ARB 6% Non-ACEi/ARB |
– |
| Tedeschi, 2020 | Prospective cohort study | Bologna, Italy |
Hypertensive adult COVID 19 patients hospitalized N = 311 |
Total: 175 ACEI: 99 ARB: 76 |
Non-ACEi/ARB: 136 | 76 28% |
HTN: 100% CAD: 42% DM: 24% |
Age, gender, presence of CV comorbidities and COPD |
| Yang, 2020 | Retrospective, single-center study | Wuhan, China |
Subgroup of hypertensive patients with COVID-19 hospitalized N = 126 |
Total: 43 ACEi: NR ARB: NR |
Non-ACEi/ARB: 83 | Median 67 51% |
HTN: 100% DM: 30% Respiratory disease: 5% Kidney disease: 3% Hepatic disease: 6% Cardiopathy: 18% Neurological disease: 8% |
– |
| Zhang, 2020 | Retrospective cohort/nested case-control | Hubei, China | Hypertensive patients with COVID-19 hospitalized N = 522 matching 1:2 |
Total: 174 ACEi: NR ARB: NR |
Non-ACEi/ARB: 348 | median 64 47% |
HTN: 100% DM: 24% CAD: 12% CKD 3% CVD: 3% COPD: 1% |
Age, gender, fever, cough, dyspnea, comorbidities (diabetes, coronary heart disease, and chronic renal disease), CT-diagnosed bilateral lung lesions, and incidence of increased CRP and creatinine. |
| Zhou 2020 | Retrospective, single-center study | Wuhan, China |
Subgroup of hypertensive patients with symptomatic COVID-19 hospitalized N = 36 |
Total: 15 ACEi: NR ARB: NR |
Non-ACEi/ARB: 21 | 65 47% |
HTN:100% DM: 25% CVD: 19% |
Age, sex, hospitalization time, time from onset to hospital admission, and whether to take ACEi or ARB |
| UNPUBLISHED | ||||||||
| Rossi 2020 | Population-based prospective cohort study on archive data | Reggio Emilia, Italy |
COVID-19 symptomatic patients N = 2653 |
Total: 818 ACEi: 450 ARB: 368 |
Non-ACEi/ARB: 1835 | 63 50% |
HTN: 18% DM: 12% MI: 7% HF: 6% CKD: 3% COPD: 5% Vascular disease: 3% |
Age, sex and analysis restricted to subjects with ischemic heart disease, hypertension, or heart failure |
| Ip 2020 | Retrospective, Cohort, multicenter study | New Jersey, USA | Subgroup of hypertensive COVID 19 symptomatic hospitalized patients N = 1584 |
Total: 1231 ACEi: 688 ARB: 543 |
Non-ACEi/ARB: NR | NR | HTN: 100% | – |
| Liu 2020 | Multicentre retrospective cohort study | Shenzhen, Wuhan, and Beijing, China | Hypertensive COVID 19 symptomatic hospitalized elderly pts (greater than65 years-old) N = 78 |
Total: 12 ACEi: 2 ARB: 10 |
Non-ACEi/ARB: 8 | NR | HTN 100% | Gender |
| Rentsch 2020 | Retrospective cohort study | Connecticut, USA | Patients from National Veterans Affairs Healthcare System tested for COVID-19 N = 3789 | Total: 1532 ACEi: NR ARB: NR |
Non-ACEi/ARB: 2257 | 66 10% |
HTN: 65% DM: 38% Vascular disease: 29% COPD: 26% Alcohol use disorder: 14% |
Age, sex, race, medication, residence type, comorbidities |
| Zeng 2020 | Retrospective, single-center study | Wuhan, China |
Subgroup of hypertensive patients with clinically confirmed COVID-19 hospitalized N = 75 |
Total: 28 ACEi: NR ARB: NR |
Non-ACEi/ARB: 47 | 67 53% |
HTN: 100% DM: 31% CVD: 21% CKD: 5% |
– |
| Khera 2020 | Retrospective Cohort | Connecticut, USA | Hypertension patients hospitalized for COVID-19 N = 7933 | Total: 4587 ACEi: 2361 ARB: 2226 |
Non-ACEI/ARB: 3346 | Median 69 53% |
HTN 100% DM: 68% MI 4% HF 14% |
Propensity score: age, gender, race, insurance type, conditions that may lead to selective use of ACE inhibitors and ARBs each of the comorbidities in the Charlson Comorbidity Index, and the number of anti-hypertensive agents used for the patient |
*with a diagnosis of ischaemic heart disease (ICD9CM at discharge 410–414), cerebrovascular disease (430–438), or heart failure (428), and persons registered in the regional register of persons with diabetes.
Legend: RT-CPR reverse transcriptase-polymerase chain reaction; ACEi Angiotensin-converting-enzyme inhibitors; ARB angiotensin receptor blocker; RAAS renin-angiotensin-aldosterone system; SES socioeconomic status; BMI body mass index; HTN hypertension; CAD coronary artery disease; HF heart failure; DM diabetes mellitus; CKD chronic kidney disease; MI myocardial infarction; COPD Chronic obstructive pulmonary disease; CHD chronic heart disease; PCI percutaneous coronary intervention; PSM: Propensity-score matching CABG coronary artery bypass graft; NSAID Nonsteroidal anti-inflammatory drugs; GI gastrointestinal; CT computed tomography; CRP c-reactive protein; pts patients.