Table 1.
Associations between statins and COVID-19 outcomes, and clinical trials regarding statin use in COVID-19.
| References | Type of study | Study cohort | Key findings | |
|---|---|---|---|---|
| Associations between statins and COVID-19 outcomes | ||||
| Song et al. (27) | Retrospective study | 249 adult patients hospitalized with COVID-19 in Rhode Island, USA | After adjusting for age, sex, race, cardiovascular disease, chronic pulmonary disease, diabetes, and obesity, statin use was significantly associated with decreased risk for IMV [aOR = 0.45, (95% CI: 0.20–0.99)]. | |
| Vahedian-Azimi et al. (28) | Meta-analysis | 32,715 patients in 24 studies | Statin use is associated with significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I2 = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I2 = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I2 = 89.0%). Death was reduced further by in-hospital application of stains (OR = 0.40, 95% CI: 0.22–0.73, n = 3; I2 = 82.5%), compared with pre-hospital use (OR = 0.77, 95% CI: 0.60–0.98, n = 18; I2 = 81.8%). |
|
| Zhang et al. (29) | Retrospective study | 13,981 cases of confirmed COVID-19 admitted in 21 hospitals from Hubei Province, China | The risk for 28-day all-cause mortality was 5.2 and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted HR of 0.58; the use of statins in hospitalized subjects with COVID-19 was associated with a lower risk of all-cause mortality and a favorable recovery profile. | |
| Lee et al. (30) | Nested case-control study | 10,448 COVID-19 patients who were hospitalized in Korea | Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins [aHR, 0.637 (95% CI, 0.425–0.953); P = 0.0283]. Statin use is correlated with lower mortality in COVID-19 patients. | |
| Memel et al. (31) | Cohort study | 1,179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a BMI ≥30 | Inpatient statin use reduced the hazard of death (HR, 0.566; P = 0.008). This association held among patients who did and those did not use statins before hospitalization [HR, 0.270 (P = 0.003) and 0.493 (P = 0.04), respectively]. Statin use was associated with improved time to death for patients aged >65 years but not for those ≤ 65 years old. Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. |
|
| Choi et al. (32) | Retrospective study | 5,375 COVID-19 patients admitted to Mount Sinai Health System hospitals in New York | Compared to non-statin users, both low-to-moderate-intensity (aHR 0.62, 95% CI 0.51–0.76) and high-intensity statin users (aHR 0.53, 95% CI 0.43–0.65) had a reduced risk of death. Subgroup analysis of 723 coronary artery disease patients showed decreased mortality among high-intensity statin users compared to non-users (aHR 0.51, 95% CI 0.36–0.71). Statin use in patients hospitalized with COVID-19 was associated with a reduced in-hospital mortality. The protective effect of statin was greater in those with coronary artery disease. |
|
| Rodriguez-Nava et al. (33) | Retrospective cohort study | 87 adult patients with COVID-19 admitted to community hospital ICU in Evanston, IL, USA | In the multivariable Cox proportional hazards regression model, atorvastatin non-users had a 73% chance of faster progression to death compared with atorvastatin users (when probability = HR/HR + 1). | |
| Daniels et al. (34) | Retrospective single-center study | 170 hospitalized patients with COVID-19 and 5,281 COVID-negative subjects at University of California San Diego Health | Statin use prior to admission was associated with reduced risk of severe COVID-19 (aOR 0.29, 95% CI 0.11–0.71, P < 0.01) and faster time to recovery among those without severe disease (aHR for recovery 2.69, 95% CI 1.36–5.33, P < 0.01). The association between statin use and severe disease was smaller in the COVID-negative cohort (P for interaction = 0.07). |
|
| Rossi et al. (35) | Follow-up study | 71 consecutive patients with a pre-existing chronic cardiovascular disease, who become ill from COVID-19 | Among 42 statin users, 16/42 (38.1%) took a hydrophilic statin (rosuvastatin in 14 patients and pravastatin in 2), while 26/42 (61.9%) a lipophilic statin (atorvastatin in 22 patients, and simvastatin in 4). The group of lipophilic statins demonstrated a significant reduction in mortality respect both patients who do not take statins, and patients who assumed hydrophilic statins. | |
| Saeed et al. (36) | Observational study | 4,252 patients (65 ± 16 years old; 47% female) were admitted with COVID-19, 37% (n = 1,570) were Hispanic | Patients with diabetes mellitus on a statin (n = 983) reduced cumulative in-hospital mortality (24 vs. 39%; P < 0.01) than those not on a statin (n = 1,283). Statin use in people with diabetes was associated with a reduced risk of in-hospital mortality during COVID-19. No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20 vs. 21%; P = 0.82). |
|
| De Spiegeleer et al. (37) | Retrospective study | 154 COVID-19 diagnosed residents aged 86 ± 7 years in 2 Belgian nursing homes | Statin intake is associated with the absence of symptoms during COVID-19 (OR 2.91; 95% CI 1.27–6.71), which remained statistically significant after adjusting for covariates (aOR 2.65; 95% CI 1.13–6.68). In conclusion, statin intake in older, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. | |
| Lala et al. (38) | Retrospective study | 2,736 patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City | Statins have a protective effect and were associated with improved survival (HR 0.57, 95% CI 0.47–0.69). | |
| Gupta et al. (39) | Retrospective study | 2,626 patients admitted with COVID-19, of whom 951 (36.2%) were antecedent statin users. | Among 1,296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of in-hospital mortality within 30 days in the propensity-matched cohort (OR 0.47, 95% CI 0.36–0.62, P < 0.001). | |
| Byttebier et al. (40) | Retrospective observational case-control study | 959 COVID-19 patients admitted consecutively to four Belgian hospitals | Treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17–0.69). In-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives. | |
| Ayeh et al. (41) | Retrospective study | 4,447 patients hospitalized at the Johns Hopkins Hospital and affiliated hospitals with COVID-19, 594 (13.4%) were exposed to statins on admission. | The average treatment effect of statin use on COVID-19-related mortality was RR = 1.00 (95% CI: 0.99–1.01, P = 0.928), while its effect on severe COVID-19 infection was RR = 1.18 (95% CI: 1.11–1.27, P < 0.001). | |
| Statin use was not associated with altered mortality, but with an 18% increased risk of severe COVID-19 infection. | ||||
| Kollias et al. (42) | Meta-analysis | 41,807 patients, 14% with statin use | Statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients. | |
| Lee et al. (43) | Two independent population-based nationwide cohort studies | 214,207 patients older than 20 years who underwent tests for SARS-CoV-2 infection in South Korea | Statin users were associated with a decreased likelihood of severe clinical outcomes [statin users, 3.98% (32/804); non-users, 5.40% (85/1,573); aRR 0.62; 95% CI 0.41–0.91] and length of hospital stay (statin users, 23.8 days; non-users, 26.3 days; adjusted mean difference −2.87; 95% CI −5.68 to −0.93) than non-users. | |
| Prior statin use is related to a decreased risk of worsening clinical outcomes of COVID-19 and length of hospital stay but not to that of SARS-CoV-2 infection. | ||||
| Kow et al. (44) | Meta-analysis | 8,990 COVID-19 patients in 4 studies | The pooled analysis revealed a significantly reduced hazard for fatal or severe disease with the use of statins (Pooled HR = 0.70; 95% CI 0.53–0.94) compared to non-use of statins in COVID-19 patients. | |
| Tan et al. (45) | Retrospective study | 717 patients admitted to a tertiary center in Singapore for COVID-19 infection. | 156 (21.8%) patients had dyslipidaemia and 97% of these were on statins. Logistic treatment models showed a lower chance of ICU admission for statin users when compared to non-statin users (Average treatment effect on statin (ATET): Coeff (risk difference): −0.12 (−0.23, −0.01); P = 0.028). Statin use was independently associated with lower ICU admission. | |
| Study Title | Status | Locations | Summary | Key results |
| COVID-19 related clinical trials of statins | ||||
| Intermediate-dose vs. standard prophylactic anticoagulation and statin vs. placebo in ICU patients with COVID-19 (NCT04486508) | Completed | Masih Daneshvari Hospital, Tehran, Iran, Islamic Republic of Iran | This study investigates the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients (Actual Enrollment: 600 participants) with COVID-19 using a 2 × 2 factorial design. | In adults with COVID-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all-cause mortality compared with placebo. The treatment was safe (46) |
| Effectiveness and safety of medical treatment for SARS-CoV-2 (COVID-19) in Colombia (NCT04359095) | Completed | 6 hospitals in Colombia including Clinica santa Maria del lago, Clínica Reina Sofía, Fundacion Cardio Infantil, etc. | The study assesses the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients. Six hundred and forty-nine patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The primary endpoint was 28-day all-cause mortality. | The combined use of emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin reduces the risk of 28-day mortality and the need for IMV in hospitalized patients with COVID-19 (47). |
| The impact of statin therapy in the COVID-19 patients (NCT05238402) | Completed | Deniz Demirci Antalya, Turkey | The study is retrospective single-center review of covid-19 patients (actual Enrollment: 707 participants). The study population was divided into patients who received a statin vs. those who did not receive a statin before the hospitalization. The primary outcome was in-hospital mortality during the follow-up period. | No results posted |
| Statin therapy and COVID-19 infection (NCT04407273) | Completed | Facultat de Medicina i Ciències de la Salut de Reus, Reus, Tarragona, Spain | This is a retrospective observational multicenter study. The SARS-CoV-2 severity of 2,159 COVID-19-infected patients with statin therapy was classified into 9 grades. Primary outcome is the WHO SARS-CoV-2 scale of severity (9 grades) achieved by COVID-19 patients, admitted in the hospital, with and without background statin therapy comparable in age and gender distribution. | No results posted |
| Randomized, embedded, multifactorial adaptive platform trial for community- acquired pneumonia (NCT02735707) | Recruiting | 322 hospitals worldwide | The purpose of this study is to evaluate the effect of about 50 interventions, including statin use, to improve outcome of patients admitted to ICU with community-acquired pneumonia including COVID-19. | No results posted |
| Colchicine/statins for the prevention of COVID-19 complications (COLSTAT) trial (NCT04472611) | Recruiting | 4 hospitals in United States including Bridgeport Hospital, Greenwich Hospital, Yale New Haven Hosptial System, Lawrence and Memorial Hospital | This is a randomized open-label study of the safety and efficacy of the combination of colchicine and Rosuvastatin in addition to standard of care (SOC) compared to SOC alone in hospitalized patients with SARS-CoV-2 (Estimated Enrollment: 466 participants). The primary endpoint is the 30-day composite of progression to severe COVID-19 disease. | No results posted |
| Managing endothelial dysfunction in critically ill COVID-19 patients at LAUMCRH (NCT04813471) | Recruiting | LAUMCRH Beirut, Lebanon | The study seeks to target endothelial dysfunction in critically ill patients with COVID-19 by giving them an endothelial protocol (L-arginine, Folic Acid, Statin, Nicorandil, Vitamin B complex) and monitor clinical outcome in those patients. | No results posted |
| Atorvastatin as adjunctive therapy in COVID-19 (NCT04380402) | Recruiting | Mount Auburn Hospital Cambridge, Massachusetts, United States | This study assesses whether adjunctive therapy of COVID-19 with atorvastatin reduces the deterioration in hospitalized patients and improves clinical outcome. | No results posted |
| Helping alleviate the longer-term consequences of COVID-19 (HEAL-COVID) (NCT04801940) | Recruiting | Addenbrookes Hospital, Cambridge, United Kingdom | HEAL-COVID aims to evaluate the impact of treatments on longer-term morbidity, mortality, re-hospitalization, symptom burden and quality of life associated with COVID-19. The first two treatment arms are Apixaban and Atorvastatin. | No results posted |
| Combination therapies to reduce carriage of SARS-CoV-2 and improve outcome of COVID-19 in ivory coast: a phase randomized IIb trial (NCT04466241) | Recruiting | 2 hospitals in Côte D'Ivoire including Service des Maladies Infectieuses et Tropicales, Centre Hospitalier et Universitaire (CHU) and Treichville Abidjan, Côte D'Ivoire Center de Traitement des Maladies Infectieuses (CTMI) | This study proposes to study whether the combination of two drugs (These drugs include the LPV/r already in use in Côte d'Ivoire as well as an antihypertensive drug—telmisartan, and atorvastatin) is more effective than taking a single drug on reducing the viral load in the respiratory tract but also on reducing inflammation. | No results posted |
| Statin treatment for COVID-19 to optimize neurological recovery (NCT04904536) | Not yet recruiting | The George Institute for Global Health Sydney, New South Wales, Australia | This trial was designed to study whether atorvastatin treatment (40 mg/day) over 18 months can improve neurocognitive function in adults with long COVID neurological symptoms. | No results posted |
| A study of anticoagulation treatment patterns and outcomes of participants hospitalized with coronavirus disease 2019 (COVID-19) in Japan (NCT04828772) | Active, not recruiting | Medical Data Vision, Tokyo, Japan | This study plans to assess the benefits and harms of anticoagulants (including statins) vs. active comparator, placebo or no intervention in people hospitalized with COVID-19. | Compared with no treatment, anticoagulants may reduce all-cause mortality but the evidence comes from non-randomized studies and is very uncertain (48). |
| Managing endothelial dysfunction in COVID-19: a randomized controlled trial at LAUMC (NCT04631536) | Active, not recruiting | LAUMCRH Beirut, Lebanon | This trial will examine the potential therapeutic effect of a regiment composed of several medications including atorvastatin as adjunct to mainstream management, to further knowledge in treating COVID-19. | No results posted |
| Atorvastatin for reduction of 28-day mortality in COVID-19: RCT (NCT04952350) | Active, not recruiting | Mansoura University Hospitals Mansoura, Aldakahlia, Egypt | This randomized placebo-controlled double-blinded clinical trial aims to test the efficacy of administering atorvastatin 40 mg to hospitalized COVID-19 patients for 28 days on the all-cause 28-day mortality. | No results posted |
| Study of ruxolitinib plus simvastatin in the prevention and treatment of respiratory failure of COVID-19 (NCT04348695) | Unknown | Hospital Universitario Madrid Sanchinarro, Madrid, Spain | This project examines whether the combined use of ruxolitinib with simvastatin show a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect. | No results posted |
| Preventing cardiac complication of COVID-19 disease with early acute coronary syndrome therapy: a randomized controlled trial (NCT04333407) | Unknown | Charing Cross Hospital, London, United Kingdom | The trial plans to assess all-cause mortality 30 days after admission in COVID-19 patients (Estimated Enrollment: 3,170 participants) treated with different cardioprotective drugs, including Aspirin 75 mg, Clopidogrel 75 mg, Rivaroxaban 2.5 MG, Atorvastatin 40 mg, Omeprazole 20 mg. | No results posted |
| Coronavirus response—active support for hospitalized COVID-19 patients (NCT04343001) | Withdrawn | University College Hospital Ibadan, Oyo, Nigeria, and Shifa Tameer-e-Millat University, Rawalpindi, Pakistan | This project aims to evaluate the effect of aspirin (150 mg once daily), losartan (100 mg once daily), and simvastatin (80 mg once daily) in patients with COVID-19 infection. | No results posted |
Data was acquired as of April 16, 2022. aHR, adjusted hazard ratio (HR); aOR, adjusted odds ratio (OR); BMI, body mass index; CI, confidence interval; ICU, intense care unit; IMV, invasive mechanical ventilation; I2, I-squared statistics indicating between-study heterogeneity; RR, risk ratio.